Job/Unit: O21064
/KAP1
Date: 05-09-12 18:15:54
Pages: 9
New Reagent for Oxidative Iodination of Arenes
4-Hydroxy-3,5-diiodoacetophenone (5n): Reaction of 4-hydroxy- CDCl3): δ = 9.83 (s, 1 H), 8.31 (d, J = 2.0 Hz, 1 H), 7.86 (dd, J =
acetophenone (4n) (27.2 mg, 0.2 mmol), iodine (55.9 mg,
0.22 mmol) and potassium 4-iodylbenzenesulfonate (2) (42.5 mg,
0.12 mmol) in MeCN (0.5 mL) and aqueous H2SO4 (5%, 0.5 mL)
according to the general procedure (diiodination Method A at
room temp.), afforded 68.3 mg (88%) of product, isolated as a
white crystalline solid, m.p. 159–160 °C (from MeOH/H2O, 1:1)
(ref.[12] m.p. 158–160 °C). HRMS (ESI): calcd. for C8H5I2O2 [M –
8.5, 2.0 Hz, 1 H), 6.93 (d, J = 8.5 Hz, 1 H), 3.98 (s, 3 H, OCH3)
ppm.
Iodination Procedure with Recovery of Potassium 4-Iodylbenzene-
sulfonate (2). Preparation of 4-Bromo-2-iodoanisole (5h): To a mix-
ture of 4-bromoanisole (4h) (468 mg, 2.5 mmol), iodine (350 mg,
1.38 mmol) and potassium 4-iodylbenzenesulfonate (2) (347 mg,
0.98 mmol) in MeCN (3.0 mL) was added aqueous H2SO4 (5%,
3.0 mL), and the reaction mixture was stirred at 80 °C for 12 h; the
reaction was monitored by TLC and GC–MS. The reaction mixture
was then cooled to room temp. and extracted with hexanes
(6.0 mL). Concentration of the hexanes layer gave 634 mg (81%)
of 4-bromo-2-iodoanisole (5h). Oxone (1.2 g) was added to the
water layer after extraction. This mixture was stirred at 60 °C for
2 h, then cooled to 5 °C, and the resulting precipitate was filtered,
washed with water (3ϫ 1.0 mL), and dried to afford 320 mg (92%
recovery) of potassium 4-iodylbenzenesulfonate (2).
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H]– 386.8379, found 386.8378. H NMR (200 MHz, CD3OD): δ =
8.35 (s, 2 H), 2.54 (s, 3 H, CH3) ppm.
2,5-Diiodo-1,4-dimethylbenzene (5o): Reaction of 1,4-dimethylbenz-
ene (4o) (21.2 mg, 0.2 mmol), iodine (55.9 mg, 0.22 mmol) and
potassium 4-iodylbenzenesulfonate (2) (42.5 mg, 0.12 mmol) in
MeCN (0.5 mL) and aqueous H2SO4 (5%, 0.5 mL) according to
the general procedure (diiodination Method A at 65 °C), afforded
65.8 mg (92%) of product 5o, isolated as white needle-shaped crys-
tals, m.p. 102.5–103.5 °C (ref.[19] m.p. 103–104 °C). 1H NMR
(500 MHz, CDCl3): δ = 7.65 (s, 2 H), 2.34 (s, 6 H, CH3) ppm.
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra for key products.
2,4-Diiodo-1,3,5-trimethylbenzene (5p): Reaction of 1,3,5-trimeth-
ylbenzene (4d) (24 mg, 0.2 mmol), iodine (55.9 mg, 0.22 mmol) and
potassium 4-iodylbenzenesulfonate (2) (42.5 mg, 0.12 mmol) in
MeCN (0.5 mL) and aqueous H2SO4 (5%, 0.5 mL) according to
the general procedure (diiodination Method A at 65 °C), afforded
73.6 mg (99%) of product 5p, isolated as white needle-shaped crys-
tals, m.p. 80–81.5 °C (ref.[19] m.p. 82 °C). 1H NMR (500 MHz,
CDCl3): δ = 7.00 (s, 1 H), 2.93 (s, 3 H, CH3), 2.42 (s, 6 H, CH3)
ppm.
Acknowledgments
This work was supported by a research grant from the National
Science Foundation (CHE-1009038). M. S. Y. and V. V. Z. are also
thankful to the Government of Russia for support of their coopera-
tive research program (FCP GK11.519.11.5010, Zayavka 2011-1.9-
519-024-070 and Russian Foundation for Basic Research No. 12-
03-00978-a).
4-Iodo-1,2-dimethoxybenzene (5q): Reaction of 1,2-dimethoxybenz-
ene (4q) (138 mg, 1.0 mmol), iodine (127 mg, 0.5 mmol) and potas-
sium 4-iodylbenzenesulfonate (2) (106 mg, 0.3 mmol) in acetic acid
(5 mL) according to the general procedure (monoiodination
Method C at 80 °C), afforded 253 mg (96%) of product, isolated
as an oil that can be crystallized in a refrigerator. 1H NMR
(500 MHz, CDCl3): δ = 7.22 (dd, J = 8.5 and 2.0 Hz, 1 H), 7.11
(d, J = 2.0 Hz, 1 H), 6.61 (d, J = 8.5 Hz, 1 H), 3.85 (s, 3 H, 2-
OCH3), 3.84 (s, 3 H, 1-OCH3) ppm.[20]
[1] For books and selected reviews on hypervalent iodine chemis-
try, see: a) A. Varvoglis, Hypervalent Iodine in Organic Synthe-
sis Academic Press, London, 1997; b) Hypervalent Iodine
Chemistry (Ed.: T. Wirth), Springer-Verlag, Berlin, 2003; c)
G. F. Koser, Adv. Heterocycl. Chem. 2004, 86, 225–292; d)
R. M. Moriarty, J. Org. Chem. 2005, 70, 2893–2903; e) P. Dau-
ban, R. H. Dodd, Synlett 2003, 1571–1586; f) M. A. Ciufolini,
N. A. Braun, S. Canesi, M. Ousmer, J. Chang, D. Chai, Synthe-
sis 2007, 3759–3772; g) V. V. Zhdankin, Sci. Synthesis 2007, 31,
Ch. 31.4.1, 161–234; h) M. Ochiai, K. Miyamoto, Eur. J. Org.
Chem. 2008, 4229–4239; i) T. Dohi, Y. Kita, Chem. Commun.
2009, 2073–2085; j) S. Quideau, L. Pouysegu, D. Deffieux, Syn-
lett 2008, 467–495; k) V. V. Zhdankin, ARKIVOC 2009, (i), 1–
62; l) M. Uyanik, K. Ishihara, Chem. Commun. 2009, 2086–
2099; m) M. Uyanik, K. Ishihara, Aldrichim. Acta 2010, 43,
83–91; n) E. A. Merritt, B. Olofsson, Synthesis 2011, 517–538;
o) J. P. Brand, D. F. Gonzalez, S. Nicolai, J. Waser, Chem. Com-
mun. 2011, 47, 102–115; p) E. A. Merritt, B. Olofsson, Angew.
Chem. 2009, 121, 9214; Angew. Chem. Int. Ed. 2009, 48, 9052–
9070; q) M. Ngatimin, D. W. Lupton, Aust. J. Chem. 2010, 63,
653–658; r) S. Quideau, T. Wirth, Tetrahedron 2010, 66, 5737–
5738; s) M. S. Yusubov, V. V. Zhdankin, Mendeleev Commun.
2010, 20, 185–191; t) J. L. F. Silva, B. Olofsson, Nat. Prod. Rep.
2011, 28, 1722–1754; u) M. S. Yusubov, A. V. Maskaev, V. V.
Zhdankin, ARKIVOC 2011, (i), 370–409; v) C. D. Turner,
M. A. Ciufolini, ARKIVOC 2011, (i), 410–428; w) M. S. Yusu-
bov, V. V. Zhdankin, Curr. Org. Synth. 2012, 9, 247–272.
[2] For reviews on hypervalent iodine(V) reagents, see: a) T. Wirth,
Angew. Chem. 2001, 113, 2893; Angew. Chem. Int. Ed. 2001,
40, 2812–2814; b) U. Ladziata, V. V. Zhdankin, ARKIVOC
2006, (ix), 26–58; c) U. Ladziata, V. V. Zhdankin, Synlett 2007,
527–537; d) V. Satam, A. Harad, R. Rajule, H. Pati, Tetrahe-
dron 2010, 66, 7659–7706; e) A. Duschek, S. F. Kirsch, Angew.
Chem. Int. Ed. 2011, 50, 1524–1552; f) V. V. Zhdankin, J. Org.
Chem. 2011, 76, 1185–1197.
4-Iodo-1,3-dimethoxybenzene (5r): Reaction of 1,3-dimethoxybenz-
ene (4r) (138 mg, 1.0 mmol), iodine (127 mg, 0.5 mmol) and potas-
sium 4-iodylbenzenesulfonate (2) (106 mg, 0.3 mmol) in acetic acid
(5 mL) according to the general procedure (monoiodination
Method C at 80 °C), afforded 258 mg (98%) of product, isolated
as an oil that can be crystallized in a refrigerator. 1H NMR
(500 MHz, CDCl3): δ = 7.61 (d, J = 8.5 Hz, 1 H), 6.43 (d, J =
2.5 Hz, 1 H), 6.32 (dd, J = 8.5, 2.5 Hz, 1 H), 3.85 (s, 3 H, 3-OCH3),
3.80 (s, 3 H, 1-OCH3) ppm.[21]
2-Iodo-1,4-dimethoxybenzene (5s): Reaction of 1,4-dimethoxybenz-
ene (4s) (138 mg, 1.0 mmol), iodine (127 mg, 0.5 mmol) and potas-
sium 4-iodylbenzenesulfonate (2) (106 mg, 0.3 mmol) in acetic acid
(5 mL) according to the general procedure (monoiodination
Method C at 80 °C), afforded 237 mg (90%) of product 5s, isolated
as a pink oil that can be crystallized in a refrigerator. 1H NMR
(500 MHz, CDCl3): δ = 7.34 (d, J = 3.0 Hz, 1 H), 6.86 (dd, J =
9.0, 3.0 Hz, 1 H), 6.75 (d, J = 9.0 Hz, 1 H), 3.82 (s, 3 H, 4-OCH3),
3.75 (s, 3 H, 1-OCH3) ppm.[22]
3-Iodo-4-methoxybenzaldehyde (5t): Reaction of 4-methoxybenz-
aldehyde (4t) (27.2 mg, 0.2 mmol), iodine (27.9 mg, 0.11 mmol) and
potassium 4-iodylbenzenesulfonate (2) (21 mg, 0.06 mmol) in
MeCN (0.5 mL) and aqueous H2SO4 (5%, 0.5 mL) according to
the general procedure (monoiodination Method A at 65 °C), af-
forded 50.8 mg (97%) of product 5t, isolated as white crystals, m.p.
104–106 °C (ref.[23] m.p. 104.5–106.5 °C). 1H NMR (500 MHz,
[3] IBX can explode violently upon impact or heating above
200 °C; see: a) J. B. Plumb, D. J. Harper, Chem. Eng. News
Eur. J. Org. Chem. 0000, 0–0
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