Synthesis of diiodo- and triiodoanilines by iodination of aniline with potassium dichloroiodate and preparation of 1,3,5-triiodobenzene

Article abstract of DOI:10.1023/B:RUCB.0000030826.76441.af

A new chemoselective procedure was developed for the synthesis of 2,4,6-triiodoaniline and 2,4-diiodoaniline by the reaction of aniline with potassium dichloroiodate in dilute HCl. Subsequent deamination of 2,4,6-triiodoaniline afforded 1,3,5-triiodobenzene in good yield.

Full text of DOI:10.1023/B:RUCB.0000030826.76441.af

Russian Chemical Bulletin, International Edition, Vol. 53, No. 2, pp. 471—473, February, 2004
471
Brief Communications
Synthesis of diiodoꢀ and triiodoanilines by iodination of aniline with
potassium dichloroiodate and preparation of 1,3,5ꢀtriiodobenzene
S. Z. Vatsadze,ꢀ I. D. Titanyuk, A. V. Chernikov, and N. V. Zyk
Department of Chemistry, M. V. Lomonosov Moscow State University,
Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (095) 939 0290. Eꢀmail: SZV@org.chem.msu.ru
A new chemoselective procedure was developed for the synthesis of 2,4,6ꢀtriiodoaniline
and 2,4ꢀdiiodoaniline by the reaction of aniline with potassium dichloroiodate in dilute HCl.
Subsequent deamination of 2,4,6ꢀtriiodoaniline afforded 1,3,5ꢀtriiodobenzene in good yield.
Key words: iodination, diazotization, aniline, potassium dichloroiodate, 2,4,6ꢀtriiodoaniline,
2,4ꢀdiiodoaniline, 1,3,5ꢀtriiodobenzene.
Iodoanilines are of considerable interest in the synꢀ
thesis of polyiodoarenes, which serve as important startꢀ
ing compounds in crossꢀcoupling reactions with alkenes
and alkynes1 known as the Heck and Sonogashira reacꢀ
tions, respectively.
2,4,6ꢀTriiodoaniline (1) is generally prepared by the
reactions of aniline with iodine in the presence of oxiꢀ
dants,2 with ICl vapor,3 or starting from difficultly accesꢀ
sible reagents.4 The preparation of 2,4,6ꢀtriiodoaniline
(1) from aniline by the reactions with Nꢀiodosuccinimide,5
the pyridine—iodine chloride complex,6 or butyl(triꢀ
ethyl)ammonium triiodide can also be mentioned.7 Conꢀ
venient synthetic procedures for the preparation of
2,4ꢀdiiodoaniline (2) are lacking.8
diiodoaniline (2) being selectively prepared depending on
the reaction conditions (Scheme 1).
The reaction of aniline with 2 equiv. of KICl2 in a
highly dilute aqueous HCl afforded 2,4ꢀdiiodoaniline 2,
which precipitated and was not subjected to further iodiꢀ
nation. The use of more concentrated solutions led to a
decrease in the yield of the target product.
The synthesis of triiodide 1 requires 3 equiv. of potasꢀ
sium dichloroiodate and an even more dilute solution of
aniline; otherwise a mixture of compounds 1 and 2 preꢀ
cipitates. This can be attributed to the fact that diiodide 2,
which is formed virtually immediately, remains in soluꢀ
tion due to its low concentration and can further react
with an additional equivalent of the reagent.
We developed a new chemoselective procedure for the
synthesis of iodoanilines 1 and 2 by the reaction of aniline
with potassium dichloroiodate in dilute HCl. Both comꢀ
pounds were prepared in one step, triiodoaniline (1) or
1,3,5ꢀTriiodobenzene (3) can be prepared by the reꢀ
action of 1,3,5ꢀtribromobenzene with potassium iodide
in the presence of iodine,9 by the Hunsdiecker reacꢀ
tion from silver 1,3,5ꢀbenzenetricarboxylate,10 from
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 450—452, February, 2004.
1066ꢀ5285/04/5302ꢀ0471 © 2004 Plenum Publishing Corporation

472
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 2, February, 2004
Vatsadze et al.
Scheme 1
spectively. The chemical shifts are given in the δ scale relative to
HMDS as the internal standard.
The melting points were determined on a Termoelectric 9100
block in an open capillary. All melting points are uncorrected.
2,4ꢀDiiodoaniline (2). Freshly distilled aniline (1 mL,
11 mmol) was dissolved in concentrated HCl (50 mL) and diꢀ
luted with water to 0.5 L. Then KICl2 (5.2 g, 22 mmol) was
added portionwise with vigorous stirring at ≈20 °C, this being
followed by the gradual formation of a grayish precipitate. After
completion of the reaction (3 h), the precipitate was filtered off
and recrystallized from benzene with addition of activated carꢀ
bon. The yield of diiodoaniline 2 was 2.14 g (57%), m.p. 95 °C
(cf. lit. data8: m.p. 95 °C). 1H NMR (CDCl3), δ: 3.74 (br.s, 2 H,
NH2); 6.49 (d, 1 H, C(6)H, J = 8.2 Hz); 7.36 (dd, 1 H, C(5)H,
J1 = 1.0 Hz; J2 = 8.2 Hz); 7.87 (d, 1 H, C(3)H, J = 1 Hz).
2,4,6ꢀTriiodoaniline (1) was prepared analogously to comꢀ
pound 2 with the use of 3 equiv. of KICl2. The mixture of aniline
and HCl was diluted to 0.75 L. The yield of triiodoaniline 1 was
4.51 g (87%), m.p. 185 °C (cf. lit. data2: m.p. 185 °C). 1H NMR
(CDCl3), δ: 4.63 (br.s, 2 H, NH2); 7.85 (s, 2 H, ArH).
i. HCl, 3 equiv. of KICl2, ii. HCl, 2 equiv. of KICl2.
1,3,5ꢀTriiodobenzene (3).13 Finely ground NaNO2 (1.95 g,
0.028 mol) was slowly added with stirring to sulfuric acid
(3.5 mL). Then a solution of 2,4,6ꢀtriiodoaniline (1) (2.90 g,
6.16 mmol) in glacial AcOH (130 mL) was added dropwise with
stirring and cooling at such a rate that the temperature of the
reaction mixture was kept below 20 °C. Following addition of
the amine, the reaction mixture was stirred at ≈20 °C for about
30 min. The resulting solution of the diazonium salt was added
dropwise to a suspension of copper(I) oxide (2.52 g) in dry ethaꢀ
nol (70 mL) with vigorous stirring over 15 min. The reaction
mixture was brought to boiling and stirred for 30 min until
elimination of nitrogen ceased. Then the mixture was cooled,
kept for one day, poured into ice water (300 mL), and extracted
with benzene (3×50 mL). The benzene extracts were dried with
anhydrous Na2SO4 and the solvent was distilled off in vacuo.
The residue was repeatedly recrystallized from benzene. The
yield was 2.01 g (84%), m.p. 182 °C (cf. lit. data11: m.p. 183 °C).
1H NMR (CDCl3), δ: 8.02 (s, 3 H, CH). 13C NMR (CDCl3),
δ: 79; 128.
2,6ꢀdiiodoꢀ4ꢀnitroaniline,11 or by the reaction of the
Grignard reagent from 1,3,5ꢀtribromobenzene with
1,2ꢀdiiodoethane.12 All the aboveꢀmentioned procedures
afford the desired products in yields of no higher than
75% and require the synthesis of commercially unavailꢀ
able starting reagents and/or drastic reaction conditions.
Reductive deamination of triiodoaniline 1 according
to a standard procedure13 gives rise to triiodobenzene 3 in
84% yield (Scheme 2).
Scheme 2
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 03ꢀ03ꢀ
32401a).
1,3,5ꢀTriiodobenzene is used in the cascade
Heck—Diels—Alder reaction for the synthesis of various
spiro compounds,14 for the preparation of trigonal and
tetragonal connectors in the construction of supramoꢀ
lecular systems,15 in the synthesis of organometallic comꢀ
pounds,16 for the preparation of porphyrin derivatives,17
and in the Stille reaction with organotin compounds.18
References
1. K. Sonogashira, Y. Tohda, and N. Hagihara, Tetrahedron
Lett., 1975, 50, 4467; S. Takanashi, Y. Kuroyama,
K. Sonogashira, and N. Nagihara, Synthesis, 1980, 8, 627;
T. Sakamoto, M. Shiraiwa, Y. Kondo, and H. Yamanaka,
Synthesis, 1983, 4, 312; T. Jeffery, Tetrahedron, 1996,
52, 10113; A. A. Moroz, M. S. Shvartsberg, and I. L.
Kotlyarevskii, Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 4,
851 [Bull. Acad. Sci. USSR, Div. Chem. Sci., 1979, 28 (Engl.
Transl.)]; A. A. Moroz, M. S. Shvartsberg, and I. L.
Kotlyarevskii, Izv. Akad. Nauk SSSR, Ser. Khim., 1979, 1661
[Bull. Acad. Sci. USSR, Div. Chem. Sci., 1979, 28 (Engl.
Transl.)]; W. Tao, S. Nesbitt, and R. F. Heck, J. Org. Chem.,
1990, 55, 63; M. Erdelyi and A. Gogoll, J. Org. Chem., 2001,
66, 4165.
Experimental
The starting reagents were purified according to standard
procedures.19 Potassium dichloroiodate was synthesized accordꢀ
ing to a known procedure.20
The 1H and 13C NMR spectra were recorded on a
VarianꢀXRꢀ400 instrument operating at 400 and 100 MHz, reꢀ

Diꢀ and triiodoanilines
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 2, February, 2004
473
2. H. Dorn, Chem. Ber., 1957, 90, 455.
11. C. Wilgerodt and E. Arnold, Ber., 1901, 34, 3343; M. Hirota
and K. Kitajima, Bull. Chem. Soc. Jpn., 1967, 40, 2197.
12. N. Rot and F. Bickelhaupt, Organometallics, 1997, 16, 5027.
13. H. H. Hodgson and H. S. Turner, J. Chem. Soc., 1942, 748.
14. H. Nüske, S. Bräse, S. Kozhushkov, M. Noltemeyer,
M. EsꢀSayed, and A. de Meijere, Chem. Eur. J., 2002, 8, 2350.
15. P. F. H. Schwab, B. C. Noll, and J. Michl, J. Org. Chem.,
2002, 67, 5476.
3. A. Hautzsch, Ber., 1903, 36, 2070; T. Michael and S. Norton,
Ber., 1878, 11, 111; S. Jackson and H. Whitmore, J. Am.
Chem. Soc, 1915, 37, 1522; F. Bradfield, A. Orton, and
S. Roberts, J. Chem. Soc., 1928, 783.
4. W. Wheeler and P. Liddle, J. Am. Chem. Soc., 1920, 42, 457;
K. Borsche, T. Weussmann, and F. Fritzsche, Ber., 1924,
57, 1774.
5. V. K. Chaikovskii, V. D. Filimonov, and V. I. Skorokhodov,
Izv. Akad. Nauk, Ser. Khim., 2001, 2302 [Russ. Chem. Bull.,
Int. Ed., 2002, 50, 2411].
16. H. Yao, M. Sabat, and R. N. Grimes, Organometallics, 2002,
21, 2833; S. K. Hurst, M. P. Cifuentes, and M. G.
Humphrey, Organometallics, 2002, 21, 2353.
6. H. A. Muathen, J. Chem. Res., Synopsis, 1994, 11, 405.
7. X. Ding, G. Liu, J. Xu, and G. Xu, Pharmaceutical Industry,
1988, 19, 439 (in Chinese); Chem. Abstrs., 1989, 111, 438939.
8. S. Kajigaeshi, T. Kakinami, H. Yamasaki, S. Fujisaki, and
T. Okamoto, Bull. Chem. Soc. Jpn., 1988, 61, 600.
9. U. Schoeberl, T. F. Magnera, R. M. Harrison, F. Fleischer,
J. L. Pflug, P. F. H. Schwab, X. Meng, D. Lipiak, B. C.
Noll, V. S. Allured, T. Rudalevige, S. Lee, and J. Michl,
J. Am. Chem. Soc., 1997, 119, 3907; A. Godt, C. Franzen,
S. Veit, V. Enkelmann, M. Pannier, and G. Jeschke, J. Org.
Chem., 2000, 65, 7575; H. Suzuki, A. Kondo, and T. Ogawa,
Chem. Lett., 1985, 3, 411.
17. S. Rucareanu, O. Mongin, A. Schuwey, N. Hoyler,
A. Gossauer, W. Amrein, and H.ꢀU. Hediger, J. Org. Chem.,
2001, 66, 4973.
18. Y.ꢀH. Fan and J. Haseltine, J. Heterocycl. Chem., 1999,
36, 869.
19. L. F. Tietze and T. Eicher, Reactionen und Synthesen im
organisch chemischen Praktikum und Forschungslaboratorium,
Georg Thieme Verlag, Stuttgart—New York, 199.
20. H. W. Cremer and D. R. Duncan, J. Chem. Soc., 1931, 1863;
F. Ephraim, Ber., 1917, 50, 1086.
Received September 19, 2003;
10. US Pat. 4012454; Chem. Abstrs., 1977, 87, 534442.
in revised form December 17, 2003