A solvent-free synthesis of (dichloroiodo)arenes from iodoarenes

Article abstract of DOI:10.1016/j.tetlet.2003.11.071

An efficient solid-state oxidation of iodoarenes, ArI, is described using the urea-hydrogen peroxide adduct (UHP), a stable, inexpensive, and easily handled oxidant. The reactions were complete in 15min at 85°C. The melts thus obtained were reacted with e

Full text of DOI:10.1016/j.tetlet.2003.11.071

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1087–1089
A solvent-free synthesis of (dichloroiodo)arenes from iodoarenes
Agnieszka Zielinska and Lech Skulski*
Chair and Laboratory of Organic Chemistry, Faculty of Pharmacy, Medical University, 1 Banacha Street, PL 02-097 Warsaw, Poland
Received 26 August 2003; revised 5 November 2003; accepted 14 November 2003
Abstract—An efficient solid-state oxidation of iodoarenes, ArI, is described using the urea–hydrogen peroxide adduct (UHP), a
stable, inexpensive, and easily handled oxidant. The reactions were complete in 15 min at 85 ꢀC. The melts thus obtained were
reacted with excess hydrochloric acid to afford crude (dichloroiodo)arenes, ArICl2, in 64–98% yields.
ꢁ 2003 Elsevier Ltd. All rights reserved.
1. Introduction
preparations of PhICl2 (in 94% crude yield) on a 20 kg
scale have been conducted by the direct chlorination of
PhI (dissolved in CH2Cl2), at )3 to +4 ꢀC. Furthermore
it was possible to selectively monochlorinate 4-amino-
acetophenone with crude PhICl2 on a 25 kg scale, in 87%
yield.3
(Dichloroiodo)arenes, ArICl2, have found growing
importance in modern organic synthesis.1 More stable,
solid (dichloroiodo)arenes, for example, (dichloro-
iodo)benzene PhICl2, are used as potent and fairly
selective chlorinating and/or oxidizing agents. They have
a practical advantage over elemental chlorine (dichlo-
rine), due to their easy and safe handling. Moreover,
they can be readily converted to other important organic
hypervalent iodine reagents, which also play an impor-
tant role in organic synthesis, viz. iodosylarenes,
iodylarenes, (diacyloxyiodo)arenes, (difluoroiodo)-
arenes, or diaryliodonium salts, etc.1
The inconvenient use of hazardous gaseous Cl2 to afford
ArICl2 from ArI can be avoided using a number of
biphasic or monophasic procedures. They are related
and discussed in our two latest reviews,4;5 which cover in
particular the novel methods devised in our laboratory;
see Ref. 4, pp 1346–1352. Most of the reported methods
demand the use of iodoarenes, ArI, as the starting
substrates, which are oxidatively chlorinated at their
iodine atoms. In 2001, we published two papers, where
we reported relatively simple, two- or three-stage pro-
cedures for the one-pot conversions of various arenes,
ArH, to the corresponding (dichloroiodo)arenes, which
were obtained in high crude yields.6;7
(Dichloroiodo)arenes are yellow crystalline compounds,
are light and heat sensitive and often unstable on
storing. They do not usually give satisfactory micro-
analyses and due to their thermal liability, their melting
points are rather uncertain, depending upon the purity
of the crude products prepared, the time elapsed since
their preparation, and the rate of heating during deter-
minations of their melting/decomposition points.
In 1999, Varma and Naicker8 reported an efficient solid-
state oxidation of hydroxylated aldehydes and ketones
(to hydroxylated phenols), sulfides (to sulfoxides or
sulfones), nitriles (to amides), and nitrogen heterocycles
(to N-oxides). The starting materials were added to the
finely powdered urea–hydrogen peroxide adduct (UHP)
in glass test tubes, and the reaction mixtures were placed
in an oil bath at 85 ꢀC for 7–180 min. The resulting
reaction mixtures were extracted and typically further
worked up to afford the crude products, which were
purified by chromatography. The authors8 emphasized
that this solvent-free oxidative protocol using an inex-
pensive (commercially available), safe, and easily han-
dled reagent, viz. UHP, was a simple and efficient
In 1886, Willgerodt developed the most common
method up to now for preparing ArICl2, by passing a
stream of Cl2 through solutions of ArI dissolved in
CHCl3, at 0 ꢀC; the yields are generally excellent when
this method is applicable.2 Quite recently, the repeated
Keywords: Solid-state oxidation; Urea–hydrogen peroxide adduct as
oxidant; Iodoarenes; (Dichloroiodo)arenes.
* Corresponding author. Fax: +48-22-5720643; e-mail: lskulski@
farm.amwaw.edu.pl
0040-4039/$ - see front matter ꢁ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.11.071

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A. Zielinska, L. Skulski / Tetrahedron Letters 45 (2004) 1087–1089
protocol, applicable to a variety of organic molecules.
The operational simplicity, rapid reaction rates, and
formation of pure products in high yields at a moderate
temperature make their method superior to many
existing protocols. Hence, we have decided to apply this
method to oxidize ArI with solid UHP (used in 100%
excess; larger excesses did not increase the yields), at
85 ꢀC for 15 min, to obtain composite mixtures of urea
with iodosylarenes, ArIO, probably also admixed with
iodylarenes, ArIO2 (which may also be formed therein
by the thermal disproportionation of ArIO: 2ArIO
fi ArIO2+ArI) (Scheme 1).1;2
In our opinion, the novel effective approach, presented
in this paper, for the simple, quick, and safe synthesis of
(dichloroiodo)arenes from iodoarenes is worthy of
mention. Good crude yields (64–98%) and high purities
(96–99%, by iodometry9) of the (dichloroiodo)arenes
thus obtained (Table 1) support our opinion.
2. Experimental
2.1. General
After cooling, the crushed melts thus obtained were
added portionwise to excess concentrated (36%) hydro-
chloric acid, which resulted in effective formation of the
desired (dichloroiodo)arenes (Scheme 2).
All the reagents were purchased from Aldrich and were
used without further purification. The melting/decom-
position points of the freshly prepared (di-
chloroiodo)arenes (Table 1) are uncorrected and were
measured as follows: after an approximate mp had been
taken in an open capillary tube, a new sample was
introduced about 10 ꢀC below this point, and the tem-
perature was raised at a rate of 10 ꢀC minÀ1, until con-
sistent results were obtained.
After 1 h, the yellow precipitates were isolated by fil-
tration, then washed on the filter with water and
petroleum ether (toxic chlorinated solvents, mostly used
in the past, are less effective). After air drying in the
dark, their melting/decomposition points were in good
agreement with those reported in the literature
(Table 1).
2.2. Typical procedure
Iodoarene (4 mmol) was added to finely powdered UHP,
98% (768 mg, 8.0 mmol; 100% excess) in a glass test tube,
and the uniformly dispersed (by shaking) reaction mix-
ture was placed in an oil bath at 85 ꢀC for 15 min. After
cooling, the crushed melt was added portionwise, with
stirring, to excess concd (36%) hydrochloric acid (75 mL,
85 ºC
ArIO + [UREA] + H2O
Ar-I + [UREA]···H2O
Ar-I + 2[UREA]···H2O
85 ºC
ArIO2 + 2[UREA] + 2H2O
Scheme 1.
ArIO + conc. aq. HCl (in excess)
ArIO2 + conc. aq. HCl (in excess)
↓ArICl2 + H2O
(see Refs. 1, 2
)
↓ArICl2 + 2H2O + Cl2 (see Ref.
2, p 36)
Scheme 2.
Table 1. Crude yields and melting points (with decomposition) of the (dichloroiodo)arenes prepared
Substrate
Product
Yield (%)
Mp (ꢀC)
Literature mp (ꢀC)
C6H5I
C6H5ICl2
87a
91
88
96
73
82
74
88
78
90
78
69
84
64
91
67
98
92
96
111–112
89–90
97–98
93–95
89–91
68
112–1137
8812
2-MeC6H4I
3-MeC6H4I
4-MeC6H4I
2,4-Me2C6H3I
2-MeOC6H4I
3-MeOC6H4I
4-MeOC6H4I
2-FC6H4I
2-MeC6H4ICl2
3-MeC6H4ICl2
4-MeC6H4ICl2
2,4-Me2C6H3ICl2
97–9811
97–986
9010
6310
b
2-MeOC6H4ICl2
3-MeOC6H4ICl2
b
70–71
72
7410
75–767
b
4-MeOC6H4ICl2
2-FC6H4ICl2
79–80
104–105
98–100
98
Not reported
104.5–10511
92.5–9511
96–9711
110–1127
93–957
126–129, 136–1387
17210
100–11413
183–1857
26714
4-FC6H4I
2-ClC6H4I
4-FC6H4ICl2
2-ClC6H4ICl2
3-ClC6H4I
4-ClC6H4I
3-ClC6H4ICl2
4-ClC6H4ICl2
113–115
95–97
133–135
173–175
100–102
184–186
267–269
2,4-Cl2C6H3I
4-IC6H4I
2,4-Cl2C6H3ICl2
4-IC6H4ICl2
4-O2NC6H4I
2-HOOCC6H4I
3-HOOCC6H4I
4-HOOCC6H4I
4-O2NC6H4ICl2
2-HOOCC6H4ICl2
3-HOOCC6H4ICl2
4-HOOCC6H4ICl2
b
a When we increased the preparative scale 10-fold, the crude yield was the same; mp 111–112 ꢀC (dec), purity 98%.
b The compounds were unstable, and quickly decomposed on standing, even in a freezer; cf. Ref. 12.

A. Zielinska, L. Skulski / Tetrahedron Letters 45 (2004) 1087–1089
1089
2. Willgerodt, C. Die organischen Verbindungen mit mehrver-
tigem Jod; Enke: Stuttgart, 1914.
3. Zanka, A.; Takeuchi, H.; Kubota, A. Org. Process Res.
Dev. 1998, 2, 270–273.
4. Skulski, L. Molecules 2000, 5, 1331–1371.
5. Skulski, L. Molecules 2003, 8, 45–52.
6. Obeid, N.; Skulski, L. Molecules 2001, 6, 869–874.
7. Lulinski, P.; Obeid, N.; Skulski, L. Bull. Chem. Soc. Jpn.
2001, 74, 2433–2434.
ca. 850 mmol) in a fume hood. After 1 h, the yellow
precipitate was collected by filtration, washed well with
water (to remove HCl and urea) and petroleum ether
(2 · 10 mL, to remove any unreacted ArI), and air dried
in the dark. Iodometric titrations9 indicated that the
freshly prepared crude ArICl2 had a 96–99% purity.
8. Varma, R. S.; Naicker, K. P. Org. Lett. 1999, 1, 189–191.
9. Lucas, H. J.; Kennedy, E. R.; Formo, M. W. Org. Synth.
1942, 22, 70.
References and notes
10. Beringer, F. M.; Gindler, E. M. Iodine Abstr. Rev. 1956, 3,
1–70.
11. Obeid, N.; Skulski, L. Pol. J. Chem. 2000, 74, 1609–1615.
12. Koyuncu, D.; McKillop, A.; McLaren, L. J. Chem. Res.
(S) 1990, 21.
13. Karele, B. Ya.; Neiland, O. Ya. Latv. PSR Zinat. Akad.
Vestis, Kim. Ser. 1970, 587–590; Chem. Abstr. 1971, 74,
42033.
14. Keefer, R. M.; Andrews, L. J. J. Am. Chem. Soc. 1958, 80,
277–281.
1. (a) Varvoglis, A. The Organic Chemistry of Polycoordi-
nated Iodine; VCH: Weinheim, 1992; (b) Stang, P. J.;
Zhdankin, V. V. Chem. Rev. 1996, 96, 1123–1178; (c)
Varvoglis, A. Hypervalent Iodine in Organic Synthesis;
Academic: San Diego, 1997; (d) Zhdankin, V. V.; Stang, P.
J. Chem. Rev. 2002, 102, 2523–2584; (e) Hypervalent Iodine
Chemistry; Wirth, T., Ed.; Springer: Ijmuiden, Nether-
land, 2003; Vol. 224; (f) Stang, P. J. J. Org. Chem. 2003,
68, 2997–3008.