Synthesis and reactivity of fluorous and nonfluorous aryl and alkyl iodine(III) dichlorides: New chlorinating reagents that are easily recycled using biphasic protocols

Article abstract of DOI:10.1021/jo900233h

Fluorous aryl and alkyl iodine(III) dichlorides of the formulas (R _fn(CH₂)₃)₂C₆H ₃ICl₂ (R_fn ) CF₃(CF ₂)_n-1; n ) 8 for 3,5-disubstituted and n ) 6, 8, 10 for 2,4-disubstituted) and R_fnCH₂ICl₂ (n ) 8, 10) are prepared in 71-98% yields by reactions of Cl₂ and the corresponding fluorous iodides. These are effective reagents for the conversions of cyclooctene to trans-1,2-dichlorocyclooctene, anisole to 4-chloro- and 2-chloroanisole, 4-tert-butylphenol to 2-chloro-4-tert-butylphenol, PhCOCH ₂COPh to PhCOCHClCOPh, and PhCOCH₃ to PhCOCH₂Cl and PhCOCHCl₂ (CH₃CN, rt to 40°C, 100-64% conversions). The chlorinated products and fluorous iodide coproducts are easily separated by organic/fluorous liquid/liquid biphase workups. The latter are obtained in 97-90% yields and reoxidized with Cl₂. Analogous chlorinations are conducted with 3-Cl₂IC₆H₄COOH (16) and 4,4'-Cl₂IC₆H₄C₆H ₄ICl₂. With the former, the products and coproduct 3-IC₆H₄COOH (91-85% recoveries) are easily separated by organic/aqueous NaHCO₃ liquid/ liquid biphase workups. The coproduct from the latter, 4,4'-IC₆H₄C₆H₄I, is insoluble in common organic solvents, allowing separation by liquid/solid phase workups (91-89% recoveries). The effect of the structure of the iodine(III) dichloride upon reactivity is analyzed in detail. The fluorous systems with R_f8 substituents are generally superior, but 16 is more reactive and gives higher selectivities.

Full text of DOI:10.1021/jo900233h

Synthesis and Reactivity of Fluorous and Nonfluorous Aryl and
Alkyl Iodine(III) Dichlorides: New Chlorinating Reagents that are
Easily Recycled using Biphasic Protocols
Ajda Podgorsˇek,† Markus Jurisch,‡ Stojan Stavber,† Marko Zupan,§ Jernej Iskra,*,† and
John A. Gladysz*,‡,|
Department of Physical and Organic Chemistry, “Jozˇef Stefan” Institute, JamoVa 39, 1000 Ljubljana,
SloVenia, Institut fu¨r Organische Chemie and Interdisciplinary Center for Molecular Materials,
Friedrich-Alexander-UniVersita¨t Erlangen-Nu¨rnberg, Henkestrasse 42, D-91054 Erlangen, Germany,
Faculty of Chemistry and Chemical Technology, UniVersity of Ljubljana, AsˇkercˇeVa 5, 1000 Ljubljana,
SloVenia, and Department of Chemistry, Texas A&M UniVersity, P.O. Box 30012, College Station,
Texas 77842-3012
jernej.iskra@ijs.si; gladysz@mail.chem.tamu.edu
ReceiVed February 3, 2009
Fluorous aryl and alkyl iodine(III) dichlorides of the formulas (Rfn(CH2)3)2C6H3ICl2 (Rfn ) CF3(CF2)n-1;
n ) 8 for 3,5-disubstituted and n ) 6, 8, 10 for 2,4-disubstituted) and RfnCH2ICl2 (n ) 8, 10) are prepared
in 71-98% yields by reactions of Cl2 and the corresponding fluorous iodides. These are effective reagents
for the conversions of cyclooctene to trans-1,2-dichlorocyclooctene, anisole to 4-chloro- and 2-chloro-
anisole, 4-tert-butylphenol to 2-chloro-4-tert-butylphenol, PhCOCH2COPh to PhCOCHClCOPh, and
PhCOCH3 to PhCOCH2Cl and PhCOCHCl2 (CH3CN, rt to 40 °C, 100-64% conversions). The chlorinated
products and fluorous iodide coproducts are easily separated by organic/fluorous liquid/liquid biphase
workups. The latter are obtained in 97-90% yields and reoxidized with Cl2. Analogous chlorinations are
conducted with 3-Cl2IC6H4COOH (16) and 4,4′-Cl2IC6H4C6H4ICl2. With the former, the products and
coproduct 3-IC6H4COOH (91-85% recoveries) are easily separated by organic/aqueous NaHCO3 liquid/
liquid biphase workups. The coproduct from the latter, 4,4′-IC6H4C6H4I, is insoluble in common organic
solvents, allowing separation by liquid/solid phase workups (91-89% recoveries). The effect of the
structure of the iodine(III) dichloride upon reactivity is analyzed in detail. The fluorous systems with Rf8
substituents are generally superior, but 16 is more reactive and gives higher selectivities.
1. Introduction
easy handling, high efficiency, and mild reaction conditions.1
They constitute safe alternatives to heavy metal reagents for a
wide range of transformations, especially oxidations.2 Despite
their increasingly wide application, their low atom economy
Hypervalent iodine reagents have been recognized as exceed-
ingly useful tools in synthesis and promising candidates for
environmentally benign processes. In the latter context, they
have received growing interest due to their useful oxidizing
properties, combined with their low toxicity, ready availability,
(1) (a) Zhdankin, V. V.; Stang, P. J. Chem. ReV. 2002, 102, 2523–2584;
Chem. ReV. 2008, 108, 5299-5358. (b) Ladziata, U.; Zhdankin, V. V. ArkiVoc
2006, 26–58. (c) Varvoglis, A. The Organic Chemistry of Polycoordinated Iodine;
VCH Publishers, Inc.: New York, 1992.
(2) (a) Moriarty, R. M. J. Org. Chem. 2005, 70, 2893–2903. (b) Richardson,
R. D.; Wirth, T. Angew. Chem., Int. Ed. 2006, 45, 4402–4404; Angew. Chem.
2006, 118, 4510-4512. (c) Wirth, T. Angew. Chem., Int. Ed. 2005, 44, 3656–
3665; Angew. Chem. 2005, 117, 3722-3731.
† “Jozˇef Stefan” Institute.
‡ Friedrich-Alexander-Universita¨t Erlangen-Nu¨rnberg.
§ University of Ljubljana.
| Texas A&M University.
10.1021/jo900233h CCC: $40.75
Published on Web 03/25/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 3133–3140 3133

Podgorsˇek et al.
remains a major drawback, as stoichiometric amounts of aryl
iodides or similar waste products are produced.3 This represents
a distinct debit from a “green” chemistry viewpoint. A possible
solution would be the recycling and reuse of reaction coproducts,
which reduces Sheldon’s environmental factor E.4 Accordingly,
a number of approaches to recyclable hypervalent iodine
reagents have been reported involving both polymeric5-10
(polystyrene or silica supports) and molecular species,11-13
among which iodine(III) bis(acetates) and bis(trifluoroacetates)
dominate.
Recently, several recyclable hypervalent iodine reagents based
on fluorous chemistry principles have been developed.11 Fluo-
rous chemistry, an important part of “green” chemistry,14
exploits the combined lipophobicity and hydrophobicity of
fluorous molecules to effect cleaner reactions and separation
processes. Liquid/liquid or liquid/solid biphasic conditions are
commonly employed to remove “phase tagged” or “ponytailed”
coproducts or catalysts from the product.15 As a case in point,
fluorous aryl iodine(III) bis(acetates) have been shown to be
excellent reagents for oxidations of hydroquinones to quinones
under homogeneous conditions. The resulting fluorous aryl
iodides can be recovered by simple fluorous/organic liquid/liquid
phase separations and reoxidized to the iodine(III)
bis(acetates).11a Many fluorous alkyl iodides RfnI (Rfn
)
CF3(CF2)n-1) are commercially available and can similarly be
converted to fluorous alkyl iodine(III) bis(trifluoroacetates).
These reagents also efficiently oxidize hydroquinones to quino-
nes, as well as secondary aliphatic and benzylic alcohols to
ketones, and the RfnI coproducts are easily recovered and
reoxidized (for less volatile species with n > 8).11b,c
Chlorination constitutes one of the most important transfor-
mations in organic synthesis.16 Molecular chlorine, the most
commonly used chlorinating agent, is a hazardous, toxic, and
corrosive chemical whose high reactivity and highly exothermic
reactions cause difficulties in effecting selective conversions.
Consequently, alternative chlorination reagents (e.g., NCS) and
reaction systems have been developed with increased ease of
handling and selectivity.17 However, drawbacks such as low
atom economy and the need to remove spent reagent remain.
As the chemistry of hypervalent iodine(III) dihalides has
expanded, they have received increasing attention as halogenat-
ing and oxidizing agents, as well as building blocks for other
hypervalent iodine compounds.1 The most frequently encoun-
tered representative is (dichloroiodo)benzene, a molecule that
was first prepared in 1886 by Willgerodt by passing chlorine
through a solution of iodobenzene in an organic solvent.18 This
is still the most general method for preparing (dichloroiodo)are-
nes.
Despite the synthetic importance of (dichloroiodo)benzene,
its broader application as a reagent has been restricted due to
the often tedious separation of the coproduct iodobenzene from
the desired products. To circumvent this problem, a polymer-
supported version has been developed.9a Furthermore, a recent
report described the use of 4,4′-bis(dichloroiodo)biphenyl and
3-(dichloroiodo)benzoic acid for iodochlorinations and io-
doalkoxylations of unsaturated compounds.13d The former gives
a coproduct that is insoluble in most organic solvents, 4,4′-
bis(iodo)biphenyl. The latter gives a coproduct that can be
extracted with aqueous base, 3-iodobenzoic acid. Accordingly,
these have been efficiently recovered by solid/liquid and organic/
aqueous NaHCO3 liquid/liquid biphase protocols, respectively,
and reoxidized to the dichlorides and reused.
(3) (a) Lenoir, D. Angew. Chem., Int. Ed. 2006, 45, 3206–3210; Angew. Chem.
2006, 118, 3280-3284. (b) Constable, D. J. C.; Curzons, A. D.; Cunningham,
V. L. Green Chem. 2002, 4, 521–527.
(4) Anastas, P. T.; Warner; J. C. Green Chemistry: Theory and Practice;
Oxford University Press, Inc.: New York, 1998.
(5) Togo, H.; Sakuratani, K. Synlett 2002, 1966–1975.
(6) (a) Chen, F.-E.; Xie, B.; Zhang, P.; Zhao, J.-F.; Wang, H.; Zhao, L. Synlett
2007, 619–622. (b) Shang, Y.; But, T. Y. S.; Togo, H.; Toy, P. H. Synlett 2007,
67–70. (c) Herrer´ıas, C. I.; Zhang, T. Y.; Li, C. J. Tetrahedron Lett. 2006, 47,
13–17. (d) Teduka, T.; Togo, H. Synlett 2005, 923–926. (e) Qian, W.; Jin, E.;
Bao, W.; Zhang, Y. M. Angew. Chem., Int. Ed. 2005, 44, 952–955; Angew.
Chem. 2005, 117, 974-977. (f) Tashino, Y.; Togo, H. Synlett 2004, 2010–2012.
(g) Ficht, S.; Mu¨lbaier, M.; Giannis, A. Tetrahedron 2001, 57, 4863–4866. (h)
Ley, S. V.; Thomas, A. W.; Finch, H. J. Chem. Soc., Perkin Trans. 1 1999,
669–671. (i) Hossain, M. D.; Kitamura, T. Synthesis 2006, 1253–1256.
(7) (a) Lei, Z.; Denecker, C.; Jegasothy, S.; Sherrington, D. C.; Slater,
N. K. H.; Sutherland, A. J. Tetrahedron Lett. 2003, 44, 1635–1637. (b) More,
J. D.; Finney, N. S. Org. Lett. 2002, 4, 3001–3003. (c) Mu¨lbaier, M.; Giannis,
A. Angew. Chem., Int. Ed 2001, 40, 4393–4394; Angew. Chem. 2001, 113, 4530-
4532. (d) Chung, W.-J.; Kim, D.-K.; Lee, Y.-S. Synlett 2005, 2175–2178.
(8) (a) Tohma, H.; Takizawa, S.; Maegawa, T.; Kita, Y. Angew. Chem., Int.
Ed. 2000, 39, 1306–1308; Angew. Chem. 2000, 112, 1362-1364. (b) Tohma,
H.; Maegawa, T.; Kita, Y. Synlett 2003, 723–725.
ˇ
Surprisingly, there have not been any reports of fluorous
(dichloroiodo)arenes. However, a few fluorous aliphatic
iodine(III) chlorides of the formulas RfnCH2ICl2 (n ) 1-3)
have been synthesized, as well as the related species
H(CF2)6CH2ICl2.19 Importantly, these feature a methylene
“spacer” between the iodine and the highly electron-withdrawing
Rfn moiety. The apparent absence of the spacerless analogues
RfnICl2 in the literature may reflect unfavorable thermodynamics
for the chlorination, or a kinetic barrier. These iodine(III)
compounds have been shown to efficiently dichlorinate alkenes
and monochlorinate 1,3-diketones. However, the RfnCH2I (n )
1-3) coproducts are too volatile for easy recycling.
(9) (a) Sket, B.; Zupan, M.; Zupet, P. Tetrahedron 1984, 40, 1603–1606.
(b) Zupan, M.; Pollak, A. J. Chem. Soc., Chem. Commun. 1975, 715–716. (c)
Kalberer, E. W.; Whitfield, S. R.; Sanford, M. S. J. Mol. Catal. A: Chem. 2006,
251, 108–113.
(10) (a) Karimov, R. R.; Kazhkenov, Z. G. M.; Modjewski, M. J.; Peterson,
E. M.; Zhdankin, V. V. J. Org. Chem. 2007, 72, 8149–8151. (b) Huang, X.;
Zhu, Q. Tetrahedron Lett. 2001, 42, 6373–6375. (c) Abe, S.; Sakuratani, K.;
Togo, H. J. Org. Chem. 2001, 66, 6174–6177.
(11) (a) Rocaboy, C.; Gladysz, J. A. Chem.sEur. J. 2003, 9, 88–95. (b)
Tesevic, V.; Gladysz, J. A. Green Chem. 2005, 7, 833–836. (c) Tesevic, V.;
Gladysz, J. A. J. Org. Chem. 2006, 71, 7433–7440. See also: (d) Lion, C. J.;
Vasselin, D. A.; Schwalbe, C. H.; Matthews, C. S.; Stevens, M. F. G.; Westwell,
A. D. Org. Biomol. Chem. 2005, 3, 3996–4001.
(12) (a) Moroda, A.; Togo, H. Tetrahedron 2006, 62, 12408–12414. (b) Dohi,
T.; Maruyama, A.; Yoshimura, M.; Morimoto, K.; Tohma, H.; Shiro, M.; Kita,
Y. Chem. Commun. 2005, 2205–2207. (c) Tohma, H.; Maruyama, A.; Maeda,
A.; Maegawa, T.; Dohi, T.; Shiro, M.; Morita, T.; Kita, Y. Angew. Chem., Int.
Ed. 2004, 43, 3595–3598; Angew. Chem. 2004, 116, 3679-3682. (d) Stang,
P. J.; Zhdankin, V. V. J. Am. Chem. Soc. 1993, 115, 9808–9809.
(13) (a) Yusubov, M. S.; Funk, T. V.; Chi, K.-W.; Cha, E.-H.; Kim, G. H.;
Kirshning, A.; Zhdankin, V. V. J. Org. Chem. 2008, 73, 295–297. (b) Yusubov,
M. S.; Yusubova, R. Y.; Kirschning, A.; Park, J. Y.; Chi, K.-W. Tetrahedron
Lett. 2008, 49, 1506–1509. (c) Yusubov, M. S.; Gilmkhanova, M. P.; Zhdankin,
V. V.; Kirschning, A. Synlett 2007, 563–566. (d) Yusubov, M. S.; Drygunova,
L. A.; Zhdankin, V. V. Synthesis 2004, 2289–2292.
In this paper, we present the synthesis and characterization
of several fluorous aryl and alkyl iodine(III) dichlorides and
detail their use as recyclable chlorinating reagents for alkenes,
(16) (a) Ullmann’s Encyclopedia of Industrial Chemistry; 6th ed.; Wiley-
VCH: Weinheim, 2002. (b) Fauvarque, J. Pure Appl. Chem. 1996, 68, 1713–
1720.
(14) Gladysz, J. A. Catalysis Involving Fluorous Phases: Fundamentals and
Directions for Greener Methodologies. In Handbook of Green Chemistry; Anastas,
P., Ed.; Crabtree, R. H., Vol. Ed; Wiley/VCH, Weinheim, 2009; Vol. 1:
Homogeneous Catalysis; 17-38.
(15) Handbook of Fluorous Chemistry; Gladysz, J. A., Curran, D. P., Horva´th,
I. T., Eds.; Wiley/VCH: Weinheim, 2004.
(17) (a) Golebiewski, W. M.; Gucma, M. Synthesis 2007, 3599–3619. (b)
Iskra, J.; Stavber, S.; Zupan, M. Chem. Commun. 2003, 2496–2497.
(18) Willgerodt, C. J. Prakt. Chem. 1886, 33, 154–160.
(19) (a) Bravo, P.; Montanari, V.; Resnati, G.; DesMarteau, D. D. J. Org.
Chem. 1994, 59, 6093–6094. (b) Montanari, V.; DesMarteau, D. D.; Pennington,
W. T. J. Mol. Struct. 2000, 550-551, 337–348.
3134 J. Org. Chem. Vol. 74, No. 8, 2009

Fluorous and Nonfluorous Aryl and Alkyl Iodine(III) Dichlorides
SCHEME 1a
SCHEME 2a
a Key: (a) (CF3SO2)2O, pyridine/PhCF3, 0 °C to rt, 12 h; (b) KI,
HOCH2CH2OH, reflux, 12 h.
TABLE 1. Synthesis of Various Iodine(III) Dichloride Reagents
Using Molecular Chlorinea
a Key: (a) (RfnCH2CH2)Ph3P+ I-, K2CO3, p-dioxane/H2O, 95 °C; (b) 10%
Pd/C, 1 atm H2, ethanol/CF3C6H5; (c) I2/H5IO6, AcOH/H2SO4/H2O/reflux
or I2, PhI(OAc)2, AcOEt/reflux.
arenes, and ketones. The effect of the structures of the aryl and
alkyl iodine(III) dichlorides upon their stabilities and reactivities
are carefully defined. Complementary experiments are conducted
with the nonfluorous iodine(III) dichlorides derived from 4,4′-
bis(iodo)biphenyl and 3-iodobenzoic acid.13d As noted above,
these iodoarenes can be recovered by solid/liquid and aqueous/
organic liquid/liquid biphase protocols. Thus, this study repre-
sents one of the few in which the effectiveness of several
competing reagent recycling strategies are compared and
contrasted.
2. Results and Discussion
2.1. Syntheses of Fluorous Aryl Iodides 4 and Alkyl
Iodides 7. The fluorous aryl iodides 3,4-(Rf8(CH2)3)2C6H3I (4a),
2,4-(Rf6(CH2)3)2C6H3I (4b), 2,4-(Rf8(CH2)3)2C6H3I (4c), 2,4-
(Rf10(CH2)3)2C6H3I (4d), and 2,4,6-(Rf8(CH2)3)3C6H2I (4e) can
be synthesized in several simple steps from benzene di- or
tricarbaldehydes C6H6-x(CHO)x (1). As summarized in Scheme
1, Wittig reactions with the appropriate fluorous triphenylphos-
phonium salts were followed by side-chain hydrogenations and
then iodinations of the arene cores. The resulting fluorous aryl
iodides feature two or three ponytails, each with three methylene
spacers. The homologous series 4b,c,d contain increasingly long
Rfn segments, which results in progressively lower absolute
solubilities.14
The syntheses of 2a,c,e, 3a,c,e, and 4a,c,e have been reported
previously,11a,20 and data for the new compounds 2b,d, 3b,d,
and 4b,d are summarized in the Experimental Section and
Supporting Information. While 2b, 3b, and 4b were isolated in
analytically pure form in 78%, 97%, and 75% yields, respec-
tively, 2d, 3d, and 4d could only be obtained in crude form.
The solubilities of compounds with multiple Rf10-containing
ponytails can be especially low, complicating both reactions
and workups.
The fluorous alkyl iodides RfnCH2I (7) were prepared in two
simple steps from the commercially available alcohols
RfnCH2OH (5). As shown in Scheme 2, this involved initial
conversion to the corresponding triflates 6 and subsequent
iodination to give 7. The syntheses of 6a and 7a have been
reported previously.21 Details for 6b and 7b, which were isolated
in analytically pure form in 99% and 87% yields, respectively,
are provided in the Experimental Section.
a Hexane solvent unless noted. b 0.3 equiv of CF3SO3H was added.
c Unstable product. d CHCl3 solvent.
2.2. Syntheses and Properties of Aryl and Alkyl
Iodine(III) Dichlorides. The corresponding fluorous aryl io-
dine(III) dichlorides were sought next. Thus, gaseous chlorine
was bubbled through hexane solutions of 4a-e. Workups of
the resulting yellowish precipitates gave the target molecules
8a-d in 98-71% yields as summarized in Table 1. No
conversion was observed in the case of 4e, showing that two
substituents ortho to the iodine atom suppress chlorination under
these conditions. Accordingly, the yields with the substrates with
one ortho (and one para) substituent (denoted Ar2,4-Rfn) were
slightly lower than that without (Ar3,4-Rf8). The dichlorides 8a-c
were isolated in analytically pure form, and 8d was of >98%
purity.
(20) Rocaboy, C.; Rutherford, D.; Bennett, B. L.; Gladysz, J. A. J. Phys.
Org. Chem. 2000, 13, 596–603.
(21) Alvey, L. J.; Rutherford, D.; Juliette, J. J. J.; Gladysz, J. A. J. Org.
Chem. 1998, 63, 6302–6308.
The fluorous aryl iodine(III) dichlorides 8a-d are pale yellow
solids that are stable in a freezer for weeks. They exhibit good
solubilities in CHCl3, decreasing as expected for 8b-d as the
J. Org. Chem. Vol. 74, No. 8, 2009 3135

Podgorsˇek et al.
TABLE 2. Reactions of Aryl and Alkyl Iodine(III) Dichlorides
with Cyclooctene: Conditions Required for Complete Conversiona
SCHEME 3. Trapping of Unstable Rf8CH2CH2ICl2 with
Cyclooctene (22)
reagent
conditions (time, h; T, °C)
8a, Ar3,4-Rf8
8b, Ar2,4-Rf6
8c, Ar2,4-Rf8
8d, Ar2,4-Rf10
9a, Rf8CH2
9b, Rf10CH2
16, Araq
8, rt
8, rt
8, 40
8, 40
3, 40
10, 40
0.5, rt
8, 40
2, rt
18, Arsolid
20, Ar
a
1
Determined by H NMR spectroscopy.
Rfn segment is lengthened. They are slightly soluble in methanol,
CH2Cl2, Et2O, and C6F14.
chlorine,23 it was stored as a solid in the freezer. The parent
compound (dichloroiodo)benzene (20) was also prepared for
reference experiments. This light- and heat-sensitive yellow
crystalline solid can be stored in a freezer for approximately 2
weeks.1c Although all of these reactions are known, the
syntheses are detailed in the Supporting Information and the
yields incorporated into Table 1 to facilitate comparisons with
the fluorous reagents.
Related aliphatic fluorous iodine(III) dichlorides would offer
several potential advantages, such as shorter syntheses and lower
molecular weights. Therefore, the chlorination of fluorous alkyl
iodides with varying Rfn segment and methylene spacer lengths
was investigated. As can be seen from the results in Table 1,
the number of methylene groups has a marked effect upon the
reactivity with chlorine and on the stability of the resulting
iodine(III) dichlorides. In the absence of a methylene spacer
(Rf8I, 10), chlorination did not occur, presumably due to the
electron-withdrawing effect of the perfluoroalkyl chain. Even
the presence of 1 equiv of CF3SO3H as a catalyst did not activate
10 for chlorination. In contrast, and in accord with literature
precedent noted above,19 the single methylene spacer in 7a,b
provided sufficient insulation, enabling chlorination to 9a,b to
proceed in the presence of 0.3 equiv of CF3SO3H. These
compounds were isolated as analytically pure yellow solids that
were stable in a freezer for weeks. However, they had very low
solubilities in common organic solvents. The chlorination of
commercial Rf8CH2CH2I (11), which features two methylene
spacers, was studied next. Chlorine addition occurred in the
absence of any CF3SO3H catalyst, but the presumed product
Rf8CH2CH2ICl2 (12) rapidly decomposed upon attempted isola-
tion, with evolution of gaseous iodine chloride and formation
of the fluorous alkyl chloride Rf8CH2CH2Cl (21)22 (Scheme 3).
A related nonfluorous substrate, octyl iodide (13), behaved
similarly. The formation of 12 was strongly supported by a
trapping reaction with cyclooctene (22) (Scheme 3). When the
chlorination of 11 was performed at 0 °C in hexane, 12
precipitated. An equimolar amount of 22 was then added. The
precipitate vanished and 22 was transformed mainly to trans-
1,2-dichloro-cyclooctane (23; 78%). Some trans-1-chloro-2-
iodocyclooctane (24; 11%) also formed as assayed by 1H NMR
spectroscopy of the crude reaction mixture. When an analogous
experiment was conducted in acetonitrile, which yielded a brown
solution characteristic of ICl, 24 was obtained as the sole
product.
2.3. Aryl and Alkyl Iodine(III) Dichlorides As Recyclable
Chlorinating Reagents. Several representative organic sub-
strates were selected for chlorination studies: cyclooctene (22),
anisole (25), 4-tert-butylphenol (28), 1,3-diphenylpropane-1,3-
dione (30), and acetophenone (32). Reactions with the alkene
22 were screened first. In all experiments, 0.10 mmol of 22
was dissolved in 1.0 mL of acetonitrile, and 0.10 mmol of the
iodine(III) reagent was added. The mixture was then stirred at
room temperature or 40 °C until the reagent was consumed.
The acetonitrile was replaced by a deuterated solvent and the
1
conversion assayed by H NMR. As summarized in Table 2,
all iodine(III) reagents quantitatively transformed 22 into trans-
1,2-dichlorocyclooctane (23). However, the aryl or alkyl sub-
stituent greatly affected reactivity. The resulting aryl and alkyl
iodides were then recovered via various procedures as described
below.
With the fluorous iodine(III) dichlorides 8 and 9, a fluorous/
organic liquid/liquid biphase system was employed for separa-
tion of the product from the spent reagent. In the case of Ar3,4-
Rf8 8a, which is soluble in acetonitrile, the chlorination was
performed at room temperature under homogeneous conditions.
After 8 h, the acetonitrile was replaced by C6F14 and 80-90%
aqueous methanol. The product 23 partitioned into the upper
aqueous methanol phase, whereas the iodine(I) coproduct 4a
partitioned into the lower fluorous phase. In this context, the
perfluoromethylcyclohexane/methanol partition coefficients of
4a,c have been reported as (97.0-98.6):(3.0-1.4).11a After
phase separation, workup (Experimental Section) gave 23 in
95% yield and 4a in 95% yields. The C6F14 was recovered and
reused.
The reagent Ar2,4-Rf6 8b could be employed in exactly the
same way. However, the other fluorous iodine(III) dichlorides
8c,d and 9a,b were not as soluble in acetonitrile at room
temperature. In the case of Ar2,4-Rf8 8c, homogeneous conditions
could be achieved at 40 °C. Although Rf8CH2 9a remained
incompletely soluble at 40 °C, the reaction mixture became
Next, the nonfluorous aryl iodine(III) dichlorides, 3-(dichlor-
oiodo)benzoic acid (16) and 4,4′-bis(dichloroiodo)biphenyl (18),
required for the alternative recycling protocols noted above, were
prepared as described earlier.13d Since the former slowly
equilibrates in acetic acid with 3-iodobenzoic acid (15) and
(22) (a) Consorti, C. S.; Jurisch, M.; Gladysz, J. A. Org. Lett. 2007, 9, 2309–
2312. (b) Mandal, D.; Jurisch, M.; Consorti, C. S.; Gladysz, J. A. Chem. Asian
J. 2008, 3, 1772–1782.
(23) Andrews, L. J.; Keefer, R. M. J. Am. Chem. Soc. 1959, 81, 4218–4223.
3136 J. Org. Chem. Vol. 74, No. 8, 2009

Fluorous and Nonfluorous Aryl and Alkyl Iodine(III) Dichlorides
SCHEME 4. Schematic Representation of Chlorination with
Fluorous Iodine(III) Dichlorides 8 and 9, Illustrated for 9a
SCHEME 6. Schematic Representation of Chlorination with
4,4′-Bis(dichloroiodo)biphenyl (18)
TABLE 3. Reactions of Aryl and Alkyl Iodine(III) Dichlorides
with Anisole (25)
SCHEME 5. Schematic Representation of Chlorination with
3-(Dichloroiodo)benzoic Acid (16)
conditions
(time, h; T, °C)
conva
(%)
ratio
26/27
selectivity
26/27
reagent
8a, Ar3,4-Rf8
8b, Ar2,4-Rf6
8c, Ar2,4-Rf8
8d, Ar2,4-Rf10
9a, Rf8CH2
9b, Rf10CH2
16, Araq
24, rt
8, rt
100
100
92
100
100
100
100
100
95
48:52
57:43
87:13
71:29
86:14
79:21
88:12
82:18
80:20
0.92
1.33
6.69
2.45
6.14
3.76
7.33
4.56
4.00
24, 40
8, 40
8, 40
24, 40
1, rt
18, Arsolid
20, Ar
24, 40
2, rt
a
1
homogeneous as 22 was consumed. In contrast, in chlorinations
involving reagents with longer Rf10 perfluoroalkyl chains, Ar2,4-
Rf10 8d and Rf10CH2 9b, white solids persisted throughout the
reaction, consistent with the low solubilities of the coproducts
4d and 7b. However, all of the fluorous aryl and alkyl iodides
could be recycled exactly as 4a, as illustrated for 7a in Scheme
4. Yields were 97-90%.
Next, the analogous reaction of 3-(dichloroiodo)benzoic acid
(Araq, 16) was investigated. This reagent did not completely
dissolve in acetonitrile at room temperature. Nevertheless, it
gave the fastest chlorination of 22, requiring only 0.5 h. The
acetonitrile was replaced by an aqueous/organic biphase system
consisting of 5% aqueous NaHCO3 and petroleum ether. After
phase separation, workup (Experimental Section) gave 23 in
93% yield and 3-iodobenzoic acid (15) in 91% yield (isolated
by filtration of the acidified aqueous phase). The recycling
procedure is summarized in Scheme 5. With all of the substrates
that follow below, recoveries of 15 were 91-85%.
The reagent 4,4′-bis(dichloroiodo)biphenyl (Arsolid, 18) was
then studied. Chlorinations were conducted at 40 °C due to the
very low solubility of 18 in acetonitrile at room temperature.
However, the reaction mixture remained heterogeneous. Over
the course of 8 h, undissolved pale yellow 18 was replaced by
the white 4,4′-diiodobiphenyl (17) coproduct. The acetonitrile
was then replaced by methanol, in which 17 is poorly soluble.
Simple filtration gave 17 in 91% yield. The product 23 remained
dissolved in the filtrate, which also contained traces of 17. When
hexane was used in place of methanol, recoveries of 17 were
lower. The recycling procedure is summarized in Scheme 6.
With all of the substrates that follow, recoveries of 17 were
91-89%.
Determined by H NMR spectroscopy.
An analogous reaction with (dichloroiodo)benzene 20 pro-
ceeded quite rapidly (2 h) under homogeneous conditions at
room temperature. However, 23 could only be separated from
the coproduct iodobenzene (19) by column chromatography.
In order to gauge the generality of the preceding chlorination
and recovery protocols, organic substrates bearing other func-
tional groups were investigated. The chlorination of anisole (25)
normally gives a mixture of p-chloroanisole (26) and o-
chloroanisole (27). As shown in Table 3, reaction with Ar3,4-
Rf8 8a in acetonitrile required ca. 24 h at room temperature and
afforded a 48:52 26/27 ratio. Conversions were assayed as in
Table 2. With Ar2,4-Rf6 8b, which features a substituent ortho
to the iodine, the selectivity for para chlorination was slightly
higher (57:43). When the lengths of the ponytails were extended
(Ar2,4-Rf8 8c and Ar2,4-Rf10 8d) para selectivities increased
further (87:13 and 71:29), despite the higher reaction temper-
atures (40 °C). Curiously, selectivities with the fluorous alkyl
iodine(III) dichlorides Rf8CH2 9a and Rf10CH2 9b (86:14 and
79:21) were similar. Interestingly, the nonfluorous reagent Araq
16 proved to be the most reactive and selective of all, giving a
complete reaction within 1 h at room temperature and a 88:12
26/27 ratio. Arsolid 18, being very poorly soluble in acetonitrile,
required heating and longer reaction times, while 20 was more
reactive and gave a selectivity similar to that of 18 (80:20 vs
82:18).
The chlorination of another arene, 4-tert-butylphenol (28,
Table 4), was analogously investigated. In all cases, only
2-chloro-4-tert-butylphenol (29) was observed. No dichlorination
J. Org. Chem. Vol. 74, No. 8, 2009 3137

Podgorsˇek et al.
TABLE 4. Reactions of Aryl and Alkyl Iodine(III) Dichlorides
with 4-tert-Butylphenol (28)
TABLE 6. Reactions of Aryl and Alkyl Iodine(III) Dichlorides
with Acetophenone (32)
conditions
(time, h; T, °C)
conva
(%)
ratio
33/34
selectivity
33/34
reagent
reagent
conditions (time, h; T, °C)
conva (%)
8a, Ar3,4-Rf8
8b, Ar2,4-Rf6
8c, Ar2,4-Rf8
8d, Ar2,4-Rf10
9a, Rf8CH2
9b, Rf10CH2
16, Araq
26, rt
8, rt
67
76
78
74
78
67
80
65
79
49:51
69:31
72:28
61:39
70:30
72:28
95:5
0.97
2.26
2.57
1.55
2.34
2.57
19.00
1.50
3.00
8a, Ar3,4-Rf8
8b, Ar2,4-Rf6
8c, Ar2,4-Rf8
8d, Ar2,4-Rf10
9a, Rf8CH2
9b, Rf10CH2
16, Araq
24, rt
9, rt
24, 40
24, 40
8, 40
25, 40
24, rt
24, 75
8, rt
76
81
75
64
78
64
85
66
95
24, 40
8, 40
5, 40
24, 40
3, 0
18, Arsolid
20, Ar
24, 75
20, rt
60:40
75:25
18, Arsolid
20, Ar
a
1
Determined by H NMR spectroscopy.
a
1
Determined by H NMR spectroscopy.
acid (16) afforded the highest selectivity (95:5). Furthermore,
16 was completely consumed after only 3 h at 0 °C. When the
same reaction was repeated at room temperature, the selectivity
decreased to 80:20. The poorly soluble reagent Arsolid 18 was
again the least reactive. Extended periods at 75 °C were required
to achieve comparable conversions, and this was likely respon-
sible for the meager selectivity (60:40).
TABLE 5. Reactions of Aryl and Alkyl Iodine(III) Dichlorides
with Dibenzoylmethane (30)
reagent
conditions (time, h; T, °C)
conva (%)
8a, Ar3,4-Rf8
8b, Ar2,4-Rf6
8c, Ar2,4-Rf8
8d, Ar2,4-Rf10
9a, Rf8CH2
9b, Rf10CH2
16, Araq
26, rt
20, rt
24, 40
24, 40
6, 40
24, 40
3, 0
100
100
94
100
100
91
95
95
100
3. Conclusion
This study has established that the fluorous aryl and alkyl
iodine(III) dichlorides 8a-d and 9a,b are easily synthesized
by chlorinations of the corresponding aryl and alkyl iodides and
are effective and conveniently recycled chlorinating agents for
a variety of aliphatic and aromatic unsaturated organic sub-
strates. They can be isolated in yields ranging from 98% to 71%
(Table 1), for which we consider the precipitation conditions
amenable to further optimization. However, analogues of 9a,b
that lack or have longer methylene spacers are either not
accessible via chlorination or rapidly decompose at room
temperature (Scheme 3). We speculate in passing that it still
may be possible to access species of the type RfnICl2 via the
stable bis(trifluoroacetates) RfnI(OC(dO)CF3)2.11b,c The bis(ac-
etate) of the doubly ortho-substituted fluorous aryl iodide 4e
(Table 1), which also resists direct chlorination, is also easily
prepared.11a
18, Arsolid
20, Ar
24, 75
3, rt
a
1
Determined by H NMR spectroscopy.
products were detected. The fluorous reagents 8 and 9 showed
similar reactivity patterns as with anisole (25). Conversions with
the Rf10 species 8d and 9b were lower than those with the Rf8
analogues 8c and 9a. Chlorinations with Araq 16 and Arsolid
18required longer reaction times and/or higher temperatures.
The conversion with 20 was particularly high (95%), but as
with 16 and 18 a longer reaction time was required as
compared to Table 3.
The same series of reagents was next assayed for the
chlorination of the 1,3-diketone 30. As summarized in Table 5,
all afforded 2-chloro-1,3-diphenylpropane-1,3-dione (31) with
good conversions and selectivities. No dichlorinated product was
detected. The overall reactivity pattern was similar to those in
Tables 3 and 4. Among the fluorous reagents, the aliphatic
species Rf8CH2 9a again exhibited one of the higher reactivities.
But Araq 16 was distinctly more reactive, chlorinating 30 even
at 0 °C. The poorly soluble reagent 18 again needed higher
reaction temperatures for efficient conversion. As with 25 (Table
3), 20 gave the highest conversion.
Analogous chlorinations of acetophenone (32, Table 6)
afforded both monochlorinated and dichlorinated products (33,
34). With Ar3,4-Rf8 8a, 33 and 34 were obtained in almost equal
amounts. When ortho-substituted Ar2,4-Rf6 8b and Ar2,4-Rf8 8c
were used, selectivities for monochlorinated 33 increased to ca.
70:30. Very similar ratios were obtained with the fluorous alkyl
iodine(III) dichlorides 9. As in Table 3, 3-(dichloroiodo)benzoic
Among the aromatic fluorous reagents, 8a,b generally show
the highest reactivity. This may be due to the lack of an ortho
substituent in 8a, and the greater solubility of 8b vs 8c,d. The
aliphatic fluorous reagents 9a,b are also less reactive, but all
substrates investigated can be chlorinated with all of the fluorous
iodine(III) reagents on convenient time scales between room
temperature and 40 °C. One advantage of the ortho-substituted
reagents is the higher selectivities in Tables 3 and 6. The
recoveries of the fluorous iodide coproducts per Scheme 4 are
uniformly high (97-90%). Overall, we judge the best combina-
tion of performance characteristics to be found with 8c and 9a.
This work also significantly extends past studies with the
nonfluorous recyclable aryl iodine(III) reagents Araq 16 and
Arsolid 18 (Table 1), providing the first simple mono- and di-
chlorinations. The complementary protocols in Schemes 5 and
6 return the aryl iodide coproducts in 91-85% and 91-89%
yields, respectively. We do not view these yield ranges as much
different than those with the fluorous iodides. Nonetheless,
3138 J. Org. Chem. Vol. 74, No. 8, 2009

Fluorous and Nonfluorous Aryl and Alkyl Iodine(III) Dichlorides
(s), 1189 (s), 1143 (s), 1119 (s), 1077 (w), 1015 (m), 810 (m), 791
(m). MS (FAB): 798 (70) [3b]+, 451 (100) [3b - CH2CH2Rf6]+.
2,4-(Rf6(CH2)3)2C6H3I (4b). A flask was charged with 3b (8.853
g, 11.09 mmol), I2 (11.1 g, 44.0 mmol), H5IO6 (9.50 g, 42.0 mmol),
and a mixture of H2SO4, acetic acid, and water (3:100:20 v/v/v,
100 mL). The mixture was stirred overnight at 65 °C and cooled
to room temperature. Water (100 mL) and ether (500 mL) were
added. The organic phase was separated, washed with aqueous
Na2S2O3 (1.0 M, 200 mL), and dried (MgSO4). After solvent
removal, hexane/CH2Cl2 (1:1 v/v) was added, and the mixture was
filtered through a silica gel plug. The solvent was removed from
the filtrate by rotary evaporation to give 4b as a yellow solid (7.690
g, 8.32 mmol, 75%). Mp (capillary): 31.5-31.8 °C. Anal. Calcd
unless multirun averaging and/or optimization were to alter this
picture, a slight recycling edge seems to lie with the fluorous
reagents. Of course, the traditional reagent (dichloroiodo)ben-
zene (Ar 20), for which the coproduct must be recovered
chromatographically from the reactions in Tables 2-6, is not
competitive with any of these.
The reactivities of Araq 16, Arsolid 18, and Ar 20 provide a
number of interesting contrasts with the fluorous reagents. In
general, the carboxylic acid containing reagent Araq 16 is the
most reactive (Tables 2, 3, 5, 6). Often Ar 20 is the next most
reactive (Tables 2, 3, 5), and edges out Araq 16 in Table 4. The
reactivity of poorly soluble Arsolid 18 generally parallels that of
the least soluble fluorous reagents, but can be much lower
(Tables 4-6). This is clearly the least promising reagent for
further development. In the two reactions that give product
mixtures (Tables 3, 6) Araq 16 also provides the highest
selectivities, perhaps in part as it can be employed at lower
temperatures.
1
for C24H15F26I: C, 31.17; H, 1.62. Found: C, 31.29; H, 1.83. H
NMR (400 MHz, CDCl3): δ ) 7.75 (d, 3JHH ) 8 Hz, 1H), 7.03 (s,
3
3
1H), 6.76 (d, JHH ) 8 Hz, 1H), 2.96, 2.67 (2t, JHH ) 8 Hz, 4H),
2.19-1.88 (m, 8H). 13C{1H} NMR (100 MHz, CDCl3): δ ) 143.5,
141.3, 140.0, 129.5, 128.4, 97.5, 39.7, 34.4, 30.1-30.0 (apparent
m), 21.7, 20.8. IR (oil film, cm-1): 2957 (w), 2872 (w), 2347 (w),
1463 (w), 1366 (w), 1320 (w), 1231 (s), 1189 (s), 1143 (s), 1119
(s), 1077 (m), 1011 (m), 845 (m). MS (EI): 924 (100) [4b]+, 923
(80) [4b - H]+, 797 (20) [4b - I], 703 (80), 577 (40).
In summary, this work has contributed to the development
of both hypervalent iodine and green chemistry through the
synthesis of new fluorous aryl and alkyl iodine(III) dichlorides
that are effective and easily recyclable chlorinating agents and
by careful comparisons to known nonfluorous analogues that
can be recycled by alternative protocols. Additional efforts
involving recyclable reagents and catalysts are underway in all
of the authors’ laboratories and will be reported in due course.
2,4-(Rf6(CH2)3)2C6H3ICl2 (8b). Hexane (40 mL), 4b (0.924 g,
1.00 mmol), and chlorine were combined in a procedure analogous
to that for 8a. An identical workup gave 8b as a yellow solid (0.706
g, 0.71 mmol, 71%). Mp (capillary): 68-70 °C. Iodometric titration:
99% purity. Anal. Calcd for C24H15Cl2F26I: C, 28.97; H, 1.52.
1
Found: C, 29.32; H, 1.43. H NMR (300 MHz, CDCl3): δ ) 8.20
(d, 3JHH ) 8.4 Hz, 1H), 7.29 (d, 4JHH ) 2.2 Hz, 1H), 7.14 (dd, 3JHH
4
3
) 8.4 Hz, JHH ) 2.2 Hz, 1H), 3.19 (t, JHH ) 7.5 Hz, 2H), 2.81
(t, JHH ) 7.7 Hz, 2H), 1.92-2.35 (m, 8H). 13C{1H} NMR (76
3
4. Experimental Section
MHz, CDCl3): δ ) 147.2, 141.2, 137.3, 130.3, 130.2, 38.3, 34.8,
30.3 (t, 2JCF ) 22 Hz), 21.7, 21.3. 19F NMR (282 MHz, CDCl3): δ
4.1. Representative Synthesis of a Fluorous Aryl Iodine(III)
Dichloride 8 (Others Are Supplied in the Supporting Informa-
tion). 1,3-(Rf6CH2CHdCH)2C6H4 (2b). A three-necked flask was
charged with (Rf6CH2CH2)Ph3P+I- (22.32 g, 30.5 mmol),20 K2CO3
(8.28 g 60.0 mmol), isophthalaldehyde (1.97 g, 14.7 mmol),
p-dioxane (200 mL), and distilled water (0.6 mL). The mixture was
stirred overnight at 95 °C and cooled to room temperature. All
volatiles were removed by rotary evaporation. Then CH2Cl2 (200
mL) and water (200 mL) were added. The organic phase was
separated and dried (MgSO4). The solvent was removed by rotary
evaporation, and the residue was dissolved in petroleum ether and
chromatographed (silica gel column, CH2Cl2/hexane, 1:1 v/v,
Rf(TLC) ) 0.95). The solvent was removed from the product
containing fractions by rotary evaporation to give 2b as a yellow
oil of moderate purity (9.087 g, 11.44 mmol, 78%). 1H NMR (400
MHz, CDCl3): δ ) 7.38-7.36 (m, 1H), 7.16-7.14 (m, 2H),
7.07-7.05 (m, 1H), 6.84-6.81 (m, 2H), 5.80-5.77 (m, 2H),
3.13-2.92 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3): δ ) 136.2,
3
) -81.4 (t, JFF ) 10 Hz, 6F), -114.6 (m, 4F), -122.4 (m, 4F),
-123.4 (m, 4F), -123.9 (m, 4F), -126.7 (m, 4F).
4.2. Representative Synthesis of a Fluorous Alkyl Iodine(III)
Dichloride 9. Rf10CH2OSO2CF3 (6b). A three-necked flask was
fitted with a nitrogen inlet and dropping funnel and charged with
Rf10CH2OH (5b; 5.107 g, 9.29 mmol), pyridine (1.12 g, 1.15 mL,
14.0 mmol), and CF3C6H5 (50 mL) under nitrogen. The flask was
cooled to 0 °C, and after 30 min, (CF3SO2)2O (4.23 g, 3.44 mL,
15.0 mmol) was slowly added. The cold bath was removed, and
the light red suspension was stirred overnight. Water was added
(60 mL), and the organic phase was separated and dried (MgSO4).
The solvent was removed by rotary evaporation, and the solid
residue was dissolved in petroleum ether and chromatographed
(silica gel column, petroleum ether/ethyl acetate, 4:1 v/v, Rf (TLC)
) 0.95). The solvent was removed from the product containing
fractions by rotary evaporation to give 6b as a white solid (6.261
g, 9.18 mmol, 99%). Mp (capillary): 84.4 °C. Anal. Calcd for
C12H2F24O3S: C, 21.11; H, 0.29; S, 4.69. Found: C, 20.60; H, 0.35;
3
2
135.1, 128.7, 128.2, 127.6, 118.4 (t, JCF ) 4 Hz), 30.6 (t, JCF
)
23 Hz). IR (oil film, cm-1): 3038 (w), 2347 (w), 1447 (w), 1200
(s), 1146 (s), 969 (w), 899 (m), 814 (w).
1
3
S, 4.87. H NMR (400 MHz, acetone-d6): δ ) 5.52 (t, JHF ) 15
Hz, 2H). 13C{1H} NMR (100 MHz, C6F14, internal lock C6D6): δ
) 71.0 (t, 2JCF ) 27 Hz). IR (powder film, cm-1): 2961 (w), 2926
(w), 2856 (w), 1420 (m), 1204 (s), 1139 (s), 1081 (w), 1027 (m),
883 (m), 822 (m). MS (EI): 663 (15) [6b - HF]+, 613 (30), 549
(15), 511 (35), 463 (100).
1,3-(Rf6(CH2)3)2C6H4 (3b). A round-bottom flask with a gas inlet
was charged with Pd/C 10% (0.400 g, 0.37 mmol), 2b (9.087 g,
11.44 mmol), hexane (35 mL), and ethanol (35 mL). The mixture
was flushed with hydrogen and connected to a thick-walled
hydrogen balloon with a PVC hose. The mixture was stirred at
room temperature overnight and then filtered through a plug of
Celite. The plug was washed with hexane (80 mL). The filtrate
was concentrated, and CH2Cl2/hexane (1:1 v/v) was added. The
sample was filtered through a silica gel plug. The solvent was
removed by rotary evaporation to give 3b as a clear oil (8.853 g,
11.09 mmol, 97%). Anal. Calcd for C24H16F26: C, 36.09; H, 2.01.
Found: C, 35.80; H, 1.99. 1H NMR (400 MHz, CDCl3): δ )
7.28-7.24 (m, 1H), 7.06-7.00 (m, 3H), 2.72-2.69 (m, 4H),
2.08-1.95 (m, 8H). 13C{1H} NMR (100 MHz, CDCl3): δ ) 140.9,
128.8, 128.4, 126.4, 34.9, 30.2 (t, 2JCF ) 23 Hz), 21.8. IR (oil film,
cm-1): 2961 (w), 2347 (w), 1467 (w), 1366 (w), 1316 (w), 1231
Rf10CH2I (7b). A flask was charged with 6b (6.261 g, 9.18
mmol), KI (7.60 g, 45.78 mmol), and ethylene glycol (35 mL).
The mixture was refluxed at 200 °C overnight and allowed to cool
to room temperature. Water (100 mL) and hexane (40 mL) were
added. The organic phase was separated and dried (MgSO4). The
solvent was removed by rotary evaporation. The white solid was
dissolved in petroleum ether and chromatographed (silica gel
column, petroleum ether/ethyl acetate, 20:1 v/v). The solvent was
removed from the product containing fractions by rotary evaporation
to give 7b as a white solid (5.297 g, 8.03 mmol, 87%). Mp
(capillary): 80.8 °C. Anal. Calcd for C11H2F21I: C, 20.00; H, 0.30.
1
Found: C, 20.05; H, 0.49. H NMR (400 MHz, acetone-d6): δ )
J. Org. Chem. Vol. 74, No. 8, 2009 3139

Podgorsˇek et al.
4.06 (t, 3JHF ) 18 Hz, 2H). 13C{1H} NMR (100 MHz, acetone-d6):
comparisons with literature data (see the Supporting Information)
or commercial samples (for 26 and 27).
2
δ ) -2.79 (t, JCF ) 25 Hz). IR (powder film, cm-1): 1420 (w),
Liquid/Liquid Fluorous/Organic Phase Separation for Chlo-
rination Using Fluorous Iodine(III) Dichlorides (8 and 9).
Perfluorohexane (2 mL) and 80-90% aqueous methanol (2 mL)
were added to the reaction mixture. The fluorous and organic phases
were separated, and the fluorous phase was further washed with
80-90% aqueous methanol (3 × 2 mL). The combined methanol/
H2O phases were extracted with hexane (3 × 3 mL). The solvent
was removed from the combined extracts by rotary evaporation,
and the crude chlorination product was analyzed by 1H NMR
spectroscopy. Evaporation of the perfluorohexane from the fluorous
phase gave the fluorous iodides 4 and 7 in 90-97% yields. The
perfluorohexane was recovered and reused as well.
1374 (w), 1343 (w), 1204 (s), 1146 (s), 1069 (w), 1046 (m), 891
(m).
Rf10CH2ICl2 (9b). Hexane (30 mL), Rf10CH2I (7b; 0.660 g, 1.00
mmol), CF3SO3H (0.026 mL, 0.30 mmol), and Cl2 were combined
in a procedure analogous to that for 9a. An identical workup gave
9b as a yellow solid (0.614 g, 0.84 mmol, 84%). Mp (capillary):
135-138 °C. Since 9b was insoluble in all common solvents, it
could not be characterized by NMR. Iodometric titration: 98%
purity. Anal. Calcd for C11H2Cl2F21I: C, 18.08; H, 0.28. Found: C,
18.36; H, 0.33.
4.3. Generation of Rf8CH2CH2ICl2 (12). Chlorination of
Rf8CH2CH2I (11). A flask was charged with acetonitrile (10 mL)
and 11 (0.574 g, 1.00 mmol) and cooled to 0 °C. The mixture was
saturated with molecular chlorine with stirring. When the sample
was warmed to room temperature, rapid decomposition of
Rf8CH2CH2ICl2 (12) was observed with evolution of brown gaseous
iodine chloride. After 2 h, the acetonitrile was removed under
Liquid/Liquid Organic/Aqueous Phase Separation for Chlo-
rination Using m-HOOCC6H4ICl2 (16). The reaction mixture was
transferred to a separatory funnel, and 5% aqueous NaHCO3 (5
mL) was added. The product was extracted with petroleum ether
(3 × 3 mL). The solvent was removed from the combined extracts
by rotary evaporation and the crude chlorination product analyzed
1
reduced pressure. H NMR (300 MHz, CDCl3) analysis revealed
1
by H NMR. The aqueous phase was acidified with 5% aqueous
the formation of Rf8CH2CH2Cl (21): δ ) 3.70-3.75 (m, 2H),
HCl (15 mL). The white precipitate was isolated by filtration and
air-dried to give 15 in 85-91% yields.
3.22-3.28 (m, 2H).22
Trapping of Rf8CH2CH2ICl2 (12). A flask was charged with
Rf8CH2CH2I (11; 0.574 g, 1.00 mmol) and acetonitrile (10 mL).
The solution was cooled to 0 °C and saturated with Cl2 with stirring.
Over the course of 15 min, a brown solution was obtained. Then
cyclooctene (22; 0.110 g, 1.00 mmol) was added and the mixture
decolorized. After 30 min, the acetonitrile was evaporated under
reduced pressure. NMR analysis revealed the formation of trans-
1-chloro-2-iodocyclooctane (24) as the sole product. 1H NMR (300
Solid/Liquid Biphase Separation for Chlorination Using
4,4′-Cl2IC6H4C6H4ICl2 (18). Methanol was added to the reaction
mixture, and the pale yellow precipitate was isolated by filtration
and air-dried to give 4,4′-diiodobiphenyl (17) in 89-91% yields.
The methanol was evaporated under reduced pressure, and the crude
1
chlorination product was analyzed by H NMR.
Acknowledgment. This research has been supported by the
Ministry of Higher Education, Science and Technology of the
Republic of Slovenia, the Young Researcher Program (A.P.)
of the Republic of Slovenia, Deutsche Forschungsgemeinschaft
(DFG, GL 300/3-3), the Welch Foundation, and the European
Union (COST D29 working group 0011-03). We are grateful
to the National NMR Centre at the National Institute of
Chemistry in Ljubljana, the Mass Spectroscopy Centre at the
JSI, and Faculty of Chemistry and Chemical Technology
University of Ljubljana for elemental analyses (T. Stipanovicˇ
and B. Stanovnik).
3
MHz, CDCl3): δ ) 4.60 (ddd, JHH ) 9.0, 7.0, 2.3 Hz, 1H), 4.47
(ddd, 3JHH ) 9.0, 7.4, 1.7 Hz, 1H), 1.95-2.15 (m, 2H), 2.22-2.41
(m, 2H), 1.38-1.91 (m, 8H). 13C{1H} NMR (76 MHz; CDCl3;
Me4Si): δ ) 70.1, 41.9, 34.5, 33.2, 27.9, 25.6, 25.2, 25.1.
Compound 24 is unstable and decomposes during the purification
procedure. Its structure was confirmed by comparison of 1H NMR
chemical shifts of independently prepared sample by reaction of
cyclooctene (22) with ICl in CH3CN.
4.4. Typical Procedure for the Chlorination of 22, 25, 28,
30, and 32 Using the Aryl and Alkyl Iodine(III) Dichlorides
8, 9, 16, 18, and 20. The iodine(III) dichloride (0.10 mmol) was
added to 0.10 mmol of the substrate in 1 mL of acetonitrile. As
summarized in Tables 2-6, the mixture was stirred at 0-70 °C
for 0.5-26 h. The progress of the reaction was monitored by TLC.
When the iodine(III) dichloride was consumed, the acetonitrile was
evaporated under reduced pressure. Substrate conversions were
determined by redissolving the samples in CDCl3 and integrating
characteristic substrate and product signals. Subsequent workup
depended upon the chlorinating reagent as detailed below. The
identities of the chlorinated products were confirmed by NMR and
Supporting Information Available: Additional experimental
procedures for syntheses of analogues of the compounds in
sections 4.1 and 4.2 and nonfluorous aryl iodine(III) dichlorides,
spectroscopic data of chlorinated products, and copies of NMR
spectra for all new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO900233H
3140 J. Org. Chem. Vol. 74, No. 8, 2009