Iodination of alcohols under microwave irradiation using KI in the presence of a catalytic amount of ionic liquid triethylamoniom hydrogensulfate([Et 3NH]+HSO4-)

Article abstract of DOI:10.1080/00397910802120916

The iodination of alcohols with KI in the presence of a catalytic amount of triethylamoniom hydrogensulfate ([Et₃NH]⁺HSO ₄^-) as a novel and inexpensive ionic liquid under microwave irradiation has been investigated. Copyright Taylor & Francis Group, LLC.

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Iodination of Alcohols Under
Microwave Irradiation Using
KI in the Presence of a
Catalytic Amount of Ionic
Liquid Triethylamoniom
Hydrogensulfate( )
Abdol R. Hajipour a , Ghobad Azizi b & Arnold E.
Ruoho a
a Department of Pharmacology, University of
Wisconsin, Medical School, Madison, Wisconsin, USA
b Department of Chemistry, Isfahan University of
Technology, Isfahan, Iran
Version of record first published: 22 Dec 2008.
To cite this article: Abdol R. Hajipour , Ghobad Azizi & Arnold E. Ruoho (2008):
Iodination of Alcohols Under Microwave Irradiation Using KI in the Presence of a
Catalytic Amount of Ionic Liquid Triethylamoniom Hydrogensulfate( ), Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:2, 242-250
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Synthetic Communications1, 39: 242–250, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802120916
Iodination of Alcohols Under Microwave
Irradiation Using KI in the Presence of a
Catalytic Amount of Ionic Liquid
Triethylamoniomþ
Hydrogensulfate(½Et3NHꢀ HSOꢁ4 )
Abdol R. Hajipour,1 Ghobad Azizi,2 and Arnold E. Ruoho1
1Department of Pharmacology, University of Wisconsin, Medical School,
Madison, Wisconsin, USA
2Department of Chemistry, Isfahan University of Technology, Isfahan, Iran
Abstract: The iodination of alcohols with KI in theþ presence of a catalytic
amount of triethylamoniom hydrogensulfate (½Et3NHꢀ HSOꢁ4 ) as a novel and
inexpensive ionic liquid under microwave irradiation has been investigated.
Keywords: Acidic ionic liquid, alkyl iodide, iodination of alcohols, KI, triethyla-
moniom hydrogensulfate
INTRODUCTION
Alkyl halides are very useful intermediates in organic synthesis. They
react with nucleophiles such as amines or alkoxides to give the corre-
sponding amines or ethers and can be lithiated to introduce electrophiles
via a halogen–lithium exchange reaction. The most common precursors
for preparation of alkyl halides are alcohols, and their conversion into
halides is one of the most frequently used functional group transform-
ation reactions.[1] Although alkyl iodides are less stable and more expens-
ive than other alkyl halides, they are more reactive than the other
halogens, and in some cases iodides are the only reactive halides. For
converting alcohols to the corresponding alkyl idodides, several methods
Received February 9, 2008
Address correspondence to Abdol R. Hajipour, Department of Chemistry, Isfahan
University of Technology, Isfahan 84156, IR, Iran. E-mail: haji@cc.iut.ac.ir
242

Iodination of Alcohols Using Microwaves
243
have been described using a variety of reagent systems such as BF3-Et2O=
KI,[2] P4=I2,[3] Cl2SO–DMF=KI,[4] MgI2,[5] ClSiMe3=KI,[6] R3PI2–Et2O,
C6H6=HMPA,[7] CeCl3 ꢀ 7H2O=KI,[1] PPh3=DDQ=R4NþXꢁ,[8] KI=
BF3 ꢀ Et2O,[9] and PPh3=DEAD=LiI.[10] Other useful methods including
applying KI in the presence of phase-transfer catalysts[11] and=or I2=
petroleum ether.[12] KI=Amberlyst 15[13] and polymer-supported
triphenylphosphine=I2=ImH have also been reported for iodination of
benzylic alcohols.[14] However, some of the reported systems suffer from
drawbacks such as the danger of explosion (DEAD),[15] low yields,[11,12]
long reaction times,[1,12] harsh reaction conditions, noncommercially
available materials, and tedious workup procedures.[11] Thus new
methods, with higher efficiency higher selectivity, less toxicity, and that
use commercially available materials, are important.
Recently, room-temperature ionic liquids (RTILs) have received
much attention because of their excellent properties and potential appli-
cation in many fields. Ren and Wu[16] have demonstrated that by employ-
ing 1,3-dialkylimidazolium halide-based ionic liquids, it is possible to
convert alcohols to alkyl halides in the presence of either an organic or
inorganic acid. However, reaction times are very long (24 and 48 h).
RESULTS AND DISCUSSION
In continuation of our effort to develop a mild procedure for organic
functional group transformation,[17–21] here we report a novel application
of RTILS for selective iodination of alcohols using KI under solvent-free
conditions with microwave (MW) irradiation in short reaction times and
high yields (Scheme 1).
Triethylamoniom hydrogensulfate ½Et3NHꢂþ½HSO4ꢂꢁ is an efficient
RTIL that can be used as an alternative for other mineral acids such as
H2SO4 and HCl for conversion of benzyl alcohols into the corresponding
benzyl iodides. To optimize the reaction conditions for iodination of
benzyl alcohol to the corresponding benzyl iodide, we tried different
Scheme 1. Iodination of alcohols with acidic ionic liquid under microwave
irradiation.

244
A. R. Hajipour, G. Azizi, and A. E. Ruoho
conditions. Initially we examined a mixture containing 1 mmol of benzyl
alcohol, 0.05 g of ionic liquid, and 1 mmol of KI in CH3CN at room
temperature. After 10 h of stirring, no reaction was occurred at all;
however, reaction mixture was converted to benzyl in 80% yields after
4 h of refluxing. By grinding a mixture of benzyl alcohol and KI in the
presence of catalytic amounts of ½Et3NHꢂþ½HSO4ꢂꢁ as an acid catalyst
by a pestle, the reaction time for iodination was reduced to 2 h with
90% conversion. Under microwave irradiation, the benzyl alcohol was
converted to benzyl iodide in quantitative yields after 60 s. Therefore,
based on the optimized conditions, several alcohols were iodinated
(Table 1).
To optimize the amount of ionic liquid, 1 mmol of benzyl alcohol and
1 mmol of KI were treated in the presence of different amounts of ionic
liquid using microwave irradiation (200 W). As showing in Fig. 1,
20 mmol% ionic liquid as acid catalyst gave the best conversion.
The power for iodination of 4-nitrobenzyl alcohol was reduced to
100 W. This may be due to the polar NO2 substituent, which absorbs
microwave irradiation; at the higher powers, the reaction mixture was
incinerated. On the other hand, in the case of secondary alcohols, the
conversion into corresponding iodides needed longer reaction times
(entries l, m, and n). The reaction was found to be highly selective only
for allylic and benzylic alcohols, and saturated aliphatic alcohols
were not iodinated even after a prolonged reaction time. By this method,
secondary allylic or benzylic alcohols also were easily converted to the
corresponding allylic or benzylic iodide in high yields.
The possible mechanism for this transformation is outlined in
Scheme 2. The acidic ionic liquid (½Et3HꢂþHSO4ꢁ) protonated the oxygen
of alcohol to form a good leaving group for nucleophilic substitution of
iodide.
To evaluate the chemoselectivity of this method, we studied the
competitive reactions. As shown in Table 2, entries 1 and 2, when we
treated a mixture of benzylic aþnd saturated alcohols in the presence of
catalytic amounts of ½Et3Hꢂ HSOꢁ4 , only benzylic alcohols were
iodinated. In competition between the benzyl and 4-nitrobenzyl alcohol,
the 4-nitrobenzyl alcohol was intact and only the benzyl alcohol was
iodinated (Table 2, entry 3).
CONCLUSION
In conclusion, the present study shows that this procedure is a valuable
alternative for conversion of alcohols into iodo derivatives under
solvent-free conditions with high yield in short reaction times. The

Iodination of Alcohols Using Microwaves
245
Table 1. Conversion of alcohols to the corresponding iodides using
½Et3NHꢂþ½HSO4ꢂꢁ under microwave irradiation
Entry
Substrate
Product
Time (s)
Yielda (%)
a
60
95
b
90
90
c
60
90
86
80
d
e
f
30
40
98
93
g
h
i
80
94
50
92
60
86
j
50
90
k
> 120
50b
l
100
120
100
91
70
m
n
93
(Continued)

246
A. R. Hajipour, G. Azizi, and A. E. Ruoho
Table 1. Continued
Entry
o
Substrate
Product
Time (s)
40
Yielda (%)
90
p
q
120
120
—
—
aYields refer to pure isolated products and were characterized by comparison of
1
their physical and spectral data (IR, H NMR) with authentic samples.
bPower was 100 W.
straightforward procedure, inexpensive reagents, and short reaction times
are advantages of the present method over reported methods.
EXPERIMENTAL
General
All reagents were purchased from Merck and Aldrich and used without
further purification. All yields refer to isolated products after
purification. Products were characterized by comparison with authentic
1
samples and by spectroscopic data (IR, H NMR, and MS analysis).
1H NMR spectra were recorded at 300 MHz in CDCl3, relative to
TMS (0.00 ppm). All of the reactions were carried out using a Milestone
microwave oven (MicroSYNTH).
Figure 1. Optimization of the amount of ionic liquid.

Iodination of Alcohols Using Microwaves
247
Scheme 2. Proposed mechanism for transformation of alcohols into iodo
compounds.
Preparation of ½Et3HꢂþHSO4ꢁ
Triethylamine (2.8 mL, 20 mmol) was dissolved in dichloromethane
(10 mL), and 1 mL of concentrated H2SO4 (20 mmol) was added slowly
at 0ꢃC. The reaction mixture was stirred at room temperature for 30 min.
min. The resulting ionic liquid was washed by diethyl ether and dried in a
vacuum at 80ꢃC. Yield 100%, IR (KBr): 3450, 2978, 2944, 2734, 2600,
.
2494, 1650, 1481, 1398, 1171, 1038, 850 cmꢁ1 1H NMR (300 MHz,
CDCl3): d 9.7 (s, 1 H), 9.35 (s, 1 H), 3.3 (q, 2 H), 1.8 (t, 3 H) ppm.
13C NMR (D2O, 500 MHz): d 9 (CH3), 470 (CH2) ppm.
Iodination of Benzyl Alcohol (Typical Procedure)
In a mortar, a mixture of benzyl alcohol (1 mmol, 0.11 g), KI (1.0 mmol,
0.15 g), and triethylamoniom hydrogensulfate (0.2 mmol, 0.04 g) was
ground with a pestle (30 s) to a homogeneous mixture. The mortar was
put in a sealed Teflon1 vessel, and the reaction mixture was irradiated
for the time specified in Table 1. Thin-layer chromatography (TLC)
Table 2. Competitive reaction for selective iodination of different alcoholsa
aThe progress of the reaction was determined by GC and TLC analysis.

248
A. R. Hajipour, G. Azizi, and A. E. Ruoho
monitored the progress of the reaction. After disappearance of the
alcohol (n-hexane–EtOAc, 75:25) the reaction mixture was diluted with
dichloromethane (25 mL). The organic layer was washed with an aqueous
solution of Na2S2O3 (10%, 10 mL), and then H2O (2 ꢄ 10 mL). The
organic layer was dried over anhydrous Na2SO4. The solvent was evapo-
rated under reduced pressure, and the residue was purified by short-
column chromatography (n-hexane–EtOAc, 80:20). Benzyl iodide was
obtained in 95% yield (0.209 g). IR (neat) cmꢁ1: 3010, 2930, 1595,
1
1485, 1430, 1070, 835, 750, 660. H NMR (300 MHz, CDCl3, TMS) d
7.3–7.0 (m, 5H), 3.95 (s, 2H).
Competitive Reaction for Iodination of 4-Nitrobenzyl Alcohol in the
Presence of Benzyl Alcohol (Typical Procedure)
In a mortar, a mixture of 4-nitrobenzyl alcohol (1 mmol, 0. 26 g), benzyl
alcohol (1 mmol, 0.11 g), and triethylamoniom hydrogensulfate
(0.2 mmol, 0.04 g) was ground with a pestle to obtain a homogeneous
mixture. The mortar was put in a sealed Teflon1 vessel, and the reaction
mixture was irradiated for 60 s by microwave. TLC monitored the
progress of the reaction. Benzyl iodide was obtained in 93% yield, and
4- nitrobenzyl alcohol was intact (Table 2, entry 1).
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