Efficient method for iodination of alcohols using KI/silica sulfuric acid (SSA)

Article abstract of DOI:10.1080/00397910500503421

A straightforward and effective procedure for the conversion of benzylic and allylic alcohols to the corresponding iodides using KI/SSA in acetonitrile at room temperature. Copyright Taylor & Francis Group, LLC.

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Efficient Method for Iodination of Alcohols
using KI/Silica Sulfuric Acid (SSA)
a b
b
a
Abdol R. Hajipour
, Amin Zarei & Aronold E. Ruoho
a
Department of Pharmacology , University of Wisconsin, Medical School ,
Madison, Wisconsin, USA
b
Pharmaceutical Research Laboratory, Department of Chemistry , Isfahan
University of Technology , Isfahan, Iran
Published online: 16 Aug 2006.
To cite this article: Abdol R. Hajipour , Amin Zarei & Aronold E. Ruoho (2006) Efficient Method for Iodination
of Alcohols using KI/Silica Sulfuric Acid (SSA), Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 36:8, 1039-1050, DOI: 10.1080/00397910500503421
To link to this article: http://dx.doi.org/10.1080/00397910500503421
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Synthetic Communications , 36: 1039–1050, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500503421
Efficient Method for Iodination of Alcohols
using KI/Silica Sulfuric Acid (SSA)
Abdol R. Hajipour
Department of Pharmacology, University of Wisconsin, Medical School,
Madison, Wisconsin, USA and Pharmaceutical Research Laboratory,
Department of Chemistry, Isfahan University of Technology, Isfahan,
Iran
Amin Zarei
Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan
University of Technology, Isfahan, Iran
Aronold E. Ruoho
Department of Pharmacology, University of Wisconsin, Medical School,
Madison, Wisconsin, USA
Abstract: A straightforward and effective procedure for the conversion of benzylic and
allylic alcohols to the corresponding iodides using KI/SSA in acetonitrile at room
temperature.
Keywords: Alcohols, iodination, potassium iodide, silica sulfuric acid
INTRODUCTION
[1]
Organic halides are very useful intermediates in organic synthesis. They
react with nucleophiles such as amines or alkoxides to give the corresponding
substituted products and can be lithiated to introduce electrophiles via a
[
2]
halogen–lithium exchange reaction. Alkyl iodides or bromides are widely
Received in the U.K. July 6, 2005
Address correspondence to Abdol R. Hajipour, Department of Pharmacology,
University of Wisconsin, Medical School, 1300 University Avenue, Madison, WI
53706-1532, USA. E-mail: haji@cc.iut.ac.ir
1
039

1
040
A. R. Hajipour et al.
used for ionic and radical carbon–carbon coupling reactions and also act as
intermediates in substitution, elimination, and rearrangement reactions.
Alkyl iodides are less stable than the corresponding chloride or bromide
and more reactive than the other halides, and in some cases iodides are the
[
3]
only reactive halides. The most common precursors to alkyl halides are
alcohols, and their conversion into iodides is one of the most frequently
[4]
used functional-group transformation reactions.
To perform iodination of hydroxyl groups, several methods have been
[
5]
described using a variety of reagent systems such as BF Et O/NaI,
3
2
[
6]
[7]
[8]
[9]
[10]
[11]
P I ,
2
P /I ,
2
Cl SODMF/KI,
2
MgI2,
HI,
CeCl 7H O/NaI,
ClSiMe /NaI,
3
4
4
[12]
[13]
.
R PI Et O, or C H /HMPA,
3
PPh /DDQ/
3
2
2
2 [14]
6
6
3
[16]
2
þ
[15]
[17]
.
KI/BF Et O,
R N X ,
4
ZrCl /NaI,
I2/petroleum ether,
Polymer-supported triphenylphosphine/I /ImH has also
NaI/
3
2
4
[
18]
amberlyst 15.
been used for the iodination of benzylic alcohols.
2
[19]
Although some of
these methods have convenient protocols with good to high yields, the
majority of these methods suffer from drawbacks such as the presence of
hazardous vapor, high temperature, long reaction times, moisture sensitivity
of the reagents, low yields, harsh reaction conditions, noncommercially
available materials, and tedious workup procedures. Introducing new
methods with higher efficiency and selectivity, less toxicity, and easy
handling, and which use inexpensive and commercially available materials,
is important.
RESULTS AND DISCUSSION
In a continuation of our studies on the application of solid acids, we found that
silica sulfuric acid (SSA) (I) has many advantages over sulfuric acid. This
reagent is safe, easy handled, and environmentally benign, and presents
fewer disposal problems. Therefore, SSA can be an excellent candidate for
[20]
sulfuric acid replacement in organic reactions.
In this article we report an efficient and mild procedure for iodination of
alcohols using a combination of SSA and potassium iodide under hetero-
geneous conditions (Scheme 1).
Scheme 1.

Efficient Method for Iodination of Alcohols
1041
The iodination of benzyl alcohol was selected for optimization of the
reaction conditions. Initially we studied the conversion of benzyl alcohol
(1 mmol, 0.1 mL) to benzyl iodide with SSA (1.2 mmol, 0.35 g) and
potassium iodide (1.2 mmol, 0.2 g) in the presence of various solvents and
also under solvent-free conditions (grinding). As shown in Table 1, in com-
parison to other conditions the reaction proceeds rapidly in acetonitrile and
gives optimal yield. Therefore, we investigated the iodination of various
benzylic and allylic alcohols in the presence of SSA and potassium iodide
in acetonitrile at room temperature (Table 2). It was also observed that
when benzyl alcohol was treated with KI without SSA, no change took
place at all, implying that SSA plays an important role in this reaction.
A variety of benzylic and allylic alcohols were smoothly converted to the
corresponding iodides using the KI/SSA system at room temperature. The
reactions are highly selective for the conversion of benzylic and allylic
alcohols to the corresponding iodides in good to high yields (Table 2). In
the case of phenol and saturated alcohols, the conversion into the correspond-
ing iodides was not carried out even after prolonged stirring in acetonitrile
(Table 2, entries 19–23). We also studied other solid supports such as SiO2,
Al O , zeolite HZSM-5, and montmorillonite K10 for this conversion. As
2
3
shown in Table 2 (entries 2–5), conversions of benzyl alcohol to benzyl
iodide with KI/SiO , KI/Al O , KI/montmorillonite K10, and KI/HZSM-5
2
2 3
were carried out in low yields. Furthermore, we investigated various
benzylic alcohols with both electron-donating and electron-withdrawing
groups on the aryl ring. The reaction is slightly accelerated by an electron-
donating group (Table 2, entries 6–10), and the substitution of the electron-
withdrawing group on the aromatic ring retards the transformation (Table 2,
entries 11–16).
To evaluate the chemoselectivity of this method, we studied competitive
reactions for the iodination of benzylic alcohols in the presence of phenol and
saturated alcohols. The remarkable selectivity of these reactions allowed only
Table 1. Conversion of benzyl alcohol to benzyl iodide under
different conditions using KI/SSA
c
Solvent
Time
Benzyl iodide (%)
a
Acetonitrile
Ethyl acetate
1.5 h
5 h
85
40
25
35
70
55
a
a
Diethyl ether
a
THF
Dichloromethane
5 h
5 h
a
1.5 h
10 min
b
None
a
Stirring at room temperature in 5 mL of solvents.
Grinding at room temperature.
b
c
Yields refer to isolated pure products.

a,b
Table 2. Conversion of alcohols to iodides using KI/ SSA at room temperature
Time
(h)
Yield
(%)
Entry
1
Substrate
Reagent
Product
KI, SSA
1.5
5
85
10
5
2
3
4
5
6
KI, SiO2
KI, Al
2
O
3
5
KI, Montmorillonitek10
KI, HZSM-5
5
8
5
10
90
KI, SSA
1

7
8
9
1
1
1
1
KI, SSA
KI, SSA
KI, SSA
KI, SSA
KI, SSA
KI, SSA
KI, SSA
1
88
95
90
87
78
80
0.75
0.75
1.5
2
0
1
2
3
2
2
82
(
continued)

Table 2. Continued
Time
(h)
Yield
(%)
Entry
Substrate
Reagent
Product
14
15
16
17
18
19
KI, SSA
2
80
60
55
85
80
0
KI, SSA
KI, SSA
KI, SSA
KI, SSA
KI, SSA
5
5
1
1.5
5

20
21
22
23
KI, SSA
KI, SSA
KI, SSA
KI, SSA
5
5
5
5
0
0
0
0
a
b
The molar ratio of alcohol/KI/SSA is 1 : 1.2 : 1.2.
Yields refer to pure isolated products and were characterized by comparison of their physical and spectral data (IR, H NMR, MS) with authentic
1
samples.

a
Table 3. KI/SSA used for selective iodination of different alcohols
1
2
3
4
5
a
The progress of the reaction was determined by GC and TLC analysis.

Efficient Method for Iodination of Alcohols
1047
benzylic hydroxyl groups to be iodinated without affecting other OH groups
Table 3, entries 1–3). We also studied the iodination of benzyl alcohol
(
versus 4-methoxybenzyl alcohol and 4-nitrobenzyl alcohol in the presence
of benzyl alcohol. These reactions proceeded with high selectivity in the
presence of KI/SSA, showing the importance of electronic effects upon
these reactions using this technique (Table 3, entries 4, 5).
In conclusion, we have developed a simple, direct, and highly chemo-
selective process for the iodination of benzylic and allylic alcohols using
KI/SSA. The mild reaction conditions, short reaction times, good to high
yields, low cost, and easy preparation and handling of SSA are the advantages
of this method.
EXPERIMENTAL
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 samples and by spec-
1
1
troscopy data (IR, H NMR, and MS analysis). H NMR spectra were
recorded at 300 MHz in CDCl unless otherwise stated, relative to TMS
3
(0.00 ppm). GC analysis was run with a Shimadzu GC-14A.
Preparation of Silica Sulfuric Acid
A 500-mL suction flask was equipped with a constant-pressure dropping
funnel containing chlorosulfonic acid (46.6 g, 0.4 mol) and a gas inlet tube
for conducting HCl gas over an adsorbing solution (i.e., water). The
reaction vessel was charged with 60.0 g of silica gel; the chlorosulfonic acid
was added dropwise over a period of 40 min at rt. The HCl gas was evolved
from the reaction vessel immediately after the addition of few drops of chlor-
osulfonic acid. The mixture was shaken for 30 min at room temperature to
obtain 92.0 g of a white solid powder (SSA).
Iodination of 4-Brombenzyl Alcohol (Typical Procedure)
SSA (1.2 mmol, 0.35 g) was added in several portions to a solution of
4-bromobenzyl alcohol (1 mmol, 0.187 g) and KI (1.2 mmol, 0.2 g) in
CH CN (5 mL). The mixture was stirred at room temperature, and the
3
progress of the reaction was monitored by TLC or GC. After 2 h, the
reaction mixture was diluted with ether (25 mL) and filtered. The organic
layer was washed with an aqueous solution of Na S O (10%, 10 mL), then
2
2 3
H O (2 ꢀ 10 mL). The organic layer was separated and dried over
2
anhydrous Na SO . The solvent was evaporated under reduced pressure,
2
4

1
048
A. R. Hajipour et al.
and the mixture of the products was purified by short column chromatography
(
(
n-hexane–EtOAc, 3 : 1). 4-Bromobenzyl iodide was obtained in 80% yield
1
0.237 g) of crystalline white solid, mp 57–59 8C, H NMR (FT-300 MHz,
CDCl , TMS) d ¼ 7.43 (d, J ¼ 8.5 Hz, 2 H), 7.26 (d, J ¼ 8.5 Hz, 2 H), 4.42
3
2
1
s, 2 H). IR (KBr) cm : 3020, 2900, 2850, 1590, 1490, 1420, 1200, 1150,
(
þ
1
030, 850, 670. MS (EI), m/e (relative intensity): 298 (M þ 2, 3), 296
þ
(
M , 3), 171 (100), 169 (100), 127 (25), 91 (42), 90 (100), 89 (95), 77 (12),
76 (10), 63 (60), 39 (25).
Iodination of 4-Methoxybenzyl Alcohol in the Presence of Benzyl
Alcohol (Typical Procedure)
SSA (1 mmol, 0.28 g) was added in several portions to a mixture of 4-methox-
ybenzyl alcohol (1 mmol, 0.138 g), benzyl alcohol (1 mmol, 0.1 mL), and KI
(
1 mmol, 0.166 g) in CH CN (5 mL). Then the reaction mixture was stirred
3
for 45 min. (The progress of the reaction was followed by TLC/GC.)
-Methylbenzyl iodide was determined in 90% yield, and benzyl alcohol
was intact (Table 3, entry 4).
4
1
IR and H NMR of Some of the Iodinated Products
2
Benzyl iodide: IR (neat) cm : 3010, 2930, 1595, 1485, 1430, 1070, 835, 750,
1
1
6
60. H NMR (FT-300 MHz, CDCl , TMS) d ¼ 7.3–7.0 (m, 5 H), 3.95
3
(
s, 2 H).
2
-Methoxybenzyl iodide: IR (neat) cm : 3015, 2920, 1600, 1480, 1255,
1
4
1
1
200, 1100, 815, 690. H NMR (FT-300 MHz, CDCl , TMS) d ¼ 7.1
3
(
d, J ¼ 7.3 Hz, 2 H), 6.8 (d, J ¼ 7.3 Hz, 2 H), 3.85 (s, 2 H), 3.75 (s, 3 H).
2
-Chlorobenzyl iodide: IR (neat) cm : 3010, 2910, 1595, 1500, 1420, 1400,
1
2
1
210, 1150, 1035, 830, 750, 660. H NMR (FT-300 MHz, CDCl , TMS)
1
3
d ¼ 7.43 (d, J ¼ 9.3 Hz, 1 H), 7.36 (d, J ¼ 9.3 Hz, 1 H), 7.23 (m, 2 H),
4.54 (s, 2 H).
2
-Chlorobenzyl iodide: IR (KBr) cm : 3010, 2915, 1605, 1505, 1490, 1410,
1
4
1
1
205, 1150, 1080, 825, 665. H NMR (FT-300 MHz, CDCl , TMS) d ¼ 7.37
3
(
d, J ¼ 9.5 Hz, 2 H), 7.3 (d, J ¼ 9.5 Hz, 2 H), 4.45 (s, 2 H).
2
-Nitrobenzyl iodide: IR (KBr) cm : 3060, 2980, 1600, 1525, 1400, 1350,
1
4
1
1
220, 1100, 835, 800, 670. H NMR (FT-300 MHz, CDCl , TMS) d ¼ 8.17
3
(
d, J ¼ 8.8 Hz, 2 H), 7.53 (d, J ¼ 8.8 Hz, 2 H), 4.5 (s, 2 H).
2
-Nitrobenzyl iodide: IR (KBr) cm : 3075, 2980, 1595, 1530, 1410, 1345,
1
3
1
1
205, 1160, 1010, 875, 790, 700, 670. H NMR (FT-300 MHz, CDCl , TMS)
3
d ¼ 8.25 (s, 1 H), 8.13 (d, J ¼ 7 Hz, 1 H), 7.72 (d, J ¼ 7.7 Hz, 1 H), 7.51
t, J ¼ 8 Hz, 1 H), 4.51 (s, 2 H).
(

Efficient Method for Iodination of Alcohols
1049
2
Cinnamyl iodide: IR (neat) cm : 3030, 2925, 2850, 1650, 1600, 1495,
1
1
1
450, 1135, 1035, 760, 665. H NMR (FT-300 MHz, CDCl , TMS) d ¼ 7.20
3
(
s, 5 H), 6.75 (d, J ¼ 16.3 Hz, 1 H), 6.55 (m, 1 H), 3.45 (d, J ¼ 6.8, 2 H).
2
-Iodo-1-phenyl ethane: IR (neat) cm : 3125, 2970, 2860, 1600, 1495,
1
1
1
1
445, 1360, 1200, 1025, 965, 845, 760, 675. H NMR (FT-300 MHz,
CDCl , TMS) d ¼ 7.12 (s, 5 H), 4.74 (q, J ¼ 7 Hz, 1 H), 2.46 (d, J ¼ 7 Hz,
3
3
H).
ACKNOWLEDGMENTS
We gratefully acknowledge the funding support received for this project from
the Isfahan University of Technology (IUT), IR Iran (A. R. H.), and grants GM
0
33138, MH 065503, NS 033650 (A. E. R.) from the National Institutes of
Health. Further financial support from Center of Excellency in Chemistry
Research (IUT) is gratefully acknowledged.
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