I-/IO3- assemblies as promoters of iodohydrin formation

Article abstract of DOI:10.1080/00397910701239031

The direct conversion of olefins to their corresponding iodohydrins is efficient with I-/IO3- assemblies in an aqueous acidic medium. Iodohydrins were obtained in moderately good yields at ambient reaction conditions without employing any metal catalysts.

Full text of DOI:10.1080/00397910701239031

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I-/IO3 Assemblies as Promoters of Iodohydrin
Formation
Subbarayappa Adimurthy a , Gadde Ramachandraiah a & Pushpito K. Ghosh a
a Central Salt and Marine Chemicals Research Institute , Gijub Badheka
Marg, Bhavnagar, India
Published online: 11 May 2007.
-
To cite this article: Subbarayappa Adimurthy , Gadde Ramachandraiah & Pushpito K. Ghosh (2007) I-/IO3
Assemblies as Promoters of Iodohydrin Formation, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 37:9, 1579-1585, DOI: 10.1080/00397910701239031
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Synthetic Communicationsw, 37: 1579–1585, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701239031
I2/IO23 Assemblies as Promoters of
Iodohydrin Formation
Subbarayappa Adimurthy, Gadde Ramachandraiah, and
Pushpito K. Ghosh
Central Salt and Marine Chemicals Research Institute, Gijub Badheka
Marg, Bhavnagar, India
Abstract: The direct conversion of olefins to their corresponding iodohydrins is efficient
with I2/IO23 assemblies in an aqueous acidic medium. Iodohydrins were obtained in
moderately good yields at ambient reaction conditions without employing any metal
catalysts. The addition of IOH across the olefin follows the Morkovnikov’s rule.
Keywords: iodohydrins, olefins, potassium iodate, potassium iodide
INTRODUCTION
Functionalization of olefins finds applications in various important transform-
ations. The formation of halohydrins from alkenes is a well-established
procedure.[1] Unlike the synthesis of chloro- and bromohydrins in aqueous
media,[2] the preparation of iodohydrins from the reaction of alkenes with
I2/H2O is difficult because of the addition of iodine to the double bond.
Therefore, the iodohydrins are typically obtained by the reaction of
epoxides with hydroiodic acid, elementary iodine.[3] Alternately, the other
reported procedures for the iodohydrin preparation includes the involvement
of redox systems[4] or use of reagents such as N-iodosuccinimide (NIS) in
DME/H2O (DME ¼ 1,2-dimethoxyethane) at 2208C,[5] NIS-H2O in ionic
liquids[6], and I2–H2O in presence of surfactants.[7]
Received September 29, 2006
Address correspondence to Subbarayappa Adimurthy, Central Salt and Marine
Chemicals Research Institute, Gijub Badheka Marg, Bhavnagar 364 002, India.
E-mail: adimurthy@csmcri.org or sadimurthy@yahoo.com
1579

1580
S. Adimurthy, G. Ramachandraiah, and P. K. Ghosh
Finding reaction media to replace polluting organics and metal catalysts is
one of the principles of green chemistry.[8] Water is the cheapest, most
nontoxic and most readily available reaction medium, which makes it an
environmentally and economically attractive solvent. However, the funda-
mental problem of performing reactions in water is that many organic sub-
strates are hydrophobic and sparingly soluble in water. Several approaches
are useful to solubilize the organic substrates in aqueous media; one such
system is carrying out the reactions in the presence of surfactants containing
both polar hydrophobic and polar hydrophilic groups on the same molecules.
Recently Ranu and Banerjee[9] reported the use of ionic liquid [AcMIm]x for
the synthesis of vicinal halohydrins (1.5 equivalent with respect to organic
substrates) by the cleavage of corresponding epoxides at 65 8C. The use of
EPZ-10 catalyst was also employed for obtaining iodohydrins.[10]
RESULTS AND DISCUSSION
Recently we have reported the use of new and environmentally benign
reagents for the halogenation (bromo and iodo) of aromatic compounds
with high atom efficiency.[11] In the course of our study to extend the scope
of the iodide and iodate reagents in organic synthesis, we found that this
reagent facilitates the formation of iodohydrins in a homogeneous system
using dioxane as solvent under ambient conditions. In this article, we report
the apparent formation of hypoiodous acid IOH in situ by treating iodide
and iodate with mineral acids [Eq. (1)] accounts for the formation of iodohy-
drin (Scheme 1).
2Iꢀ þ IO3ꢀ þ 3Hþ ꢀ! 3IOH
ð1Þ
To establish the baseline reactivity of hypoiodous acid IOH with different
olefins in an aqueous acidic medium, the initial study was carried out using
cyclohexene in different solvent media, and the results are summarized in
Table 1.
The iodohydroxylation of cyclohexene with IOH is shown in Scheme 1.
The reaction probably proceeds through the stepwise formation of iodonium
cation intermediate (in situ formation of Iþ OH2) followed by the regioselec-
tive nucleophilic attack of OH2 leading to the formation 2-iodocyclohexanol.
When a molar equivalent of olefin was employed with respect to the reagent
Scheme 1.

I2/IO23 Assemblies as Promoters of Iodohydrin Formation
1581
Table 1. Optimization of reaction conditions for iodohydrin formation with cyclo-
hexene at rt
Entry
Substrate equivalent
Solvent
Yield (%)a
Iodohydrin/diiodide
1
2
3
4
5
6
1.0
1.2
1.5
1.0
1.2
1.5
CH2Cl2
CH2Cl2
CH2Cl2
Dioxane
Dioxane
Dioxane
65
66
66
69
69
72
75/25
75/25
82/18
89.5/10.5
92/08
100/0
aIsolated yields with respect to the reagent.
(IOH), the formation of diiodo derivative was observed. In dichloromethane
solvent medium, even with 1.5 equivalent of olefin, the yields almost
remain but the diiodo derivative decreased (Table 1, entry 3), whereas in
1,4-dioxane medium with increasing the olefin equivalents, the diiodo deriva-
tive formation is suppressed and total yields increased (Table 1, entries 4 to 6).
The present method is based on this concept, where a mixture of 0.66 mol
equiv. of potassium iodide and 0.33 mol equiv. of potassium iodate is
treated with 1 mol equiv. of a mineral acid, resulting in the in situ
formation of hypoiodous acid (IOH) [Eq. (1)], which can effect the iodo
hydroxy addition across olefins (Scheme 1).
The results obtained with some representative alkenes for the iodohydrox-
ylation at room temperature are summarized in Table 2. It was found that the
treatment of cyclohexene (1.5 equivalent) with IOH generated in situ during
the course of the reaction produced only 2-iodocyclohexanol in good yield.
Styrene and 4-methyl styrene gave 90 and 72% total yield with 83% and
80.5% selectivity of iodohydrin, respectively, when 1.5 mol equiv. of
substrate were employed, whereas cyclooctene gave more than 96% of iodo-
hydrin derivative with traces of diiodo derivative even when 1 mol equiv. of
the substrates was used (Table 2, entry 2).
In contrast to the iodohydroxylation of cyclohexene (Scheme 2), the
1-octene afforded about a 4:1 regioisomeric mixture of 1-iodo-2-octanol
and 2-iodo-1-octanol (Scheme 2). The nucleophilic addition of hydroxide
ion to the iodonium ion intermediate at more hydrogen-enriched carbon
atom gave Morkovnikov (route 1) and anti-Morkovnikov (route 2) products
in dioxane medium. A similar strategy was observed in the case of
1-hexene, resulting in regioisomers 1-iodo-2-hexanol and 2-iodo-1-hexanol
in 9:1. In straight chain alkenes, the major Morkovnikov product formation
was observed, which is in accordance with the properties of nucleophilic
addition reactions across the unsymmetrical C-C double bonds.
In summary, this procedure serves as a novel and potential method for the
synthesis of iodohydrins in moderate to good yields in aqueous medium. I2/
IO23 assemblies generate a reactive species, IOH, in situ upon addition of

1582
S. Adimurthy, G. Ramachandraiah, and P. K. Ghosh
Table 2. Synthesis of iodohydrins from olefins
Product
Time Total yield
(%)a
Entry
1
Substrate
(h)
Major
Minor
—
1.0
72
2
3
1.0
2.0
28b
90
4
1.5
72
5
6
1.0
1.5
55
40
c
d
aIsolated yields obtained after column chromatography.
bYield based on the recovery of starting material.
cRegioisomers obtained in 4:1 ratio.
dRegioisomers obtained in 9:1 ratio; all the reactions carried out at room temperature
using dioxane as solvent.
Scheme 2. Iodohydroxylation of 1-octene.

I2/IO23 Assemblies as Promoters of Iodohydrin Formation
1583
mineral acids to promote iodohydrin constitution. The workup procedure is
simple and convenient, and the reaction rates are comparatively faster.
Reactions were carried out at ambient conditions without the use of any
metal catalysts. The advantage of the present procedure is the broad avail-
ability of the reagents.
EXPERIMENTAL
Analytical-grade substrates were purchased from Aldrich Chemicals and used
without further purification. Proton NMR spectra were recorded on a Bruker
200-MHz, (13C NMR 50 MHz) FT-NMR DPX 200 in CDCl3 with tetra-
methylsilane (TMS) as an internal standard. Microanalyses were performed
on a Perkin-Elmer 4100 elemental analyzer, and IR spectra were recorded
on Perkin Elmer GX 2000 spectrometer. Compounds were purified by
column chromatography over silica gel (100–200 mesh from SD Fine
Chemicals) using hexane and ethyl acetate as eluents.
Procedure for the Synthesis of 2-Iodocyclohexanol
A solution of cyclohexene (1.50 g, 18.3 mmol), potassium iodide (1.35 g,
8.132 mmol), and potassium iodate (0.87 g, 4.065 mmol) was prepared in
dioxane (10 mL) and water (30 mL). This mixture was treated at room temp-
erature with dilute sulphuric acid (12.19 mmol) for 60 min, stirred for an
additional 30 min, and extracted with diethylether (25 mL ꢁ 3). The
combined organic extract was washed with dilute sodium thiosulphate (5%),
water, and brine and dried over anhydrous sodium sulphate. Evaporation of
ether left the crude product, which was purified by column chromatography
over silica gel (hexane–ethyl acetate 9:1) to get the pure 2-iodocyclohexanol
as a colorless liquid (1.984 g, 8.779 mmol) in 72% yield whose spectroscopic
data (1H NMR, 13C NMR, and IR) are in good agreement with those of
authentic samples.[3,4,7] All the known products’ spectroscopic data are
compared with the authentic samples except for three new compounds
(entry 2 and 4 from table 2).
Data
1
2-Iodocyclooctanol: H NMR (CDCl3-TMS): (d) 1.50–1.80 (8H, m), 2.15–
2.22 (3H, m, J ¼ 5.4), 2.39–2.54 (1H, m), 2.73 (1H, br s), 3.84–3.92 (1H,
m), 4.47–4.58 (1H, m, J ¼ 4). 13C NMR (CDCl3—50 MHz): (d) 22.31,
27.12, 33.77, 35.03, 35.18, 37.03, 37.56, 71.73. IR, nmax (neat): 3420, 2933,
2860, 2251, 2141, 1646, 1472, 1447, 1366, 1231, 1064, 1039, 983, 909,
732, 649 cm21
.

1584
S. Adimurthy, G. Ramachandraiah, and P. K. Ghosh
1
2-Iodo-1-[4-methylphenyl] ethanol: H NMR (CDCl3-TMS): (d) 2.31 (3H,
s), 2.67 (1H, br s), 3.32–3.38 (2H, t, J ¼ 4.4), 4.69–4.75 (1H, q, J ¼ 4.4),
7.09–7.23 (4H, m, J ¼ 7.2). 13C NMR (CDCl3—50 MHz): (d) 15.74,
21.74, 74.40, 126.24, 128.00, 129.84, 138.56. IR, nmax (neat): 3450, 3059,
1651, 1562, 1477, 1437, 1231, 1146, 1022, 1069, 833, 779, 758, 691 cm21
.
CONCLUSION
In summary, this procedure serves as a novel and potential method for the
synthesis of iodohydrins moderate to good yields in aqueous medium. I2/
IO23 assemblies generate a reactive species, IOH, in situ upon the addition
of mineral acids to promote iodohydrin constitution. The workup procedure
is simple and convenient, and the reaction rates are comparatively faster.
Reactions were carried out at ambient conditions without the use of any
metal catalysts. The advantage of the present procedure is the broad avail-
ability of the reagents.
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