New halogenation reagent system for one-pot conversion of alcohols into iodides and azides

Article abstract of DOI:10.1081/SCC-100103316

In Situ generation of hydrogen iodide from methanesulphonic acid/sodium iodide in different solvents was found to be an attractive reagent system for the chemoselective conversion of various alcohols to their corresponding iodides. Moreover, treatment of benzylic and allylic alcohols with this reagent system, followed by substitution with azide ion, produced the corresponding azides in one pot in good yields.

Full text of DOI:10.1081/SCC-100103316

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NEW HALOGENATION
REAGENT SYSTEM FOR
ONE-POT CONVERSION OF
ALCOHOLS INTO IODIDES AND
AZIDES*
Ahmed Kamal a , G. Ramesh a & N. Laxman a
a Division of Organic Chemistry, Indian Institute of
Chemical Technology, Hyderabad, 500 007, India
Version of record first published: 09 Nov 2006.
To cite this article: Ahmed Kamal , G. Ramesh & N. Laxman (2001): NEW
HALOGENATION REAGENT SYSTEM FOR ONE-POT CONVERSION OF ALCOHOLS INTO
IODIDES AND AZIDES* , Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 31:6, 827-833
To link to this article: http://dx.doi.org/10.1081/SCC-100103316
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SYNTHETIC COMMUNICATIONS, 31(6), 827–833 (2001)
NEW HALOGENATION REAGENT SYSTEM
FOR ONE-POT CONVERSION OF
ALCOHOLS INTO IODIDES AND AZIDES*
Ahmed Kamal,{ G. Ramesh, and N. Laxman
Division of Organic Chemistry, Indian Institute of
Chemical Technology, Hyderabad 500 007, India
ABSTRACT
In situ generation of hydrogen iodide from methane-
sulphonic acid/sodium iodide in different solvents was found
to be an attractive reagent system for the chemoselective con-
version of various alcohols to their corresponding iodides.
Moreover, treatment of benzylic and allylic alcohols with
this reagent system, followed by substitution with azide ion,
produced the corresponding azides in one pot in good yields.
Alkyl halides, especially iodides, have been useful for the ionic or
radical carbon-carbon coupling reaction. In various synthetic organic reac-
tions, such as substitution, elimination, and rearrangements, they are inter-
mediates of choice. The earlier developed methods for the conversion of
alcohols into iodides have employed phosphorous-based reagents.1–3 These
reagents have now been replaced by triphenylphospine in combination
with a halogen source such as N-iodosuccinamide4 or triiodoimidazole.5–7
* IICT Communication No. 4529.
{ Corresponding author.
827
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

828
KAMAL, RAMESH, AND LAXMAN
All these reactions usually require elevated temperatures and long reaction
times. Recently, trimethylsilyl chloride or boron trifluoride etherate with
sodium iodide has been used for the conversion of allylic alcohols into allylic
iodides.8,9 However, the activation reagents for such procedures are expen-
sive and not very easy to handle. A major difficulty experienced with phos-
phite-based reagent systems is that the triphenylphosphine and its oxides
are difficult to remove from the reaction mixture. They are removed either
by precipitation or chromatography, which is cumbersome and results in
reduced yields. Therefore, this method is particularly inconvenient in large-
scale synthesis. Some of the many existing methods for the conversion of
alcohols to iodides10–12 are generally not selective, therefore a search for
more facile and practical methods that could employ inexpensive reagents
for the chemoselective iodination/azidation is worthwhile.
In our recent studies on the synthesis of some new analogs of natural
products, we were confronted with the challenge of employing a selective
and useful method for the conversion of benzylic/allylic alcohols to their
corresponding iodides without affecting the other susceptible functionalities.
In this endeavour, it was envisaged that organic sulphonic acids and sodium
iodide could offer an immediate source of hydrogen iodide. Herein, we
report methanesulphonic acid-sodium iodide as an efficient reagent system
for the conversion of alcohols to iodides. This reagent system has not been
much explored in organic synthesis except for the reduction of sulphoxides
to the corresponding sulphides.13
In the present work, alkyl, allyl, and benzylic alcohols have been con-
verted to their corresponding iodides in good to excellent yields employing
methanesulphonic acid and sodium iodide reagent system. The iodination
for benzylic, allylic, and tertiary alcohols has been performed by this reagent
system generally employing acetonitrile as the solvent. These conversions
take place with spontaneity (10–20 m) in excellent yields at room tempera-
ture as described14 in Table 1 (1a–1h). Other solvents, such as dichloro-
methane, dichloroethane, and toluene, have also been examined, but no
significant improvement has been observed. Primary and secondary alcohols
(1i–1l) also give the corresponding iodides by employing dichloroethane
as a solvent under reflux conditions. Whereas, it has been observed that
primary and secondary alcohols do not produce their iodo derivatives at

HALOGENATION REAGENT SYSTEM
829
Table 1. Iodination of Alcohols by Methanesulphonic Acid-Sodium Iodide
Reagent System 2a–l
Entry
1a
Productb
Time
Yield (%)
92
15 min
1b
1c
15 min
15 min
90
88
1d
1e
1f
15 min
20 min
20 min
20 min
88
75
80
85
1g
1h
1ia
(C2H5)3C-I
10 min
26 h
89
65
1ja
1ka
1la
CH3(CH2)4CH2I
CH3(CH2)6CH2I
CH3(CH2)9CH2I
8 h
8 h
8 h
71
70
71
aThe reactions for these alcohols have been carried out in dicholormethane at reflux
temperature.
bAll the products have shown satisfactory spectral data.

830
KAMAL, RAMESH, AND LAXMAN
room temperature. The chemoselectivity by this reagent system has been
illustrated in the case of 1d, wherein the benzylic groupalone has been
converted to its iodo form 2d. Therefore, this reagent system could be
used for the selective iodination of benzylic, allylic, and tertiary alcohols
without converting the primary and secondary alcohols at room tempera-
ture. Further, when these reactions were carried out in acetonitrile, the
conversions took longer reaction times (24–48 h).
The present investigation has also been extended towards the azidation
of benzylic and allylic alcohols in acetonitrile with catalytic amount of
aluminium chloride in one pot. It has been observed that the azidation15
of allylic alcohols (1e, f) is very facile and takes place at room temperature.
However, the azidation of benzyl alcohols (1a, b, c, and d) require reflux
conditions. Similar to selective iodination, the azidation in case of 1d takes
place in a selective manner for the benzylic alcoholic group.
In conclusion, we have described an efficient, chemoselective, and
practical procedure for the conversion of various alcohols to their iodides,
which will have wide application in organic synthesis because of its simpli-
city and chemoselectivity. Furthermore, the treatment of allylic and benzylic
alcohols by this reagent system described also offers a convenient method
for the preparation of corresponding azides, which are valuable starting
materials in organic synthesis. The same strategy has a potential for the
preparation of a wide variety of benzylic and allylic compounds. The exten-
sion and further applications of this method are now in progress in our
laboratory.
EXPERIMENTAL
IR spectra were recorded on a IR Nicolet 740 FT IR spectrometer.
1H NMR spectra were recorded on a FT (200 MHz Gemini) spectrometer.
Mass spectra were recorded on either a Micromass 7070h or Finnigan Mat
1020 B mass spectrometer operating at 70 eV. Thin-layer chromotography
was done on precoated silica gel 60f 254 (0.5 mm) glass plates. All the
alcohols were purchased from a local company and used directly as received.

HALOGENATION REAGENT SYSTEM
831
Table 2. Azidation of Benzylic and Allylic Alcohols
Producta
Entry
1a
Yield (%)
65
1b
1c
63
60
1d
58
1e
1f
50
57
aAll the products gave satisfactory spectral data.
All reagents were obtained from commercial suppliers and were used
without further purification.
1
Note: All the compounds are fully characterized by H NMR and IR
spectroscopy and compared with authentic samples.
General Procedure for 2a–h
To a vigorously stirred solution of NaI (596 mg, 4 mmol) and benzyl
alcohol (216 mg, 2 mmol) in acetonitrile (10 mL) under nitrogen is added
methanesulphonic acid (384 mg, 4 mmol) in 2 mL of acetonitrile with a syr-
inge at room temperature. The reaction mixture was allowed to stir for 15 m

832
KAMAL, RAMESH, AND LAXMAN
quenched with water, and extracted with ether (20 mL). The organic layer
was washed with 10% sodium thiosulphate solution and dried over anhy-
drous sodium sulphate. Upon evaporation, crude iodide was obtained. This
was purified by column chromatography on silica gel by eluting with
hexane, giving the benzyl iodide in 92% yield.
General Procedure 3
To a vigorously stirred solution of NaI (596 mg, 4 mmol) and benzyl
alcohol (216 mg, 2 mmol) in acetonitrile (10 mL) under nitrogen was
added methanesulphonic acid (384 mg, 4 mmol) in 2 mL of acetonitrile
with a syringe at room temperature. The reaction mixture was allowed to
stir for 15 m, to which was added anhydrous aluminum chloride (26 mg,
0.2 mmol) and sodium azide (390 mg, 6 mmol), and refluxed for 5 h. The
reaction mixture was then quenched with water and extracted with ether
(20 mL). The organic layer was washed with 10% sodium thiosulphate
solution and dried over anhydrous sodium sulphate. Upon evaporation,
crude azide was obtained. This was purified by column chromatography on
silica gel by eluting with hexane, giving the benzyl azide in 65% yield.
ACKNOWLEDGMENTS
NL is thankful to CSIR (New Delhi) for the award of a Senior
Research Fellowship.
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833
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Received in Japan March 27, 2000