Pyridinium lodochloride: An efficient reagent for lodination of hydroxylated aromatic ketones and aldehydes

Article abstract of DOI:10.1002/jccs.200800130

Direct iodination of several reactive aromatic compounds like hydroxy substituted acetophenones and aldehydes with pyridinium iodochloride (PyICl) proceeded smoothly to afford the corresponding aromatic iodides in good to excellent yield. Pyridinium iodochloride has been found to be an efficient solid iodinating reagent with no hazardous effect and it can be handled safely.

Full text of DOI:10.1002/jccs.200800130

Journal of the Chinese Chemical Society, 2008, 55, 871-874
871
Pyridinium Iodochloride: An Efficient Reagent for Iodination of
Hydroxylated Aromatic Ketones and Aldehydes
Sandeep V. Khansole, Shyam S. Mokle, Mudassar A. Sayyed and Yeshwant B. Vibhute*
P.G. Department of Chemistry, Yeshwant Mahavidyalaya, Nanded 431 602, (MS) India
Direct iodination of several reactive aromatic compounds like hydroxy substituted acetophenones
and aldehydes with pyridinium iodochloride (PyICl) proceeded smoothly to afford the corresponding aro-
matic iodides in good to excellent yield. Pyridinium iodochloride has been found to be an efficient solid
iodinating reagent with no hazardous effect and it can be handled safely.
Keywords: Iodination; Aromatic acetophenones; Aromatic aldehydes; Pyridinium iodochloride.
INTRODUCTION
The iodination of aromatic carbonyl compounds has
nium tetrafluoroborate (IPy2BF4),18 but in these reactions
HBF4 as the acid is required to liberate the iodinating agent
and neutralize pyridine; to improve the yield of product
slightly an excess amount of reagent was required. Re-
cently in our previous communication, iodination of aro-
matic compounds was demonstrated using iodine and iodic
acid as an iodinating agent.19,20
been the subject of numerous studies due to the potential of
the products to serve as intermediates in organic synthesis
and to act as bacterial and fungicidal agents.1 Aromatic io-
dides have long been used in organic synthesis as versatile
intermediates that can be transformed into a variety of func-
tional groups.2 They can be easily functionalized through
metal catalyzed cross coupling reactions3 in the synthesis
of many interesting natural products4 and bioactive materi-
als.5 Iodoaromatic compounds are used in medicine as drug
or diagnostic aids, contrastors6 and radioactively labeled
markers. They also have importance in medicinal and phar-
maceutical research.7 The chemistry dealing with selective
introduction of an iodine atom into an organic molecule has
thus attracted broad interest in the wider scientific commu-
nity.
Due to the poor electrophilic strength of iodine, direct
iodination of aromatic rings with iodine is difficult and re-
quires the presence of an activating agent in order to pro-
duce a strongly electrophilic I+ species. However some of
the existing methods have associated environmental haz-
ards with respect to handling and storage of molecular io-
dine, strongly acidic conditions, expensive and complex
catalyst, toxic metallic compounds and rare oxidizing re-
agents that are difficult to prepare. Therefore there is a need
for a simple, less expensive and safer method for iodination
of hydroxy aromatic acetophenones and aldehydes. We re-
port here iodination of several aromatic hydroxy aceto-
phenones and aldehydes by using pyridinium iodochloride
as iodinating agent.
Iodohydroxy aromatic ketones can be prepared by
Fries rearrangement8 of iodinated phenyl aromatic esters;
however, after the Fries rearrangement, steam distillation is
required to separate the isomer which is a time consuming
method and iodophenols are not easily available.
In recent years, direct iodination methods have been
intensively developed using iodinium donating systems,
such as iodine-tetrabutylammonium peroxydisulfate,9 BuLi-
CF3CH2I,10 iodine-nitrogen dioxide,11 iodine-F-TEDA-
BF4,12 iodine-iodine pentoxide,13 iodine monochloride,14
NIS-CF3SO3H,15 iodine-mercury salts,16 and NaOCl-NaI.17
The iodination of some unsaturated compounds in the
presence of HBF4 was reported using bis(pyridine) iodo-
RESULTS AND DISCUSSION
To illustrate the action of the proposed reagent we se-
lected several reactive aromatic substrates like hydroxy
substituted acetophenones and aldehydes (Scheme I). The
reaction was carried out by heating hydroxy ketones or al-
dehydes with pyridinium iodochloride on a water bath for 1
h using methanol as solvent (Table 1).
The isolated product indicated a regioselective iodin-
* Corresponding author. Tel: +91-2462-236835; Fax: +91-2462-253726; E-mail: svkhansole@yahoo.co.in

872 J. Chin. Chem. Soc., Vol. 55, No. 4, 2008
Khansole et al.
mass spectra were recorded on a Jeol D-300 spectrometer
at 70 eV. The halogen (iodine) analysis was carried out in
laboratory by the Parr bomb method.
Scheme I
Preparation of pyridinium iodochloride
To a solution of pyridine (7.9 g, 0.1 mole) in acetic
acid, a solution of iodine monochloride (16 g, 0.1 mole) in
acetic acid was added slowly at 0 °C with continuous stir-
ring. The pale yellow solid obtained was filtered, dried and
recrystallised by ethyl alcohol. The purity of reagent was
checked by thin layer chromatography.
ation had occured at the electron rich ortho or para posi-
tion. When the ortho position was blocked, iodination only
took place at the para position. Only nuclear iodination oc-
curs and not at the side chain that is at –CH3 or –COCH3.
Typical procedure for iodination of hydroxylated aro-
matic ketones and aldehydes by pyridinium iodochlo-
ride
5-Bromo-2-hydroxy acetophenone (0.22 g, 1 mmol)
and pyridinium iodochloride (0.24 g, 1 mmol) were dis-
solved in methanol (15 mL) and refluxed on a water bath
for 2 h. The content was poured in ice cold water; the solid
that gets separated was filtered and recrystallised from
ethyl alcohol. By using two equivalents of pyridinium iodo-
chloride and one equivalent of substrate, diiodinated prod-
ucts were obtained.
CONCLUSION
In summary, a simple and convenient method for the
iodination of hydroxylated aromatic acetophenones and al-
dehydes has been developed. The advantages include no
catalyst, mild conditions, simple operation and short reac-
tion time with excellent yield. Since the reagent is solid it
can be easily weighed and has no hazardous effect.
SELECTED SPECTROSCOPIC DATA
EXPERIMENTAL SECTION
General procedures
5-Bromo-2-hydroxy-3-iodoacetophenone
Melting points were determined in an open capillary
tube and are uncorrected. The purity of the compound has
been checked by TLC. IR spectra were recorded in KBr on
a Perkin Elmer spectrometer. 1H NMR and 13C NMR spec-
tra were recorded in CDCl3 on a Varian Gemini 200 NMR
spectrometer using TMS as an internal standard. Elemental
analysis was carried out on a Carlo Erba 1108 analyzer. The
IR (cm-1) umax: 1635 (C=O), 1580 (C=C). H NMR
1
(CDCl3) d: 2.7 (s, 3H, COCH3), 7.82 (s, 1H, 4 Ar-H), 8.2 (s,
1H, 6 Ar-H), 12.85 (s, 1H, OH). 13C NMR (CDCl3) d: 24.2,
87.6, 115.2, 129.4, 131.2, 144.5, 167.3, 199.5; MS m/z
(M+) 340; Anal. calcd for C8H6BrIO2: C, 28.15; H, 1.75; X,
59.65. Found: C, 28.07; H, 1.62; X, 60.31.
Table 1. Iodination of hydroxylated aromatic acetophenones and aldehydes by pyridinium iodochloride
M.P. °C
Entry
Substrate
Product
Yield (%)
Found
Lit.
1
2-Hydroxyacetophenone
2-Hydroxy-3,5-diiodoacetophenone
4-Hydroxy-3,5-diiodoacetophenone
5-Bromo-2-hydroxy-3-iodoacetophenone
5-Chloro-2-hydroxy-3-iodoacetophenone
2,4-Dihydroxy-3,5-diiodoacetophenone
84
80
85
89
82
80
85
82
86
79
87
83
132
160
104
90
13221
16222
10521
8921
17823
7621
2
4-Hydroxyaetophenone
3
5-Bromo-2-hydroxyacetophenone
5-Chloro-2-hydroxyacetophenone
2,4-Dihydroxyacetophenone
4
5
177
79
6
5-Chloro-2-hydroxy-4-methylacetophenone 5-Chloro-2-hydroxy-3-iodo-4-methylacetophenone
7
4-Hydroxy-3-methoxybenzaldehyde
2-Hydroxybenzaldehyde
4-Hydroxy-5-iodo-3-methoxybenzaldehyde
2-Hydroxy-3,5-diiodobenzaldehyde
184
111
194
77
18524
11025
19526
7827
8
9
4-Hydroxybenzaldehyde
4-Hydroxy-3,5-diiodobenzaldehyde
10
11
12
5-Chloro-2-hydroxybenzaldehyde
5-Bromo-2-hydroxybenzaldehyde
2,4-Dihydroxybenzaldehyde
5-Chloro-2-hydroxy-3-iodobenzaldehyde
5-Bromo-2-hydroxy-3-iodobenzaldehyde
2,4-Dihydroxy-3,5-diiodobenzaldehyde
80
8127
173
---

Iodination of Aromatic Ketones and Aldehydes
J. Chin. Chem. Soc., Vol. 55, No. 4, 2008 873
5-Chloro-2-hydroxy-3-iodoacetophenone
11.85 (s, 1H, OH). 13C NMR (CDCl3) d: 74.8, 81.1, 120.2,
141.3, 168.9, 184.4, 192.3; MS m/z (M+) 390; Anal. calcd
for C7H4I2O3, C, 21.53; H, 1.02; I, 65.12. Found: C, 21.49;
H, 1.12; I, 65.19.
IR (cm-1) umax: 1630 (C=O), 1570 (C=C). H NMR
(CDCl3) d: 2.75 (s, 3H, COCH3), 7.60 (s, 1H, 4 Ar-H), 7.83
(s, 1H, 6 Ar-H), 12.85 (s, 1H, OH). 13C NMR (CDCl3) d:
23.4, 86.7, 128.1, 129.1, 144.4, 164.4, 197. MS m/z (M+)
296.5; Anal. calcd for C8H6ClIO2: C, 32.37; H, 2.02; X,
54.80. Found: C, 32.31; H, 2.11; X, 54.62.
1
ACKNOWLEDGEMENTS
The authors are thankful to the principal Yeshwant
Mahavidyalaya, Nanded, for providing laboratory facili-
ties. The authors are also thankful to the Director of IICT,
Hyderabad, for providing spectral data and UGC New
Delhi, for providing research grant.
2-4-Dihydroxy-3,5-diiodoacetophenone
IR (cm-1) umax: 1640 (C=O), 1610 (C=C). H NMR
1
(CDCl3) d: 2.68 (s, 3H, COCH3), 8.68 (s 1H, 6 Ar-H), 8.35
(s, 1H, OH), 11.82 (s, 1H, OH). 13C NMR (CDCl3) d: 23.9,
73.6, 79.7, 121.9, 167, 182, 197.5; MS m/z (M+) 404; Anal.
calcd for C8H6I2O3: C, 23.76; H, 1.48; X, 62.87. Found: C,
23.69; H, 1.71; X, 62.89.
Received December 13, 2007.
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