A practical iodination of aromatic compounds by using iodine and iodic acid

Article abstract of DOI:10.1080/00397910903457332

This article describes simple and efficient method for the iodination of different aromatic amines, hydroxy aromatic aldehydes, hydroxy acetophenones and phenols using iodine and iodic acid in ethanol as a solvent. Notable advantages include mild reaction condition, no need of catalyst, short reaction time, simple practical procedure, giving excellent yield of the product. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903457332

This article was downloaded by: [University of Guelph]
On: 06 July 2012, At: 02:27
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
A Practical Iodination of Aromatic
Compounds by Using Iodine and Iodic
Acid
Avinash T. Shinde a , Sainath B. Zangade b , Shivaji B. Chavan b ,
Archana Y. Vibhute b , Yogesh S. Nalwar b & Yeshwant B. Vibhute b
a P.G. Department of Chemistry, N.E.S. Science College, Nanded,
India
b P.G. Department of Chemistry, Yeshwant Mahavidyalaya, Nanded,
India
Version of record first published: 05 Nov 2010
To cite this article: Avinash T. Shinde, Sainath B. Zangade, Shivaji B. Chavan, Archana Y. Vibhute,
Yogesh S. Nalwar & Yeshwant B. Vibhute (2010): A Practical Iodination of Aromatic Compounds
by Using Iodine and Iodic Acid, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:23, 3506-3513
To link to this article: http://dx.doi.org/10.1080/00397910903457332
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,

demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 40: 3506–3513, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903457332
A PRACTICAL IODINATION OF AROMATIC
COMPOUNDS BY USING IODINE AND IODIC ACID
Avinash T. Shinde,1 Sainath B. Zangade,2 Shivaji B. Chavan,2
Archana Y. Vibhute,2 Yogesh S. Nalwar,2 and
Yeshwant B. Vibhute2
1P.G. Department of Chemistry, N.E.S. Science College, Nanded, India
2P.G. Department of Chemistry, Yeshwant Mahavidyalaya, Nanded, India
This article describes simple and efficient method for the iodination of different aromatic
amines, hydroxy aromatic aldehydes, hydroxy acetophenones and phenols using iodine
and iodic acid in ethanol as a solvent. Notable advantages include mild reaction condition,
no need of catalyst, short reaction time, simple practical procedure, giving excellent yield of
the product.
Keywords: Aromatic compounds; iodination; iodine and iodic acid
INTRODUCTION
The different aromatic compounds have been the subject of numerous studies
due to their organic synthesis as versatile intermediate that can be transformed to
variety of functional groups.[1] Aromatic iodo compounds can be easily functiona-
lized through metal-catalyzed cross-coupling reactions[2] in the synthesis of many
interesting natural products[3] and bioactive material.[4] Iodoaromatic compounds
are used in medicine as drug or diagnostic aids, contractors,[5] and radioactively
labeled markets.[6] They also have important in medicinal and pharmaceutical
research.[7] The chemistry dealing with selective introduction of an iodine atom into
organic molecules thus attracted broad interest in the wider specific community.
Recently direct iodination methods have been intensively developed using iodo-
nium donating system, such as iodine-nitrogen dioxide,[8] iodine F-TEDA-
[1-chloromethyl-4-fluoro-1, 4-diazoniabicyclo [2,2,2] octane-bis-(tetrafluoroborate)],[9]
bis-N-iodosuccinimide,[10] trichloroisocyanuric acid=I2=Wet SiO2,[11] mercury(II)–
oxide-iodine,[12] iodine-monochloride,[13] bis(pyridine)iodonium(I), tetrafluoroborate
CF3SO3H,[14] NIS-CF3SO3H,[15] iodine silver sulfate,[16] iodine-mercury salts,[17]
NaOCl-NaI.[18] However, most of these methods are hazardous or toxic, involve costly
reagents, require high reaction temperatures or demand a long reaction time.
Received August 19, 2009.
Address correspondence to Yeshwant B. Vibhute, Department of Chemistry, VIP Road, Baba
Nagar, Nanded-431602, India. E-mail: drybvibhute@gmail.com
3506

IODINATION OF AROMATIC COMPOUNDS
3507
Scheme 1. Iodination of aromatics.
In our recent communication, iodination of aromatic compounds has been
done using iodine and iodic acid as iodinating agent in solvent ethanol by stirring
method,[19,20] requiring nearly 2 h for complete iodination. Therefore, there is a need
for a method that may be more effective, safer, and faster, giving quantitative yield
of Iodo compound.
We report here in a simple practical procedure of iodination. An advantages of
this method are procedural simplicity, no need of catalyst, clean work up, short
reaction time, and nearly quantitative yield.
To illustrate the advantages of the present method, we have chosen different
reactive hydroxy aromatic aldehydes, hydroxy acetophenones and phenols. Sub-
strate and iodine were dissolved in 95% ethanol, added to it iodic acid dissolved in
minimum amount of water, and refluxed on a water bath for 5 min. on cooling
crystalline product separated out. Iodination occurs at the electron-rich center.
Structures of the compounds were confirmed by taking mixed melting points
with authentic sample or by spectral and elemental analysis (Scheme 1).
EXPERIMENTAL
General Procedure
Melting points were determined in an open capillary tube and are uncorrected.
IR spectra were recorded in KBr on a Perkin-Elmer spectrometer. 1H NMR spectra
were recorded on a Gemini 300-MHz instrument in CDCl3 as solvent and TMS as an
internal standard. Elemental analysis was carried out on a Carlo Erba 1108 analyzer.
The purity of products was checked by thin-layer chromatography (TLC) on
silica-gel.
General Procedures for Iodination of Aromatic Amines, Hydroxy
Aromatic Aldehydes, Hydroxy Acetophenones, and Phenols
Aromatic Compounds (50 mmol), iodine (20 mmol) dissolved in ethanol
(20 ml) by warming, iodic acid (10 mmol) dissolved in water (1 ml) was added with
shaking and refluxed on boiling water bath for 5 min. on cooling solid separated
out. Obtained solid product was filtered and crystallized from ethanol. Purity of
compound was checked by TLC. Physical and analytical data are given in
Tables 1–4.

3508
A. T. SHINDE ET AL.
Table 1. Physical and analytical data of iodo amines
Mp (ꢀC) Found
(Reported)
Sr. No.
1.
Substrate
Product
Yield
75
65 (65)[21]
2.
3.
4.
5.
6.
7.
80
75
81
75
85
80
60 (58)[21]
39 (39–41)[21]
87 (80)[21]
180 (180)[22]
120 (122–123)[21]
122[21]
8.
85
115 (116)[21]
9.
85
75
130 (128–131)[22]
67 (65–70)[22]
10.
11.
60
220 (220–225)[21]

IODINATION OF AROMATIC COMPOUNDS
3509
Table 2. Physical and analytical data of iodo hydroxy aromatic aldehydes
Mp (ꢀC) Found
(Reported)
Sr. No.
Substrate
Product
Yield
82
1.
110 (110)[23]
2.
3.
70
78
172 (172)[23]
182 (180)[24]
4.
5.
6.
85
68
57
76 (78)[23]
80 (81)[23]
135 (136)[24]
7.
75
184 (185)[25]
Spectral Data of Selected Compounds
1
1. 2-Iodo-4-nitroanline: IR (cmÀ1): 3355 (NH); 1611, 1550 (C C) H NMR(CDCl3)
d: 4(s, 2H, NH2), 7.39 (dd, 1H, 3Ar-H). Anal. calcd. for C6H5IN2O2: C, 27.26; H,
1.89; I, 48.10; N, 5.33. Found: C, 27.20; H, 1.81; I 48.23; N, 5.25.
=
2. 2-Iodo-4-chloroaniline: IR (cmÀ1) 3311 (NH); 1604, 1518 (C C) 1H NMR
=
(CDCl3) d: 4 (S, 2H, NH2), 7.42 (S, 1H, 3Ar-H). Anal. calcd. for C6H5IClN:
C, 28.45; H, 1.97; I, 50.19; N, 5.33. Found: C, 28.34; H, 1.88; I, 50.30; N, 5.19.

3510
A. T. SHINDE ET AL.
Table 3. Physical and analytical data of iodo-phenols
Mp (ꢀC) Found
(Reported)
Sr. No.
Substrate
Product
Yield
1.
72
43 (42–44)[22]
2.
3.
4.
78
76
82
100 (105–110)[22]
103 (103)[22]
108–110[22]
5.
6.
84
76
125 (115–119)[22]
120–122[22]
7.
85
90[22]
1
3. 2,6-Dichloro-4-iodoaniline: IR (cmÀ1) 3355 (NH); 1611, 1550 (C C). H NMR
(CDCl3) d: 4.05 (s, 2H, NH2), 7.3 (s, 2H, 3 and 5Ar-H). Anal. calcd. for C6H4 ICl2N:
C, 25.01; H, 1.38; I, 44.09; N, 4.86 Found: C, 25.15; H, 1.43; I, 44.11; N, 4.730.
=
4. 2-Hydroxy-3,5-diiodobenzaldehyde: IR (cmÀ1) 2845 (C-H of CHO), 2719 (C-H of
1
=
=
CHO); 1658 (C O); 1587 (C C); H NMR (CDCl3) d: 8.01 (s, 1H; 6Ar-H), 8.13
(S, 1H; 4Ar-H); 9.97 (s, 1H, CHO), 11.82 (s, 1H, OH). Anal. calcd. for
C7H4I2O2: C, 22.45; H, 1.06; I, 67.91; Found: C, 22.34; H, 1.72; I, 67.83.
5. 2,4-Dihydroxy-3,5-diiodobenzaldehyde: IR (cmÀ1) 2811 (C-H of CHO); 1648
1
=
(C O); 1575 (C-C); H NMR (CDCl3) d: 7.86 (s, 1H, 6ArH), 8.38 (s, 1H, OH),
11.85 (s, 1H, OH), 10.05 (s, 1H, CHO), Anal. Calcd. for C7H4I2O3, C, 21.53; H,
1.02; I, 65.12. Found: C, 21.49; H, 1.12; I, 65.19.
6. 4-Hydroxy-5-iodo-3-methoxybenzaldehyde: IR (cmÀ1) 2827 (C-H of CHO); 2739
1
=
=
(C-H of CHO); 1666 (-C O); 1585 (C C); H NMR (CDCl3) d: 3.98 (s, 3H,
OCH3), 7.34 (s1H, 2Ar-H), 7.58 (s, 1H, 6Ar-H), 8.06 (s, 1H, OH), 9.98 (s, 1H,
CHO). Anal. calcd. for C8H7IO3; C, 34.53; H, 2.51; I, 45.68. Found: C, 34.48;
H, 2.41; I, 45.72.

IODINATION OF AROMATIC COMPOUNDS
3511
Table 4. Physical and analytical data of iodo hydroxy acetophenones
Mp (ꢀC) Found
(Reported)
Sr. No.
1.
Substrate
Product
Yield
84
140 (132)[23]
2.
3.
4.
85
80
85
155
165 162[23]
177 178[23]
5.
6.
7.
82
78
86
89 90[23]
105 104[23]
90[23]
8.
9.
92
90
=
76[23]
156
7. 5-Bromo-2-hydroxy-3-iodoacetophenone: IR (cmÀ1) 1635 (C O); 1580 (C C); H
NMR (CDCl3) d: 6.93 (s, 1H, 4Ar-H), 7.28 (s, 1H, 6Ar-H), 12.85 (s, 1H, OH).
Anal. Calcd. for C8H6BrIO2: C, 28.15; H, 1.75; X, 59.65. Found: C, 28.07; H,
1.62; X, 60.31.
1
=

3512
A. T. SHINDE ET AL.
1
8. 2,4-Dihydroxy-3,5-diiodoacetophenone: IR (cmÀ1) 1640 (C O); 1570 (C-C); H
NMR (CDCl3) d:2.68 (s, 3H, COCH3), 8.68 (s, 1H, 6Ar-H), 8.35 (s, 1H, OH),
11.82 (s, 1H, OH). Anal. Calcd. for: C8H6I2O3: C, 23.76; H, 1.48; X, 62.87. Found:
C, 23.69; H, 1.71; X, 62.89.
=
9. 5-Chloro-2-hydroxy-3-iodo-4-methylacetophenone: IR (cmÀ1) 1645 (C O), 1570
=
1
(C-C). H NMR (CDCl3) d: 2.15 (s, 3H, CH3), 2.68 (s, 3H, COCH3), 8.69 (s,
6H, Ar-H), 11.85 (s, 1H, OH). Anal. Calcd. for C9H8ClIO2: C, 34.83; H, 2.5;
X, 52.33. Found: C, 34.79; H, 2.41; X, 51.94.
ACKNOWLEDGMENTS
The authors are thankful to the Principal, Yeshwant Mahavidyalaya, Nanaed,
for providing laboratory facilities. The authors are also thankful to the director of
Indian Institute of Chemical Technology (IICT), Hyderabad, for providing spectra
of synthesized compounds, and University Grants commission (UGC) Delhi, for
providing major research grant.
REFERENCES
1. Farina, V. In Comprehensive organometallic Chemistry II; E.W. Abel, F.G.A. Stone, and
G. Wilkinson (Eds.); Pergamen Press: Oxford, 1995, vol. 12, pp. 161–240.
2. Diederich, F.; Stang, P. J. Metal Catalysed Cross Coupling Reactions; Wiley-VCH:
Weinheim, Germany, 1988.
3. (a) Larock, R. C.; Lee, N. H. Efficient free radical and palladium catalysed tandem alkene
insertion: a new approach to benzoprostacyclins. J. Org. Chem. 1991, 56, 6253; (b)
Larock, R. C.; Yum, E. K. Synthesis of indoles via palladium catalysed heteroannulation
of internal alkynes. J. Am. Chem. Soc. 1991, 113, 6689; (c) Busacca, C. A.; Johnson, R. E.
Synthesis of novel tetrahydrobenzazepinones. Tetrahedron Lett. 1992, 33, 165; (d)
Swenton, J. S.; Callinan, A.; Wang, S. Efficient synthesis of vinyl ethers of spiroquinol
ketals and their high yield photochemical oxygen to carbon [1, 3]-shift to spiro-fused 2,
5-cycohexadienanes. J. Org. Chem. 1992, 57, 78.
4. (a) Seevers, R. H.; Counsell, R. E. Radioiodination of techniques for small organic
molecules. Chem. Rev. 1982, 82, 574; (b) Nicolaou, K. C. The battle of calicheamicin
g1 1. Angew. Chem., Int. Ed. Engl. 1993, 32, 1377.
5. Sovak, M. Radiocontrast agents; In Handbook of Experimental Pharmacology; Springer:
Berlin, 1993.
6. Seevers, R. H.; Counsell, R. E. Radioiodination of techniques for small organic molecules.
Chem. Rev. 1982, 82, 575.
7. (a) Heindel, N. D.; Burnes, H. D.; Honds, T.; Brandy, L. W., Eds.; Chemistry of Radio-
pharmaceuticals; Masson: New York, 1997; (b) Nicolaou, K. C. The battle of calicheami-
cin g1 1. Angew. Chem., Int. Ed. Engl. 1993, 32, 1377.
8. Noda, Y.; Kashima, M. An efficient and regioselective direct iodination using iodine and
nitrogen dioxide. Tetrahedron Lett. 1997, 38, 6225–6228.
9. Zupan, M.; Iskra, J.; Stavber, S. Mild and regioselective iodination of electron rich
aromatics with N-iodosuccinimide and catalytic trifluoroacetic acid. Tetahedron Lett.
1997, 38, 6305–6306.
10. Carreno, M. C.; Ruano, J. G.; Sanz, G.; Toledo, M. A.; Urbano, A. Mild and regioselec-
tive iodination methoxybenzenes and napthalenes with N-iodosuccinimide. Tetrahedron
Lett. 1996, 37, 4081–4084.

IODINATION OF AROMATIC COMPOUNDS
3513
11. Akhlaghinia, B.; Rahmani, M. Mild and Efficient Iodination of aromatic compounds with
Trichloroisocyanuric Acid=I2=Wet SiO2 System. J. Turk. Chem. 2009, 31,1–6.
12. Orito, K.; Hatakeyama, T.; Takeo, M. Iodination of alkyl aryl ethers by mercury II)
oxide—iodine reagent in dichloroethane. Synthesis 1995, 1273–1277.
13. Hubig, S. M.; Jung, W.; Kochi, J. K. Cation radical as intermediates in aromatic halogen-
ation with iodine monochloride: Solvent and salt effect on the competition between chlori-
nation and iodination. J. Org. Chem. 1994, 59, 6233–6244.
14. Barluenga, J.; Gonzalez, J. M.; Garcia-Martin, M. A.; Campos, P. J.; Asensia, G. Acid
mediated reaction of bis (pyridine) iodonoum (I) tetrafluoroborate witharomatic
compounds: A selective and general iodination method. J. Org. Chem. 1993, 58,
2058–2060.
15. Olah, G. A.; Wang, D.; Sandford, G.; Prakash, G. K. S. Synthetic methods and reagents,
181. Iodination of deactivated aromatics with N-iodosuccinimide in trifluromethanne
sulphonic acid (NIS-CF3SO3H) via in situ generated superelectrophilic iodine (I) triflur-
omethannesulphonate. J. Org. Chem. 1993, 58, 3194–3195.
16. Sy, W. W. Iodination of methoxyamphetamines with iodine and silver sulphate. Tetra-
hedron Lett. 1993, 34, 6223–6224.
17. Bachki, A.; Foubelo, F.; Yus, M. Aromatic iodination with the I2-HgX2 combination.
Tetrahedron 1994, 50, 5139–5146.
18. Edgar, K. J.; Falling, S. N. An efficient and selective method for preparation ofiodophe-
nol. J. Org. Chem. 1990, 55, 5287–5291.
19. Patil, B. R.; Bhusare, S. R.; Pawar, R. P.; Vibhute, Y. B. Iodine and iodic acid: an efficient
reagent for iodination of aryl hyderoxy ketones. Tetrahedron Lett. 2005, 46, 7179–7181.
20. Patil, B. R.; Bhusare, S. R.; Pawar, R. P.; Vibhute, Y. B. Regioselective iodination of
hydroxylated aromatic ketones. Arkivoc 2006, 1, 104–108.
21. Khansole, S. V.; Junne, S. B.; Sayyed, M. A.; Vibhute, Y. B. Convenient and efficient
method for iodination of aromatic amines by pyridinium iodochloride. Synth. Commun.
2008, 38, 1792–1798.
22. Aldrich Chemical Company. Handbook of Fine Chemicals; Aldrich Chemical Company:
Bangalore, India, 2007–2008.
23. Khansole, S.V.; Mokle, S.S.; Sayyed, M.A.; Vibhute, Y.B. PyridiniumIodochloride: An
efficient reagent for iodination of hydroxylated aromatic ketones and aldehydes. J. Chin.
Chem. Soc. 2008, 55, 871–874.
24. Sayyed, M. A.; Junne, S. B.; Vibhute, A. Y.; Vibhute, Y. B. An improved protocol for
synthesis of iodohydroxy benzaldehyde using iodine and iodic acid. Int. J. Chem. Soc.
2008, 6, 192–196.
25. Vibhute, A. Y. Studies on synthesis and biological activity of some new heterocyclic
compounds. Thesis submitted to swami Ramanand Teerth Marathwada University,
Nanded (M.S.), 2008, India.