A useful and convenient synthetic protocol for iodination of organic substrates using a combination of vanadyl acetylacetonate, hydrogen peroxide, and sodium iodide

Article abstract of DOI:10.1246/bcsj.20120155

A wide variety of organic substrates can be iodinated selectively in good yields by employing a combination of vanadyl acetylacetonate, hydrogen peroxide, and sodium iodide at ice-bath temperature. Good yield, selectivity, use of cost effective reagents, and mild and environmentally benign reaction conditions are some of the major advantages of this protocol.

Full text of DOI:10.1246/bcsj.20120155

© 2012 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 85, No. 11, 1239-1243 (2012) 1239
A Useful and Convenient Synthetic Protocol for Iodination of
Organic Substrates Using a Combination of Vanadyl Acetylacetonate,
Hydrogen Peroxide, and Sodium Iodide
Abu T. Khan* and Shahzad Ali
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India
Received May 31, 2012; E-mail: atk@iitg.ernet.in
A wide variety of organic substrates can be iodinated selectively in good yields by employing a combination of
vanadyl acetylacetonate, hydrogen peroxide, and sodium iodide at ice-bath temperature. Good yield, selectivity, use
of cost effective reagents, and mild and environmentally benign reaction conditions are some of the major advantages of
this protocol.
Organohalogen compounds are distributed in nature1 and
[VO(acac)2]/H2O2/NaI
Organic substrates
Iodinated product
serve as useful synthetic precursors for Sonogashira and Suzuki
coupling reactions2 as well as for preparation of organolithium,
Grignard reagents,3 and Wittig reagents,4 which are extensively
used in C-C bond forming reactions. Due to poor the
electrophilicity of molecular iodine, it cannot be used alone
for iodination reaction. Iodinated compounds are extensively
also used for C-N and C-S cross-coupling reaction5 and in
medical diagnosis as radioactivity labeled markers.6
Taking cues from the discovery of vanadium bromoper-
oxidase (VBrPO),7,8 a vanadium enzyme which catalyzes the
oxidation of bromide by hydrogen peroxide, we have developed
numerous synthetic methodologies such as cleavage of di-
thioacetals and oxathioacetals, hydrolysis of 1-thioglycosides,
synthesis of bromoflavones and ¡-monobrominated 1,3-dicar-
bonyl compounds using a combination of V2O5/H2O2/NH4Br.9
Biomimicking studies of iodoperoxidases like bromoperoxi-
dases10-12 have not yet been investigated by employing a
vanadium complex. Therefore, vanadyl acetylacetonate was
chosen as it can form selectively vanadium(V) monoperoxo
complex, which may change the course of the reaction pathway.
Though numerous reagents have been developed for iodination
reaction of organic substrates over the years,13 still there is a
further scope to develop a new methodology, which might work
under mild reaction conditions.
The usefulness of vanadyl acetylacetonate was demonstrated
by West et al. recently for the olefination of ¡,¡¤-divinyl
ketones through catalytic Meyer-Schuster rearrangement14a
and synthesis of benzimidazoles.14b It was well known in the
literature that it can also be used for asymmetric oxidation of
sulfides15a and oxidation of cyclohexane into cyclohexanol,15b
epoxidation of allylic alcohols15c in the presence of either
hydrogen peroxide or tert-butylhydroperoxide (TBHP) as well
as conversion of bis-homoallylic alcohols into functionalized
cis-THFs by catalytic olefin epoxidation followed by epoxide
ring opening,15d and cleavage of dithioacetals of sugars into
aldehyde sugars.15e
EtOAc, 0-5 °C
1
2
Scheme 1. Iodination of organic substrates.
Literature survey reveals that the following reagents have
been used for ¡-iodination of 1,3-dicarbonyl compounds such
as periodic acid in glacial acetic acid,16 iodine in presence
of cooxidants,17 NIS with other additive,18 Koser’s reagent
(HTIB) along with MgI2,19 and KI/NaNO2/O2/H2SO4.20 Most
of the above methods have some demerits such as they are not
applicable for a wide range of substrates, provide low yield
and poor selectivity,16 high cost of the reagents18 and longer
reaction time.20 In fact, it is difficult to obtain selectively
¡-iodinated 1,3-dicarbonyl compounds. In this paper, we would
like to report the iodination of various organic substrates using a
combination of [VO(acac)2]/H2O2/NaI as shown in Scheme 1.
Results and Discussion
In this study, the catalyst vanadyl acetylacetonate was pre-
pared according to a literature procedure.21 To find suitable
reaction conditions, benzoyl acetone (1a) was chosen as a model
substrate for optimization of the reaction conditions. Several
reactions were examined using different amounts of [VO-
(acac)2] and NaI. The best yield of iodinated product 2a was
obtained using the combination of substrate:[VO(acac)2]:H2O2:
NaI (1.0:0.2:4.4:2.0 equiv), respectively (Table 1, Entry 5).
After screening of various solvent systems such as CH2Cl2,
CH3CN, CH3OH, and CH3COCH3 (Table 1, Entries 7-10), it
was noted that ethyl acetate was the best solvent for obtaining
mono-iodinated product in terms of yield and reaction time. To
compare the effectiveness of [VO(acac)2] as compared to other
vanadium compounds, we have conducted the reaction with
V2O5 and NH4VO3 as well as without [VO(acac)2], respectively
and the results are summarized in Table 1 (Entries 11-13). In
the absence of [VO(acac)2] only trace quantities (<5%) of the
desired mono iodinated product 2a was produced and unreacted
starting material was recovered in high yield. From these
observations, it is quite clear that vanadyl acetylacetonate
Our present aim is to investigate whether selective iodination
can be achieved using in situ generated iodonium ion or not.
Published on the web October 27, 2012; doi:10.1246/bcsj.20120155

1240 Bull. Chem. Soc. Jpn. Vol. 85, No. 11 (2012)
Synthetic Protocol for Iodination of Organic Substrates
Table 1. Optimization of the Reaction Conditions for the Selective ¡-Iodination of Benzoyl Acetonea)
Entry
Catalyst used
mol %
NaI/equiv
Solvent
Time/min
Yieldb)/%
1
2
3
4
5
6
7
8
9
10
11
12
13
[VO(acac)2]
[VO(acac)2]
[VO(acac)2]
[VO(acac)2]
[VO(acac)2]
[VO(acac)2]
[VO(acac)2]
[VO(acac)2]
[VO(acac)2]
[VO(acac)2]
V2O5
10
15
20
20
20
20
20
20
20
20
20
20
00
2.0
2.0
1.5
1.7
2.0
2.2
2.0
2.0
2.0
2.0
2.0
2.0
2.0
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
CH2Cl2
CH3CN
CH3OH
CH3COCH3
EtOAc
EtOAc
EtOAc
30
25
25
25
25
25
25
25
10
35
25
15
35
59
75
73
81
91
90
66
69
65
72
38
20
05
NH4VO3
Without [VO(acac)2]
a) All the reactions were carried out with 1 mmol of benzoyl acetone. b) Isolated yield.
OCH3
OCH3
OCH3
OCH3
I
VO(acac)2/H2O2/NaI
H3CO
OH
H3CO
OH
EtOAc, 0-5 °C
12 h, 60 %
OCH3O
1r
OCH3O
2r
Scheme 2.
plays a crucial role for the formation of product. To prove the
usefulness of the present protocol, similar reactions were carried
out with molecular iodine (1 equiv) and hydrogen peroxide (4.4
equiv) in ethyl acetate as well as with molecular iodine (1 equiv)
and [VO(acac)2] (0.2 equiv) under identical conditions. We have
obtained 56% and 38% yield respectively based on starting
material recovery. From these results we may conclude that
a combination of [VO(acac)2], NaI and H2O2 is essential for
effective conversion of the starting material into products. The
aniline, N-methylaniline, 4-ethylaniline, and phenol were also
examined under similar reaction conditions. We have obtained
only monoiodinated products 2l-2n regioselectively in good
yields as shown in Table 2. It was observed that 10 mol %
[VO(acac)2] is required for complete conversion of aniline into
4-iodoaniline in 90% yield when the reaction was carried out
with 10 mmol scale. From this observation, we may conclude
iodination can be performed with lesser amounts of [VO-
(acac)2]. Unfortunately, we obtained a mixture of products in
the case of phenol under similar reaction conditions.
1
product 2a was characterized by recording H and 13C NMR
spectra and elemental analysis. Next, dibenzoylmethane (1b)
was subjected to iodination under similar reaction conditions
and the product 2b was isolated in 90% yield.
To extend the scope and general applicability of this
protocol, pyrazole derivatives 1p and 1q were also iodinated
easily and provided the desired products 2p and 2q, respec-
tively in very good yields as shown in the Table 2.
These successful results further motivated us to investigate
the iodination reaction with cyclic 1,3-diketones such as
dimedone (1c) and 1,3-cyclohexanedione (1d) using the same
combination under identical reaction conditions. The iodinated
products 2c and 2d were obtained in fairly good yields.
To examine the efficacy of the present protocol, various ¢-
esters 1e-1k were subjected to iodination reactions with the
same combination by following the same experimental proce-
dure. The mono ¡-iodinated ¢-ketoesters 2e-2k were obtained
in good yields (Entries 5-11), which is shown in Table 2.
Very recently, many new reagents have been developed by
To verify competitive iodination reaction between aromatic
rings and electron-deficient double bonds, we have carried out
an iodination reaction with (E)-1-(2-hydroxy-4,6-dimethoxy-
phenyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one (1r) under
similar reaction conditions, which are shown in Scheme 2.
From the observation, it reveals iodination at the aromatic ring
is preferred over conjugated double bonds.
1
All these products were characterized by recording H and
13C NMR spectra and elemental analysis. Compounds 2a,17c
2b,20 2c,17c 2e,17c 2f,20 2h,20 2j,18a 2k,18a 2l,25 2m,25 2p,28b and
2q28b have previously been reported and NMR data are in good
agreement with the literature data.
various groups for aromatic iodination such as 18-crown-
¹ 22
6-supported ICl2
,
NIS/In(OTf)3,23 ICl/In(OTf)3,24 I2/
H5IO6,25 TMADCI,26 and benzyltriethylammonium dichloro-
iodate/NaHCO3.27 The only demerits of these reagents are they
have to be prepared prior to use and are expensive.
We put forward a proposed mechanism that the interaction of
vanadyl acetylacetonate with hydrogen peroxide can generate
mono peroxo complex of vanadium(V) (Scheme 3),15b which
can oxidize iodide ion to iodonium ion, which may exist in
To verify further the scope of the present protocol, the
iodination reactions of electron-rich aromatic substrates such as
¹
solution as HOI or I2 or I3 . Then in situ generated iodonium

A. T. Khan et al.
Bull. Chem. Soc. Jpn. Vol. 85, No. 11 (2012) 1241
NaI Time Yielda)
Table 2. Iodination of Various Organic Compounds Using
[VO(acac)2]/H2O2/NaIa)
Continued:
Entry Substrate (a)
Products (b)
NaI Time Yielda)
/equiv /h
/%
Entry Substrate (a)
Products (b)
/equiv /h
/%
OH
Mixture of
products
O
O
O
O
O
O
15
2.0
2.0
1.0
1.0
®
1
2
2.0
2.0
0.5
91
Ph
Ph
Ph
Ph
1o
H
O
I
1a
1b
2a
2b
I
O
N
N
N
16
90
92
3.5
90
67
Ph
Ph
N
H
I
H
H
1p
2p
I
in-
stant
N
N
17
2.0
6.5
3
2.0
O
O
O
OH
OH
O
N
H
N
Ph
Ph
H
1q
2q
1c
2c
I
a) The reactions were performed with 1 mmol of substrates.
b) Isolated yield.
in-
stant
4
5
6
7
2.0
2.0
2.5
2.0
62
87
92
73
O
O
1d
1e
1f
2d
I
O
O
O
O
O
O
O
O
O
VIV
O
O
O
11.5
24
1
OtBu
OtBu
H
O
I
O
H
H2O2
2e
2f
O O
H
O
H
B
O
O
O
O
O
VIV
Ph
OEt
OEt
Ph
OEt
OEt
O
O
O
VIV
H
O
I
O
O
O
O O
A
H
C
H2O
I
1g
2g
H
O
O
O
O
OH
O
VIV
O
OH
I
O
VIV
HO
O
O
O
O
O
8
9
2.0
2.5
2.0
1
26
16
90
80
75
OEt
OEt
I
1h
2h
O
O
O
O
O
O
D
O
E
I
(HOI ≡ I2 ≡ I3
)
EtO
OEt EtO
OEt
OEt
H
O
I
1i
2i
O
O
OEt
10
I
Iodinated product
Organic substrate
1j
2j
Ph
Ph
Scheme 3. Probable mechanism for the formation of iodi-
O
O
O
O
nated product.
11
12
2.0
2.0
13
79
85
OEt
OEt
I
1k
2k
ion was successfully trapped by the organic substrates to afford
iodinated compounds. The cycle continues by further regener-
ation of the peroxo complex by the action of the intermediate
with H2O2. However, the correct oxidized species is not known
yet, which we are trying to determine.
NH2
NH2
8.0
1l
2l
I
NHCH3
NHCH3
Conclusion
13
14
2.0
2.0
8.0
8.0
87
84
In conclusion, we have demonstrated an important and
efficient method for the mono-iodination of 1,3-dicarbonyl
compounds, anilines and pyrazoles by using a combination of
[VO(acac)2]/H2O2/NaI in ethyl acetate. It was observed that
most of the halogenation reactions are carried out in halo-
genated solvents such as dichloromethane, chloroform, and
carbon tetrachloride, which is replaceable with non-halogented
less expensive solvent such as ethyl acetate. In addition, the
reaction can be done in the presence of lower amounts of
[VO(acac)2] if the reaction is performed in large scale. More-
1m
2m
2n
I
NH2
NH2
I
1n
Continued on next Column:

1242 Bull. Chem. Soc. Jpn. Vol. 85, No. 11 (2012)
Synthetic Protocol for Iodination of Organic Substrates
over, these reagents are environmentally acceptable. Notably,
the ester functionality does not undergo hydrolysis under the
reaction conditions although the medium is acidic. Good yield,
high selectivity, use of cost effective reagents, and mild and
environmentally benign reaction conditions are some major
advantages of this protocol.
Ethyl 2-Iodo-3-oxo-3-phenylpropanoate (2f): Yellow oil.
1
IR (KBr): 2931, 1675, 1272, 1002 cm¹1. H NMR (400 MHz,
CDCl3): ¤ 1.22 (t, J = 7.2 Hz, 3H), 4.24 (q, J = 7.2 Hz, 2H),
5.92 (s, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.57 (t, J = 7.6, 1H),
7.96 (d, J = 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): ¤ 14.0,
24.2, 63.5, 129.1, 129.3, 133.1, 134.3, 166.7, 189.4. Anal.
Calcd for C11H11IO3 (318.10): requires C, 41.53; H, 3.49%.
Found C, 41.42; H, 3.39%.
Experimental
Typical Procedure for Iodination. Vanadyl acetylaceto-
nate (0.053 g, 0.2 mmol) was taken in 2 mL of water at ice-bath
temperature (0-5 °C). Then, 0.5 mL of H2O2 (4.4 mmol) was
added slowly to it and kept stirring at the same temperature.
The solution becomes yellow after 10 min and subsequently
the substrate was added to it by dissolving in 3 mL of ethyl
acetate followed by NaI (0.3 g, 2.0 mmol) solution by taking
into 1.5 mL of water. The solution becomes dark brown
instantly. After completion of the reaction, it was extracted
with ethyl acetate (3 © 25 mL) and the organic layer was
washed with 10% sodium thiosulfate solution to remove
unreacted iodine. Finally, the organic layer was washed with
water and dried over sodium sulfate. The solvent was evapo-
rated under vacuum and pure product was obtained 2a as
yellow oil in 91% yield.
Ethyl 1-Iodo-2-oxocyclohexanecarboxylate (2g): Yellow
oil. IR (KBr): 2941, 2868, 1722, 1449, 1235, 1122, 1092,
1018 cm¹1. 1H NMR (400 MHz, CDCl3): ¤ 1.28 (t, J = 7.2 Hz,
3H), 1.67-1.74 (m, 2H), 1.75-1.80 (m, 1H), 1.94-1.98 (m, 1H),
2.25-2.32 (m, 1H), 2.47-2.54 (m, 1H), 2.91-2.96 (m, 2H), 4.27
(q, J = 7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3): ¤ 13.9,
24.8, 27.3, 38.3, 43.3, 53.3, 63.1, 169.5, 200.0. Anal. Calcd for
C9H13IO3 (296.10): requires C, 36.51; H, 4.43%. Found C,
36.38; H, 4.33%.
Ethyl 1-Iodo-2-oxocyclopentanecarboxylate (2h): Yel-
¹1
low oil. IR (KBr): 2973, 1745, 1256, 1180, 1132, 1020 cm
.
1H NMR (400 MHz, CDCl3): ¤ 1.29 (t, J = 7.2 Hz, 3H), 2.07-
2.14 (m, 2H), 2.35-2.53 (m, 4H), 4.26 (dq, J = 7.2, 0.6 Hz,
2H). 13C NMR (100 MHz, CDCl3): ¤ 14.0, 20.0, 35.1, 40.3,
43.6, 63.3, 168.1, 207.1.
2-Iodo-1-phenylbutane-1,3-dione (2a):
Yellow oil. IR
Diethyl 2-Iodomalonate (2i):
2984, 1745, 1630, 1372, 1300, 1236, 1136, 1099, 1024 cm
Yellow oil. IR (KBr):
¹1
(KBr): 3388, 3066, 1687, 1599, 1448, 1355, 1221, 1185, 1124,
.
1
1018 cm¹1. H NMR (400 MHz, CDCl3): ¤ 2.56 (s, 3H), 5.97
1H NMR (400 MHz, CDCl3): ¤ 1.30 (t, J = 7.2 Hz, 3H), 4.32
(q, J = 7.2 Hz, 2H), 4.80 (s, 1H). 13C NMR (100 MHz, CDCl3):
¤ 14.0, 63.5, 90.4, 168.4. Anal. Calcd for C7H11IO4 (286.06):
requires C, 29.39; H, 3.88%. Found C, 29.23; H, 3.71%.
Ethyl 2-Benzyl-2-iodo-3-oxobutanoate (2j): Yellow oil.
IR (KBr): 2978, 1711, 1356, 1309, 1236, 1187, 1083, 1015
(s, 1H), 7.51 (t, J = 7.6 Hz, 2H), 7.64 (t, J = 7.6 Hz, 1H), 7.98
(d, J = 7.6 Hz, 2H). 13C NMR (100 Hz, CDCl3): ¤ 27.3, 33.0,
129.3, 129.4, 133.9, 134.6, 191.2, 198.9. Anal. Calcd for
C10H9IO2 (288.08): requires C, 41.69; H, 3.15%. Found C,
41.51; H, 3.06%.
2-Iodo-1,3-diphenylpropane-1,3-dione (2b): White solid;
mp 107-108 °C. (Lit.17a 108-109 °C). IR (KBr): 2957, 1688,
1662, 1594, 1446, 1289, 1240, 1182, 994, 979 cm¹1. H NMR
(400 MHz, CDCl3): ¤ 6.95 (s, 1H), 7.48 (t, J = 8.0 Hz, 4H),
7.61 (t, J = 7.6 Hz, 2H), 8.00 (d, J = 7.6 Hz, 4H). 13C NMR
(100 MHz, CDCl3): ¤ 34.1, 129.3, 129.5, 133.4, 134.4, 190.3.
Anal. Calcd for C15H11IO2 (350.15): requires C, 51.45; H,
3.17%. Found C, 51.32; H, 3.09%.
1
cm¹1. H NMR (400 MHz, CDCl3): ¤ 1.20 (t, J = 7.6 Hz, 3H),
2.47 (s, 3H), 3.54 (d, J = 14.4 Hz, 1H), 3.67 (d, J = 14.4 Hz,
1H), 4.17 (q, J = 7.2 Hz, 2H), 7.17-7.26 (m, 5H). 13C NMR
(100 MHz, CDCl3): ¤ 13.9, 26.9, 44.4, 54.5, 63.4, 127.6,
128.4, 130.4, 136.4, 168.4, 198.2. Anal. Calcd for C13H15IO3
(346.16): requires C, 45.11; H, 4.37%. Found C, 45.01; H,
4.26%.
Ethyl 2-Ethyl-2-iodo-3-oxobutanoate (2k): Yellow oil. IR
(KBr): 3418, 2979, 2044, 1714, 1457, 1358, 1229, 1122,
1022 cm¹1. 1H NMR (400 MHz, CDCl3): ¤ 0.96 (t, J = 7.2 Hz,
3H), 1.28 (t, J = 7.6 Hz, 3H), 2.17 (q, J = 7.2 Hz, 2H), 2.45
(s, 3H), 4.25 (q, J = 7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3):
¤ 12.3, 14.0, 26.0, 32.5, 56.5, 63.3, 168.8, 198.2. Anal. Calcd
for C8H13IO3 (284.09): requires C, 33.82; H, 4.61%. Found C,
33.69; H, 4.53%.
4-Iodoaniline (2l): White solid; mp 60-62 °C (Lit.25 62-
63 °C). IR (KBr, cm¹1): 3405 (-NH2), 3297 (-NH2). H NMR
(400 MHz, CDCl3): ¤ 3.68 (brs, 2H), 6.47 (d, J = 8.4 Hz,
2H), 7.41 (d, J = 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3):
¤ 79.5, 117.5 (2C), 138.1 (2C), 146.2. Anal. Calcd for C6H6NI
(219.02): requires C, 32.90; H, 2.76; N, 6.40%. Found C,
32.71; H, 2.55; N, 6.26%.
1
3-Hydroxy-2-iodo-5,5-dimethylcyclohex-2-enone
(2c):
White solid; mp 154-155 °C. (Lit.17c 166-167 °C). IR (KBr):
¹1
3448, 1624, 1574, 1317, 1000 cm
.
1H NMR (400 MHz,
CDCl3): ¤ 1.15 (s, 6H), 2.48 (s, 4H). 13C NMR (100 MHz,
DMSO): ¤ 27.5, 32.3, 46.6, 76.7, 184.5. Anal. Calcd for
C8H11IO2 (266.08): requires C, 36.11; H, 4.17%. Found C,
36.01; H, 4.06%.
3-Hydroxy-2-iodocyclohex-2-enone (2d): White solid; mp
138-139 °C. IR (KBr): 3105, 1645, 1580, 1368, 1315, 1190,
1
1
1144, 1066, 956 cm¹1. H NMR (400 MHz, CDCl3 + DMSO):
¤ 1.97 (quint, J = 6.0 Hz, 2H), 2.61 (t, J = 6.0 Hz, 4H).
13C NMR (100 MHz, DMSO): ¤ 20.9, 33.3, 78.6, 185.6. Anal.
Calcd for C6H7IO2 (238.02): requires C, 30.28; H, 2.96%.
Found C, 30.16; H, 2.88%.
tert-Butyl 2-Iodo-3-oxobutanoate (2e):
(KBr): 2981, 1731, 1639, 1371, 1251, 1154 cm
Yellow oil. IR
4-Iodo-N-methylaniline (2m): Colorless Liquid. IR (KBr,
¹1
1
.
1H NMR
cm¹1): 3422 (-NH2); H NMR (400 MHz, CDCl3): ¤ 2.72 (s,
(400 MHz, CDCl3): ¤ 1.48 (s, 9H), 2.51 (s, 3H), 4.94 (s, 1H).
13C NMR (100 MHz, CDCl3): ¤ 26.3, 27.8, 28.2, 84.3, 165.7,
197.9. Anal. Calcd for C8H13IO3 (284.09): requires C, 33.82;
H, 4.61%. Found C, 33.74; H, 4.53%.
3H), 3.67 (brs, 1H), 6.31 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.8
Hz, 2H). 13C NMR (100 MHz, CDCl3): ¤ 30.7, 77.9, 114.8 (2C),
137.9 (2C), 149.0. Anal. Calcd for C7H8NI (233.05): requires C,
36.08; H, 3.46; N, 6.01%. Found C, 36.26; H, 3.54; N, 6.14%.

A. T. Khan et al.
Bull. Chem. Soc. Jpn. Vol. 85, No. 11 (2012) 1243
and Applications, ed. by M. J. Welch, C. S. Redvanly, Wiley,
Chichester, 2003. doi:10.1002/0470846380.
4-Ethyl-2-iodoaniline (2n): Colorless Liquid. IR (KBr,
cm¹1): 3398 (-NH2), 3299 (-NH2). 1H NMR (400 MHz,
CDCl3): ¤ 1.17 (t, J = 7.6 Hz, 3H), 2.50 (q, J = 7.6 Hz, 2H),
3.96 (brs, 2H), 6.69 (d, J = 8.4 Hz, 1H), 6.98 (dd, J1 = 2.0,
J2 = 8.0 Hz, 1H), 7.48 (d, J = 1.6 Hz, 1H). 13C NMR (100
MHz, CDCl3): ¤ 16.0, 27.6, 84.5, 114.9, 129.0, 136.2, 138.1,
144.6. Anal. Calcd for C8H10NI (247.08): requires C, 38.89;
H, 4.08; N, 5.67%. Found C, 38.71; H, 3.99; N, 5.54%.
4-Iodo-3,5-dimethyl-1H-pyrazole (2p): White solid, mp
7
8
9
A. Butler, J. V. Walker, Chem. Rev. 1993, 93, 1937.
H. Vilter, Phytochemistry 1984, 23, 1387.
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10 A. Butler, J. N. Carter-Franklin, Nat. Prod. Rep. 2004, 21,
180.
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126, 15060.
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13 S. Stavber, M. Jereb, M. Zupan, Synthesis 2008, 1487.
14 a) C. J. Rieder, K. J. Winberg, F. G. West, J. Org. Chem.
2011, 76, 50. b) M. Dey, K. Deb, S. S. Dhar, Chin. Chem. Lett.
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138-140 °C (Lit.28b 134-136 °C). IR (KBr): 3165, 3067, 3030,
¹1
2917, 2830, 1577, 1412, 1305, 1164, 1077, 1034 cm
.
1H NMR (400 MHz, CDCl3): ¤ 2.24 (s, 6H), 4.27 (s, 1H).
13C NMR (100 MHz, CDCl3): ¤ 13.1, 62.7, 146.5. Anal. Calcd
for C5H7IN2 (222.02): requires C, 27.05; H, 3.18; N, 12.62%.
Found C, 26.92; H, 3.11; N, 12.46%.
4-Iodo-3-methyl-5-phenyl-1H-pyrazole (2q): White solid,
mp 117-120 °C (Lit.28b 113-115 °C). IR (KBr): 3173, 3067,
2929, 1567, 1448, 1291, 1269, 1179, 1116, 1045, 967,
1
915 cm¹1. H NMR (400 MHz, CDCl3): ¤ 2.26 (s, 3H), 7.39-
7.46 (m, 3H), 7.70-7.73 (m, 2H). 13C NMR (100 MHz, CDCl3):
¤ 12.7, 60.6, 128.4, 128.6, 128.7, 131.9, 146.4, 149.8. Anal.
Calcd for C10H9IN2 (284.10): requires C, 42.28; H, 3.19; N,
9.86%. Found C, 42.17; H, 3.08, N, 9.69%.
(E)-1-(2-Hydroxy-3-iodo-4,6-dimethoxyphenyl)-3-(3,4-di-
methoxyphenyl)prop-2-en-1-one (2r):
Yellow solid, mp
152 °C. IR (KBr, cm¹1): 3445 (-OH), 1624 (-C=O). H NMR
(400 MHz, CDCl3): ¤ 3.94 (s, 3H), 3.95 (s, 3H), 3.98 (s, 3H),
4.00 (s, 3H), 6.05 (s, 1H), 6.90 (d, J = 8.0 Hz, 1H), 7.12
(s, 1H), 7.22 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 15.2 Hz, 1H),
7.81 (d, J = 15.6, 1H). 13C NMR (100 MHz, CDCl3): ¤ 56.1,
56.2, 56.3, 56.6, 87.2, 91.4, 106.9, 110.7, 111.4, 123.0, 124.8,
128.5, 143.8, 149.3, 151.5, 163.8, 164.3, 165.8, 192.4. Anal.
Calcd for C19H19IO6 (470.26): requires C, 48.53; H, 4.07%.
Found C, 48.71; H, 4.18%.
1
16 A. J. Fatiadi, J. Chem. Soc. D 1970, 11.
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SA is thankful to UGC, New Delhi, India for their Senior
Research Fellowship. The authors are also grateful to the
Director, IIT Guwahati for providing general facilities to carry
out our research work. We are also thankful to the referees for
their valuable comments and suggestions.
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Handbook of Radiopharmaceuticals: Radiochemistry