Efficient α-iodination of carbonyl compounds under solvent-free conditions using microwave irradiation

Article abstract of DOI:10.1055/s-2003-37523

Direct conversion of carbonyl compounds into α-iodocarbonyl compounds has been successfully achieved under solvent-free microwave irradiation conditions using N-iodosuccinimide and p-toluenesulfonic acid.

Full text of DOI:10.1055/s-2003-37523

LETTER
507
Efficient a-Iodination of Carbonyl Compounds Under Solvent-Free
Conditions Using Microwave Irradiation
E
J
fficient
α
o
-Iodination
no f Carbonyl
C
g
ompounds Chan Lee,* Yong Hun Bae
Department of Chemistry, Chung-Ang University, Seoul 156-756, Korea
Fax +82(2)8254763; E-mail: jclee@cau.ac.kr
Received 27 January 2003
developing a new direct method for α-iodination of ke-
tones promoted by microwave irradiation under solvent-
free reaction conditions. Therefore, we report herein a
convenient method for the preparation of α-iodocarbonyl
compounds from the reaction of carbonyl compounds
with NIS in the presence of p-toluenesulfonic acid (PT-
SA) under solvent-free microwave irradiation conditions
Abstract: Direct conversion of carbonyl compounds into α-io-
docarbonyl compounds has been successfully achieved under
solvent-free microwave irradiation conditions using N-iodosuccin-
imide and p-toluenesulfonic acid.
Key words: carbonyl, halides, iodine, ketones, microwave
(
Scheme 1).
The preparation of α-iodoketones and their applications
as reaction intermediates have attracted considerable at-
O
O
1
–4
tention in various organic transformations. A number of
indirect methods are available for the preparation of α-io-
doketones, which include the reactions of enol acetates or
enol silyl ethers with appropriate iodinating agents such as
NIS/PTSA
R'
R'
R
R
MWI, 1 - 1.2 m
I
5
6
Scheme 1
iodine–copper(II) nitrate and iodine–silver acetate. Di-
rect α-iodination of ketones can be achieved by the reac-
tion of ketones with several reagent systems which Microwave irradiation to the neat mixture of ketone, NIS
7
include iodine–cerium(IV) ammonium nitrate, potassium (1.2 equiv), and PTSA (1.2 equiv) in household micro-
8
iodide–potassium iodate–sulfuric acid, and iodine–sele- wave oven at its full power (700 W) afforded the corre-
9
16
nium dioxide . However, the required harsh reaction con- sponding α-iodoketone. All of the reactions studied
ditions, long reaction times, or tedious work-up proceeded smoothly to give the corresponding α-iodoke-
procedures in most of the above-mentioned methods limit tones with high yields in very short reaction times (1–1.2
their practical utilities in organic synthesis. In addition, far min) as shown in the Table 1. Aromatic ring iodination of
less attention has been given to the conversion of 1,3-di- the aromatic ketones was not detected at all in the reac-
carbonyl compounds to the corresponding 2-iodo-1,3-di- tions investigated. We also examined the iodination of a
1
0–12
carbonyl compounds.
Among other useful reagents, number of 1,3-dicarbonyl compounds to the correspond-
use of N-iodosuccinimide (NIS) for the iodination of var- ing 2-iodo-1,3-dicarbonyl compounds under present reac-
ious substrates has been received significant attention and tion conditions and the reactions proved to be highly
1
3–15
the results are reported in a couple of literature.
How- successful as given in entries 10–13. Preparation of di-
ever, application of NIS for the preparation of α-iodoke- alkyl iodomalonates from dialkyl malonates has been
tones has been very sparse. In this context, to our best known to be very difficult and there are only a few meth-
knowledge, there has been only one report that briefly de- ods reported to date.1 When we applied present method
scribed the α-iodination of acetophenone using NIS–tri- for the iodination of dialkyl malonates, the corresponding
fluoromethanesulfonic acid.14 However, practical dialkyl iodomalonates were obtained in very high yields
application of this method should be limited because of (entries 12 and 13). Moreover, synthetically useful 2-io-
0,11
the highly fuming nature of trifluoromethanesulfonic ac- doindanone and 2-iodotetralone were also obtained in
9
id.
high yields (entries 14–16). Formation of α,α-diiodinat-
ed carbonyl products was not observed in all cases studied
in the Table 1. Attempts to react carbonyl compounds
with NIS without use of PTSA were unsuccessful to give
only unchanged starting materials. Hence, it is reasonable
to explain that the enhanced reactivity of NIS came from
the increase of enol contents of carbonyl compounds by
acid promoted protonation of carbonyl compounds as well
as the formation of protonated NIS with PTSA as suggest-
ed in analogous acid promoted reaction of carbonyl-con-
jugated alkynes with NIS.15
Recently, organic reactions promoted by microwave irra-
diation under solvent-free conditions received much at-
tention due to the advantages over conventional methods
in terms of rapid reaction rates, improved yields, and en-
vironmentally benign reaction conditions.
As part of a program aimed at developing facile method
for the preparations α-haloketones, we were interested in
Synlett 2003, No. 4, Print: 12 03 2003.
Art Id.1437-2096,E;2003,0,04,0507,0508,ftx,en;U01003ST.pdf.
©
Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

5
08
J. C. Lee, Y. H. Bae
LETTER
Table 1 Microwave Irradiation Promoted Preparation of α-Iodocar-
bonyl Compounds
ditions. The advantages of present method in light of very
fast reactions, solvent-free conditions, and high yields
should make this protocol as a useful alternative to exist-
ing methods.
Entry Substrate
Product
Yield
%)a
(
1
2
3
4
5
6
7
8
9
0
1
2
3
PhCOCH3
PhCOCH2I
84
90
82
87
75
78
Acknowledgement
p-CH C H COCH
p-CH C H COCH I
3
6
4
3
3
6
4
2
We thank the KOSEF (R01-1999-00036) for financial support of
this work.
p-CH OC H COCH
p-CH OC H COCH I
3 6 4 2
3
6
4
3
p-ClC H COCH
p-ClC H COCH I
6 4 2
6
4
3
References
p-NO C H COCH
p-NO C H COCH I
2 6 4 2
2
6
4
3
(
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3919.
PhCOCH CH
PhCOCHICH3
2
3
(
(
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p-CH C H COCH CH
p-CH C H COCHICH 90
3 6 4 3
3
6
4
2
3
p-CH OC H COCH CH p-CH OC H COCHICH 82
3
6
4
2
3
3
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4
3
(
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p-ClC H COCH CH
p-ClC H COCHICH
3
83
84
82
91
78
6
4
2
3
6
4
(
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1
1
1
1
CH COCH COOEt
CH COCHICOOEt
(6) Rubottom, G. M.; Mott, R. C. J. Org. Chem. 1979, 44, 1731.
3
2
3
(
(
7) Horiuchi, C. A.; Kiji, S. Chem. Lett. 1988, 31.
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PhCOCH COOEt
PhCOCHICOOEt
2
MeOCOCH COOMe
MeOCOCHICOOMe
EtOCOCHICOOEt
O
2
(
EtOCOCH COOEt
2
(
(
10) Curran, D. P.; Chen, M.-H.; Spletzer, E.; Seong, C. M.;
Chang, C.-T. J. Am. Chem. Soc. 1989, 111, 8872.
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O
1
1
4
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76
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(12) Urasaki, I.; Ogata, Y. J. Chem. Soc., Perkin Trans. 1 1975,
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I
1
(
(
(
O
O
2
I
15) Heasley, V. L.; Shellhamer, D. F.; Chappell, A. E.; Cox, J.
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O
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I
(
16) General experimental procedure: A neat mixture of ketone,
1
NIS (1.2 equiv), and p-toluenesulfonic acid monohydrate
(1.2 equiv) was placed in a glass test tube. The test tube
containing reaction mixture was inserted in an alumina bath
inside a household microwave oven and irradiated (700 W)
three to four times for a period of 20 s with 10 s interval.
After cooling down, the reaction mixture was extracted with
dichloromethane (2 × 25 mL) and washed with water (40
mL). The dichloromethane layer was separated and dried
a
Isolated yields.
In conclusion, we have devised a new convenient method
for the synthesis of α-iodocarbonyl compounds directly
from carbonyl compounds using the combination of NIS
and PTSA under solvent free microwave irradiation con-
over MgSO . After evaporation of the solvent, the residue
4
was purified by flash column chromatography (SiO2,
dichloromethane) to give pure α-iodoketone.
Synlett 2003, No. 4, 507–508 ISSN 0936-5214 © Thieme Stuttgart · New York