Aerobic oxidative iodination of ketones catalysed by sodium nitrite "on water" or in a micelle-based aqueous system

Article abstract of DOI:10.1039/b902230a

Selective and efficient aerobic oxidative iodination of ketones in aqueous media was achieved by using molecular iodine as the source of iodine atoms, air as the terminal oxidant, sodium nitrite (NaNO₂) as the catalyst and H₂SO₄

Full text of DOI:10.1039/b902230a

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PAPER
www.rsc.org/greenchem | Green Chemistry
Aerobic oxidative iodination of ketones catalysed by sodium nitrite
“on water” or in a micelle-based aqueous system†
Gaj Stavber,a Jernej Iskra,b Marko Zupana and Stojan Stavber*b
Received 3rd February 2009, Accepted 12th May 2009
First published as an Advance Article on the web 8th June 2009
DOI: 10.1039/b902230a
Selective and efficient aerobic oxidative iodination of ketones in aqueous media was achieved by
using molecular iodine as the source of iodine atoms, air as the terminal oxidant, sodium nitrite
(NaNO2) as the catalyst and H2SO4 as the activator of the overall catalytic process. The efficiency
of the reaction, resulting in a-iodo ketones, was significantly improved in an aqueous solution of
the anionic amphiphile sodium dodecyl sulfate (SDS), capable of self-assembly into micelle-based
aggregates, thus forming a reactive micellar system. The regioselectivity of iodofunctionalization
of aryl methyl ketones was regulated by the reaction medium used: in an aqueous micelle-based
system the methyl group was iodinated, while in anhydrous MeCN aryl iodides were formed with
high selectvity.
and more efficient technologies for oxidative transformations of
Introduction
organic molecules. The potential inconvenience for performing
organic reactions in water is very often connected with the
incompatibility of organic molecules with water, although some
organic reactions can be carried out simply by stirring the
neat reactants in an aqueous suspension described under the
term “on water” conditions.5 The addition of amphiphiles
in water ordinarily cause their self-association into micelles
which is driven by the hydrophobic effect,6 well described by
solvation thermodynamics that play a role in the overlap of the
hydratation shells of the hydrophobic parts of the molecules on
self-assembly. Accommodation of insoluble organic compounds
in such a media has been promoted and reviewed as a possible
approach to performing organic reactions in water.7 Reactions
in micellar systems,8 including the micellar catalysis approach
of using acid-surfactant-combined catalysts,9 have considerably
extended organic chemistry in water.
Iodinated organic compounds and methods for selective iodi-
nation have received significant attention among the scientific
community. Iodo-substituted organic compounds are impor-
tant precursors and synthons in organic synthesis, above all
in carbon-carbon, carbon-oxygen and carbon-nitrogen bond
formation, for their useful properties reflected in medicine
as contrast agents or radioactively labelled markers and fur-
ther, many of them are biologically active.1 Aryl iodides and
a-iodo ketones are especially convenient tools for the mentioned
purposes. The most logical choice of iodinating agent for
introduction of iodine atoms into organic compounds is the use
of molecular iodine (I2) or the iodide anion (I-), but since I2 is
very often poorly reactive, substantial efforts have been invested
in development of efficient, mild and selective methods for direct
introduction of an iodine atom into organic molecules. Synthetic
strategies for electrophilic iodination of organic compounds
using I2 or I- have been reviewed recently2 and it is clear that
oxidative iodination using these two sources of iodine atoms
in combination with environmentally benign and atom efficient
oxidants in non-volatile or non-toxic solvents seems to be the
most promising methodology from the viewpoint of the green
approach to organic synthesis.
Water-based aerobic catalytic systems received significant
attention and made much progress in the past few years, but
they were used mainly for aerobic oxidation of alcohols,10
first promoted by Sheldon and co-workers11 using a recyclable
water-soluble palladium complex catalyst under 30-bar air
pressure. Various transition-metal catalysts were used for these
purposes,12 while very recently a catalyst-free procedure of aero-
The use of H2O2 or even O2 as the most environmentally
benign oxidants3 and water as the reaction medium4 represent
promising options in the constant search for cheaper, cleaner
bic “on and in water” oxidation of aldehydes was reported.13
A
metal-free catalytic system for aerobic oxidation of alcohols was
recently promoted using sodium nitrite (NaNO2) in combination
with an efficient co-catalyst in an organic solvent14 or aqueous
media,15 performed in an air filled autoclave. Sodium nitrite is a
simple, inexpensive inorganic compound with an unique redox
property, which under acidic conditions releases nitric oxide
(NO), known as a highly reactive unstable species oxidisable
with molecular oxygen to nitrogen dioxide (NO2), which is then
involved in further oxidation processes, releasing NO and thus
continuing the cycle.14–16 This ability of NaNO2 as a catalyst
has been taken advantage of aerobic oxidative halogenation
of organic compounds,17 but organic solvents were always
aFaculty of Chemistry and Chemical Technology, University of Ljubljana,
Asˇkercˇeva 5, 1000, Ljubljana, Slovenia.
E-mail: gaj.stavber@fkkt.uni-lj.si; Tel: +386 1 241 9100
bJozˇef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia. E-mail:
stojan.stavber@ijs.si; Fax: +386 1 423 5400; Tel: +386 1 477 36660
† Electronic supplementary information (ESI) available: 10 mmol scale
synthesis procedures of compounds 4 and 10a and isolation of products
without using organic solvents; indentification data for known com-
1
pounds 2, 6, 8, 10b, 12, 20, 10c, and 21; H and 13C NMR spectra of
unknown compounds 10d, 22, 10e, and 23. See DOI: 10.1039/b902230a
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Table 1 Effect of reaction conditions on aqueous aerobic oxidative
used as the reaction medium. This leads us to the challenging
question of if it is possible to perform selective and efficient
catalytic aerobic oxidative halogenation of organic compounds
successfully in water. In a view of our continuing efforts to
develop new, environmentally benign, synthetic methods for
selective halogenation of organic compounds,17b–d,18 we now
report the selective and efficient iodination of various types of
ketones by an aerobic oxidative process catalyzed by the catalyst
sodium nitrite in an aqueous micellar system.
a
iodination of acetophenone 1 catalyzed by NaNO2
H2SO4
NaNO2
Conv. of 1
to 2 (%)b
Entry Aqueous medium (mmol) (mol%) T (◦C)
1
2
3
4
5
6
7
8
9
Pure H2O
Pure H2O
Pure H2O
0.25
0.25
0.5
5
5
12
12
4
10
12
12
12
12
12
30
60
60
60
60
60
60
60
30
60
60
30
55
74
84
62
79
100[91]
76
53
Results and discussion
8.1 ¥ 10-3 M SDS c 0.5
0.1 M SDS d
0.1 M SDS
0.1 M SDS
0.1 M SDS
0.1 M SDS
0.1 M SDS
0.1 M SDSf
0.5
0.5
0.5
0.25
0.5
Oxidative iodination of organic compounds under an oxygen
atmosphere was introduced by Radner who used lower nitrogen
oxide species in order to catalyze the aerobic oxidative iodofunc-
tionalisation of arenes and cyclohexene in organic solvents.19
Later, only a few examples of aerobic oxidative iodination have
been described and only arenes were efficiently iodinated with
molecular iodine under an oxygen atmosphere using bismuth
(III) salts20 or polyoxometallate21 catalysts in acetonitrile or
nitrobenzene as reaction medium. We have recently demon-
strated the efficient and selective aerobic oxidative iodination
of arenes, carbonyls, alkenes and alkynes with molecular iodine
or iodide using sodium nitrite as catalyst and air as the terminal
oxidant performing the reactions under acidic conditions in
organic solvents.17b,c To the best of our knowledge, there is
no previous reports on an aerobic oxidative halogenation of
organic compounds in water as reaction medium and this was a
very compelling reason for further investigations of the NaNO2-
based catalytic system for aerobic oxidative iodination of organic
molecules.
e
10
11
/
82
74
1
a Reaction conditions: 1 (1 mmol); I2 (0.5 mmol) or KI (1.05 mmol), 96%
H2SO4 (0.25–1 mmol); NaNO2 (4–12 mol%); solvent (5 mL); air balloon
(1 L); stirring (500 rpm) for 12 h at T = 30–60 ◦C. b Determined from 1H
NMR spectra of crude reaction mixture, the value in bracket refers to
isolated yield. c Critical micelle concentration (cmc) of SDS (0.04 mmol
of SDS in 5 mL of H2O, 8.1 ¥ 10-3 M). d Above cmc of SDS (0.5 mmol
of SDS in 5 mL of H2O, 0.1 M). e 1 equiv. of HClO4 (pKa = -7) was
used as acid. f KI was used as an iodine atom source.
conversion of 1 to 2 by adding to the reaction system the anionic
amphiphile sodium dodecyl sulfate (SDS), whose micellisation
in aqueous media was well explored.22 The addition of SDS in
the amount required for critical micelle concentration (CMC;
o
8.1 ¥ 10-3 M at 25 C)8,27 increased the conversion of starting
We started our investigation by studying the aqueous aerobic
oxidative iodination of acetophenone 1 as a model substrate.
Following the overall stoichiometric equations for aerobic
oxidative iodination of organic compounds using I- (1), the
presence of at least one equivalent of protons is crucial for the
reaction, while using I2 (2) the presence of an acid would not
be necessary. However, the presence of an acid is in both cases
indispensable for the activation of the NaNO2 catalytic oxidative
cycle, thus tuning the overall process.
material (entry 4) in comparison with the reaction in pure
water medium, while the complete iodofunctionalisation to 2
was achieved in a 0.1 M SDS micellar aqueous solution at
60 ◦C in the presence of 0.5 mmol of H2SO4 and 12 mol%
of NaNO2 (entry 7) using molecular iodine as the reagent. The
experiments also revealed that the presence of a strong acid like
H2SO4 (pKa = -10) is essential and beneficial for the efficiency
of the reaction since the use of the same amount of the weaker
acid HClO4 (pKa = -7) was found to be insufficient (entry 10)
to successfully tune the reactivity of the aerobic system. The
effect of the source of the iodine atom on aerobic oxidative
iodination of target compound 1 was also studied and results
showed clearly that iodination using I2 was more efficient than
using iodide anione (I-) as the iodine source (entry 11). The
iodinating system I2/air/NaNO2(cat.)/H2SO4 was thus found
to be the right choice for efficient aerobic oxidative iodination
of the model substrate acetophenone 1 in a SDS micelle-based
aqueous system and this was then used in all further experiments.
It is known from the literature that in the case of reactions
performed “on water” stirring of the reaction mixture has
a crucial effect on the rate and efficiency of these reactions
and that liquid substrates are usually more reactive than solid
ones.5c–g Liquid substrates, or those solids with melting points
lower than the reaction temperature, are disrupted by vigorous
stirring into small droplets, forming a suspension having a
much larger active surface thus enabling efficient interactions
between reactants on the surface of water. In the case of solid
substrates, vigorous stirring is even more important, but the
S–H + Iꢀ + 0.5 O2 + H≈ → S–I + H2O
(1)
(2)
2 S–H + I2 + 0.5 O2 → 2 S–I + H2O
In a typical mmol-scale experiment, to a magnetically stirred
dispersion of acetophenone 1 in water contained in a 50 mL
vessel, I2 or KI and acid was added, followed by addition of
a catalytic amount of NaNO2. The reaction vessel was closed
with a balloon (1 L) filled with air and the reaction mixture
magnetically stirred for 12 hours. The reaction parameters
(iodine source, acid and its amount, amounts of NaNO2 catalyst
and reaction temperature) were varied and the conversion of ace-
tophenone 1 to its iodinated derivative 2-iodo-1-phenylethanone
2 analyzed. As we have already reported, MeCN or EtOH
could be appropriate reaction media for this transformation;17b,c
though the efficiency of the reaction in pure water decreased
considerably (entry 1, Table 1), it was improved by increasing the
reaction temperature and the amounts of added acid and catalyst
(entries 2,3). We found it possible to succeed in quantitative
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Table 2 Effect of stirring on the efficiency of aerobic oxidative iodina-
Table 3 Aerobic oxidative iodination of ketones catalysed by NaNO2
a
tion of 3,4-dihydro-2H-naphthalen-1-one 3 catalyzed by NaNO2
on pure water (A) or in SDS micelle-based aqueous system (B)a
Yieldb (%)
Entry Iodotransformation
1
Time (h) A
B
2
3
69 100[85]c
Aqueous
Entry medium
Time (h) Stirring (rpm) Conv. of 3 to 4 (%)b
1
2
3
4
5
6
Pure H2O
0.5
24
0.5
0.5
24
0.5
0
0
700
0
0
500
24
41
71
58
83
100[90]
2
67 100[84]
0.1 M SDS
a Reaction conditions: 3 (1 mmol); I2 (0.5 mmol), 96% H2SO4 (0.5 mmol);
NaNO2 (12 mol%); pure water or 0.1 M aqueous SDS (5 mL); air balloon
(1 L); magnetic stirring (0–700 rpm); T = 60 ◦C. b Determined from 1H
NMR spectra of crude reaction mixture, the value in bracket refers to
isolated yield.
3
4
5
6
7
8
a: 4-methoxy
3.5
1
4
4
4
70 100[90]
81 100[90]
80 100[73]
80 100[80]
80 100[85]
84 100[93]
b: 2,4-dimethoxy
c: 2,6-dimethoxy
d: 3,5-dimethoxy
e: 2,4,6-trimethoxy
efficiency of interactions also depends on the size of the solid
particles and their shape.7d The effect of stirring of the reaction
mixture on the efficiency of aerobic oxidative iodination with the
I2/air/NaNO2(cat)/H2SO4 system in micellar aqueous media
or “on water” is presented in Table 2. Vigorous stirring was
found to be crucial for iodotransformation of liquid model
substrate 3,4-dihydro-2H-naphthalen-1-one 3 “on water” and
a rate of 700 rpm gave the optimal result (entry 3). Reaction
in 0.1 M SDS aqueous micellar medium magnetically stirred
at 500 rpm (entry 6) resulted in the quantitative formation of
2-iodo-3,4-dihydro-2H-naphthalen-1-one 4, while the effect of
stirring was less exspressed (entries 4 and 5) than in the case
of “on water” iodotransformations (entries 1 and 2). These two
stirring intesities were thus applied in all further experiments.
Encouraged by these results and experimental insights for aer-
obic oxidative iodination of model substrates 1 and 3, we applied
the catalytic reaction system of I2/air/NaNO2(cat.)/H2SO4
to the iodination of a variety of substituted ketones in the
micelle-based SDS aqueous medium, comparing the efficiency
to that of transformations on water. The results are pre-
sented in Table 3. We started our evaluation with cycloalkyl
ketone 4-tert-butyl-cyclohexanone 5 which was readily and
quantitatively transformed to a mixture of 2-iodo substituted
isomeric products 6 (anti/syn ratio 2:1) in the micelle-based
SDS aqueous media, while the transformation was found to be
less efficient on water (entry 1). Similar results were obtained
in the case of the aerobic oxidative iodination of acyclic alkyl
substituted ketone 5-nonanone 7 to 4-iodo-5-nonanone 8 (entry
2). Aerobic oxidative iodination with the catalytic iodinating
system developed proved to be highly regiospecific in the
case of substrates bearing an activated aromatic ring. 1-(4-
Methoxy-phenyl)-ethanone 9a was selectively transformed into
its a-iodo functionalized derivative 10a with excellent yield
(entry 3). It seems that the SDS aqueous micelle as medium
directs the regioselectivity of aerobic oxidative iodination of
a series of methoxy substituted aryl methyl ketones 10b-e
and 11 (entries 4 to 8) to the a-carbonyl position, since in
all these cases side chain iodofunctionalization was found
0.2
9
4
4
73 100[80]
10
11
57 100[82]
71d 100[83]
12
12
8
48 90[81]
a Reaction conditions: Substrate (1 mmol), pure H2O (5 mL; conditions
A) or 0.1 M aqueous SDS (5 mL; conditions B), I2 (127 mg, 0.5 mmol),
96% H2SO4 (47 mg, 0.5 mmol), NaNO2 (8.4 mg, 0.12 mmol), air balloon
(1 L), stirring at 700 rpm for A and 500 rpm for B conditions at 60 ◦C.
b Conversion of starting material to iodinated product determined from
1H NMR spectra of crude reaction mixture; values in square parentheses
refer to isolated pure products obtained on a silica column. c Mixture of
anti and syn products in the relative ratio 2:1. d Mixture of 2-iodo-1,2-
diphenylethanone (51%) and 18 (20%).
to be exclusive and 1-(2,4-dimethoxy-phenyl)-2-iodo-ethanone
10b, 1-(2,6-dimethoxy-phenyl)-2-iodo-ethanone 10c, 1-(3,5-
dimethoxy-phenyl)-2-iodo-ethanone 10d, 1-(2,4,6-trimethoxy-
phenyl)-2-iodo-ethanone 10e or 2-iodo-6-methoxy-3,4-dihydro-
2H-naphthalen-1-one 12 were quantitatively formed and
isolated in excellent yields. In these cases the reactivity of the
aerobic oxidative iodination process was also higher in the
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micelle-based aqueous system than under “on water” reaction
conditions. We further checked the selectivity of iodination on
1-(4-methoxyphenyl)propan-2-on 13 (entry 9) which possesses
three potential positions for electrophilic derivatisation: the
activated aromatic ring and two a-to carbonyl positions on the
benzylic and methyl carbon atoms and established that exclusive
functionalization of the benzylic position took place, giving the
isolated product 1-hydroxy-1-(4-methoxyphenyl)propan-2-on
14. The 1-iodo-1-phenyl-propan-2-ones are known as less stable
compounds which could be stabilized with nucleophilic solvents
like MeOH or H2O to form 1-methoxy or 1-hydroxy-1-phenyl-
propan-2-ones.23 Regioselective a-hydroxylation of the benzylic
position was also observed in the case of 1,1-diphenylpropan-
2-one 15 (entry 10) and 1,3-diphenylpropan-2-one 17 (entry 11)
where by using the I2/air/NaNO2(cat.)/H2SO4 system in the
SDS aqueous micelle medium 1,1-diphenyl-1-hydroxypropan-2-
one 16 or 1,3-diphenyl-1-hydroxypropan-2-one 18 were formed.
The primary formation of iodinated product was proved in the
case of the reaction of 17 on water, where a mixture of 1-iodo and
1-hydroxy derivatives was isolated. These findings could open an
efficient method for selective hydroxylation of benzyl ketones.
We finally tested the method on 3-oxo-3-phenyl-propionic acid
ethyl ester 19 (entry 12) as a model 1,3-dicarbonyl compound
and the formation of 2-iodo-3-oxo-3-phenyl-propionic acid ethyl
ester 20 in high yield was observed in SDS aqueous micellar
medium, while only a moderate yield of the transformation
was found under “on water” reaction conditions. Isolation
of products from the crude reaction mixtures obtained after
the mmol scale reactions described in Table 3 was performed
by extraction with tert-butyl methyl ether, while after larger
scale experiments isolation without using organic solvents was
applied.
these cases, since the use of non-dried MeCN or adding a
drop of water to the reaction system diminshed the ring/side
chain regioselectivity considerably in favour of side chain
iododerivatisation.
Conclusions
In conclusion, we successfully developed the efficient and
selective oxidative iodination of ketones in aqueous media using
molecular iodine, air as the terminal oxidant, NaNO2 as catalyst,
and H2SO4 as an activator of the overall catalytic process which
enables maximum iodine atom economy. To the best of our
knowledge, this is a first example of non-enzymatic aerobic
oxidative halogenation of organic molecules in water and it was
shown that the high efficiency of the catalytic aerobic process was
significantly accelerated in the micelle-based aqueous system.
The inexpensive anionic amphiphile sodium dodecyl sulfate
(SDS) was found to be an excellent promoter of aerobic a-iodo-
functionalization of a series of substituted ketones, while regios-
elective a-hydroxylation of benzyl-alkyl ketones was achieved.
In the SDS micelle-based aqueous system, regiospecific side
chain iodination of methoxy substituted aryl methyl ketones
to iodomethyl-aryl ketones was established, while ring iodo-
functionalization forming aryliodides was achieved in anhy-
drous MeCN. The use of water as a reaction medium and the
methodology of “micellar catalysis”27 for aerobic oxidative iodi-
nation of ketones with the I2/air/NaNO2(cat.)/H2SO4 reaction
system made the investigated method attractive and interesting
from both the economic and environmental points of view.
Experimental
The results in Table 3 illustrate that SDS aqueous micelle
works as an excellent medium for side chain regiselective
aerobic oxidative iodination of aryl methyl ketone. On the
other hand, there still remains the question of regioselec-
tive ring functionalization of aryl methyl ketones with the
I2/air/NaNO2(cat.)/H2SO4 reagent system, since the reaction
conditions during iodination of ketones favour a higher degree
of enolization of the ketone and consequently a-iodination,
even in the case of aprotic solvent MeCN. In the case of
F-TEDA-BF4 mediated fluorination24 or oxidative iodination,25
this switches the regioselectivity towards aromatic ring func-
tionalization. We thus had some doubts that solvent- directed
regioselectivity of iodination could be achieved when the
I2/air/NaNO2(cat.)/H2SO4 reagent system is used. When using
freshly distilled and dried MeCN as the reaction medium, we
finally succeeded in switching from side chain to aryl ring
regioselectivity of the reaction. In dry MeCN at 30 ◦C 1-(3-iodo-
2,6-dimethoxy-phenyl)-ethanone 21 was formed, with excellent
regioselectivity (95%; 5% of 10c was also formed) and eficiency
(73% of pure product) of the process when 9c was treated with
iodinating system Similarly, 1-(3,5-dimethoxy-phenyl)-ethanone
10d and 1-(2,4,6-trimethoxy-phenyl)-ethanone 10e were trans-
formed in anhydrous MeCN to 1-(2,6-diiodo-3,5-dimethoxy-
phenyl)-ethanone 22 (75% of pure product) or 1-(3-iodo-2,4,6-
trimethoxy-phenyl)-ethanone 23 (74% of pure product), also in
these cases with high selectivity26 and efficiency. Minimization
of the presence of water was found to be very important in
Aerobic oxidative iodination of ketones in a micelle-based
aqueous system. General procedure
Ketone (1 mmol) was placed in a two necked glass flask (50 mL,
one neck closed with a rubber septum) equipped with a magnetic
stirrer bar, 4 mL of water, SDS (144 mg, 0.5 mmol) and 96%
sulfuric acid (47 mg, 0.5 mmol) were added and stirred for a few
minutes. Afterwards fine powdered molecular iodine (127 mg,
0.5 mmol) was added to the reaction mixture, the open neck
was then closed with a rubber balloon (1 L) filled with air
and the stirred reaction flask heated to 60 ◦C. Sodium nitrite
(NaNO2) catalyst (8.28 mg, 0.12 mmol) dissolved in water (1 mL)
was introduced through the septum into the reaction mixture
in 3 portions (0.04 mmol, 2.76 mg of catalyst) at intervals of
1/4 reaction time and the reaction system stirred (500–700 rpm)
at 60 ◦C until the reaction mixture lost the iodine colour (see
Table 3). The reaction mixture was cooled to r.t., diluted with
tert-butyl methyl ether (20 mL) and the ether phase without
shaking separated from the water phase. Then the water phase
was gently extracted with tert-butyl methyl ether (10 ml) and
the combined ether phases were first discolored by adding a few
drops of 40% aqueous solution of Na2SO3, neutralized with a few
drops of saturated aqueous NaHCO3 and dried over anhydrous
Na2SO4. After removal of the solvent under reduced pressure,
the crude products obtained were purified by column or TLC
preparative chromatography (SiO2, CH2Cl2:n-hexane 9:1) and
identified by NMR and MS analysis. Spectroscopic data and
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references for known compounds 2, 4, 6, 8, 10a-c, 12, and 20 are
presented in the ESI.†
drops of 40% aqueous Na2SO3, neutralized with a few drops of
saturated aqueous NaHCO3 and dried over anhydrous Na2SO4.
The solvent was removed under reduced pressure, the crude
products obtained were identified from their spectroscopic data
and purified using column chromatography (SiO2, CH2Cl2:n-
hexane 9.5:0.5). Spectroscopic data and the reference for known
compound 21 are presented in the ESI.†
1-(3,5-Dimethoxyphenyl)-2-iodoethanone
(10d). column
chromatography (SiO2, CH2Cl2/n-hexane 9.5:0.5); 245 mg
(80%); white crystals (from n-hexane); mp(57–59 ◦C); 1H
NMR: d = 3.84(s, 6H), 4.33(s, 2H), 6.67(t, J = 2.3 Hz, 1H),
7.11(d, J = 2.3 Hz, 2H); 13C NMR: d = 1.6(CH2I), 55.6(CH3),
106.0(CH), 106.7(CH), 135.2(C), 160.9(C), 192.5(CO); IR:
n(cm-1) = 1675, 1611, 1593, 1468, 1431, 1355, 1304, 1211,
1164, 1020, 750, 673, 613; MS: m/z: 306(M+, 100%), 165(100),
151(17), 137(8), 122(8), 77(10); HRMS: m/z calcd. for
C10H11O3I: 305.9761, found: 305.9752.
1-(2,6-Diiodo-3,5-dimethoxyphenyl)-ethanone (22). Prepar-
ative TLC chromatography (SiO2, CH2Cl2/n-hexane 9.5:0.5;
Rf = 0.65); 324 mg (75%); white crystals (from n-hexane);
mp(148–151 ◦C); 1H NMR: d = 2.63(s, 3H), 3.92(s, 6H), 6.38(s,
1H); 13C NMR: d = 29.0(CH3), 56.8(CH3), 70.4(C), 94.9(CH),
152.2(C), 159.6(C), 204.3(CO); IR: n(cm-1) = 1705, 1562, 1464,
1413, 1358, 1322, 1219, 1042, 974, 822; MS: m/z: 432(M+,
100%), 417(40), 374(10); HRMS: m/z calcd. for C10H10O3I2:
431.8728; found: 431.8719.
2-Iodo-1-(2,4,6-trimethoxyphenyl)-ethanone (10e). column
chromatography (SiO2, CH2Cl2/n-hexane 9.5:0.5); 285.5 mg
(85%); white crystals (from n-hexane); mp(89–91 ◦C); 1H NMR:
d = 3.81(s, 6H), 3.83(s, 3H), 4.29(s, 2H), 6.11(s, 2H); 13C NMR:
d = 10.9(CH2I), 55.5(CH3), 56.0(CH3), 90.5(CH), 109.3(C),
159.2(C), 163.3(C), 194.0(CO); IR: n(cm-1) = 1671, 1606, 1588,
1458, 1411, 1335, 1255, 1207, 1161, 1129, 999, 811; MS:
m/z: 336(M+, 11%), 321(7), 195(100); HRMS: m/z calcd. for
C11H13O4I: 335.9868, found: 335.9858.
1-(3-Iodo-2,4,6-trimethoxyphenyl)-ethanone (23). column
chromatography (SiO2, CH2Cl2/n-hexane 9.5:0.5); 248.5 mg
(74%); white crystals (from n-hexane); mp(94–95 ◦C); 1H
NMR: d = 2.49(s, 3H), 3.79(s, 3H), 3.85(s, 3H), 3.91(s, 3H),
6.28(s, 1H); 13C NMR: d = 32.3(CH3), 56.1(CH3), 56.7(CH3),
62.9(CH3), 73.5(C), 91.9(CH), 119.6(C), 158.0(C), 158.6(C),
160.5(C), 201.0(CO); IR: n(cm-1) = 1687, 1585, 1382, 1324,
1242, 1210, 1105, 1011, 915, 810; MS: m/z: 336(M+, 50%),
321(100), 306(20), 263(6); HRMS: m/z calcd. for C11H13O4I:
335.9866, found: 335.9859.
1-Hydroxy-1-(4-methoxy-phenyl)-propan-2-one23 (14). pre-
parative TLC (SiO2; CH2Cl2/EtOH = 9.5:0.5); 144 mg (80%);
oily product; 1H NMR: d = 2.06(s, 3H), 3.81(s, 3H), 4.25(d, J =
4.7 Hz, 1H), 5.04(d, J = 4.7 Hz, 1H), 6.90(d, J = 8.7 Hz,
2H), 7.22(d, J = 8.7 Hz, 2H); 13C NMR: d = 25.1, 55.2,
79.5, 114.3, 128.5, 129.9, 159.8, 207.3; MS: m/z: 180(M+, 2%),
163(15), 137(100), 109(18), 94(21), 77(24); HRMS: m/z calcd.
for C10H12O3: 180.0786, found: 180.0781.
Notes and references
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1-Hydroxy-1,1-diphenyl-propan-2-one28
(16). preparative
TLC (SiO2; CH2Cl2/EtOH = 9.5:0.5); 185 mg (82%); mp(63.0–
65.0 ◦C); 1H NMR: d = 2.27(s, 3H), 4.85(broad s, 1H), 7.37(m,
10H); 13C NMR: d = 26.2, 85.7, 128.1, 128.2, 128.5, 141.3,
208.6; MS: m/z: 183(M+-MeCO, 36%), 105(100), 77(11).
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2-Hydroxy-1,2-diphenyl-ethanone29 (18). preparative TLC
(SiO2; CH2Cl2/EtOH = 9.5:0.5); 176 mg (83%); mp(135.5–
137.0 ◦C); 1H NMR: d = 4.57(d, J = 6 Hz, 1H), 5.95(d, J = 6 Hz,
1H), 7.25–7.50(m, 8H), 7.91(d, J = 9 Hz, 2H); 13C NMR:
d = 76.2, 127.7, 128,5, 128.7, 129.1, 129.2, 133.9, 139.0, 198.9;
MS: m/z: 212(M+, 1%), 108(63), 105(100), 79(60), 77(92);
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Aerobic oxidative ring iodofunctionalization of aryl methyl
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