Selective synthetic routes to sterically hindered unsymmetrical diaryl ketones via arylstannanes

Article abstract of DOI:10.1021/jo102366q

Bulky arylstannanes and bulky aroyl chlorides are good reaction partners for the synthesis of two-, three-, and even four-ortho-substituted benzophenones, in good to excellent isolated yields (47-91%). Three simple and direct routes, with differential advantages, are proposed: (i) a catalyst-free protocol, in o-dichlorobenzene (ODCB) at 180 °C; (ii) a room temperature protocol, using AlCl₃ (0.5 equiv), in dichloromethane (DCM); and (iii) a solvent-free, indium-promoted procedure. A radical mechanism is proposed for the indium-mediated reactions.2011 American Chemical Society.

Full text of DOI:10.1021/jo102366q

ARTICLE
pubs.acs.org/joc
Selective Synthetic Routes to Sterically Hindered Unsymmetrical
Diaryl Ketones via Arylstannanes
Marcos J. Lo Fiego, Gustavo F. Silbestri, Alicia B. Chopa,§ and María T. Lockhart*
Instituto de Química del Sur (CONICET - UNS), Departamento de Química, Universidad Nacional del Sur, Avenida Alem 1253, Bahía
Blanca, B8000CPB, Argentina
S Supporting Information
b
ABSTRACT: Bulky arylstannanes and bulky aroyl chlorides are
good reaction partners for the synthesis of two-, three-, and even
four-ortho-substituted benzophenones, in good to excellent iso-
lated yields (47-91%). Three simple and direct routes, with
differential advantages, are proposed: (i) a catalyst-free protocol,
in o-dichlorobenzene (ODCB) at 180 °C; (ii) a room temperature
protocol, using AlCl3 (0.5 equiv), in dichloromethane (DCM);
and (iii) a solvent-free, indium-promoted procedure. A radical
mechanism is proposed for the indium-mediated reactions.
Chart 1
’ INTRODUCTION
Benzophenones are common structures found in organic
materials as well as in natural products and pharmaceutical
compounds. Most of the biologically active benzophenones are
sterically crowded substrates possessing, at least, substituents on
both ortho positions to the ketone moiety.1 These compounds
are not readily accessible by conventional routes. Thus, electro-
philic aromatic substitution (EAS) such as Friedel-Crafts (F-
C) acylation2 and cross-coupling reactions of acyl chlorides with
organometallic reagents3 are efficient and preferred methods to
form ketones in good yields, but they are generally limited to the
synthesis of noncrowded ketones. These congested substrates
could be synthesized through the addition of aryllithium or
arylmagnesium to aldehydes followed by oxidation of the corre-
sponding carbinols.4 Most recently, there have been proposed two
more gentle additional protocols: rhodium-catalyzed oxidative
arylation of aldehydes5 and carbonylative Suzuki-Miyaura cou-
plings of aryl boronics with ortho-disubstituted aryl iodides.6 In the
last years we have been involved in the synthesis of arylstannanes as
well as in their application as intermediates in organic synthesis;7
recently, we have developed new procedures for the regiospecific8
catalyst-free mono-, bi-, and triaroylation of aromatic rings based on
the exceptional leaving group ability of the trialkylstannyl group in
EAS.9 Taking into account our experience and that the proposal of
new routes for the synthesis of severely hindered benzophenones
would be highly desirable, we considered it interesting to explore
the application of the reaction of arylstannanes with aroyl chlorides
to the synthesis of these especial ketones. Herein, we are gratified to
report the synthetic potential of this pair of reagents, under three
different protocols, as well as the special workup carried out in order
to recover the trialkyltin chlorides generated (see the Experimental
Section).
’ RESULTS AND DISCUSSION
Reactions in o-Dichlorobenzene (ODCB). We prepared a
representative series of arylstannanes carrying either one or two
substituents attached to the ortho positions of the aromatic ring
(1a-d)10 and we studied their reaction toward different com-
mercially available ortho-substituted aroyl chlorides (2a-e)
(Chart 1) under the optimized reaction conditions we have
previously established, that is, in ODCB as solvent, at 180 °C.9b
The results obtained are summarized in Table 1.
First, we carried out a series of reactions between 1-naphthoyl
chloride (2a), carrying only one ortho substituent, and different
stannanes (1a-d) with increasing steric requests; pleasantly, we
noticed that all reactions occurred through the ipso-substitution
Received: November 29, 2010
Published: February 22, 2011
r
2011 American Chemical Society
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Table 1. Reactions of Arylstannanes with Aroyl Chlorides in ODCB
a All reactions were conducted in 1.0 M Ar1SnR3 with 1.2 equiv of Ar2COCl at 180 °C (oil bath). b Determined by GC (using tetradecane as internal
standard). Isolated yields from 1.0 mmol scale experiments (column chromatography) are given in parentheses. c Together with 4bb (35%). d Together
with 4bc (25%).
of the stannyl group providing the expected ketones in good to
excellent isolated yields (61% to 85%, entries 1 to 4) in rather
short times (2 to 5 h).
Much to our regret, the reaction of 1b with 2b gave a mixture
of isomeric ketones, i.e., (2,6-dimethoxyphenyl)(2-methoxyphe-
nyl)methanone (3bb) and (2,6-dimethoxyphenyl)(4-methoxy-
phenyl)methanone (4bb) (1:2 ratio), generated by acylde-
stannylation and direct acylation-protodestannylation of the
ring, respectively (entry 6). Similarly, the reaction of 1b and 2c
afforded a mixture of (2,4,6-trimethylphenyl)(2-methoxyphe-
nyl)methanone (3bc) and (2,4,6-trimethylphenyl)(4-methoxy-
phenyl)methanone (4bc) in a 1.25:1 ratio (entry 10).11 So, we
set out to investigate the reaction of 1b and 2b with the aim of
finding the most suitable conditions for reducing the competing
non-ipso-substitution (Table 2).
To explore the synthetic potential of this approach to the access
to sterically hindered benzophenones we carried out a series of
reactions between the arylstannanes and different mono- or di-
ortho-substituted aroyl chlorides (2b-e) (Table 1). With only two
exceptions, the reactions were regiospecific affording the desired
ketones in good yields (53% to 71%). Moreover, experiments 12 to
16 confirm that it is possible to synthesize heterocyclic benzophe-
nones as well as benzophenones bearing electron-attracting groups
such as fluorine in both ortho positions.
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Table 2. Optimization of the Acyldestannylation Reaction of
1b with 2b in ODCB
Table 3. Optimization of Conditions for the AlCl3-Catalyzed
Reaction of 1d with 2b
products (%)b
products (%)a
entrya
temp (°C)
time (h)
3db
4db
3db:4db
entry 1b [M] temp (°C) time (h)
3bb
4bb
3bb:4bb
1
2
-10
0
4
4
17
19
30
49
25
58
60
78
-
-
-
-
25
-
20
-
1
2
3
4
1.00
0.66
1.00
0.66
180
180
130
130
2
6
17
52
43
60
35
8
1:2
6.7:1
5:1
3
10
4
9
9
4
RT
40
4
12
10
6:1
a Determined by GC (using tetradecane as internal standard).
5
4
1:1
3:1
6
RT
RT
RT
6
We first studied the effect of dilution. The GC analysis of the
isomer compositions showed that an increment of dilution
produced an increase of ketone 3bb over 4bb (6.7:1 ratio)
(Table 2, entry 2); unfortunately, we were not able to obtain
an isomerically pure product.12 On the other hand, considering
the outstanding leaving group ability of the trialkylstannyl group,
we supposed that under lower reaction temperatures, acyldes-
tannylation would be more competitive over direct acylation, so,
we carried out a series of reactions at lower temperatures. Once
more, we obtained a mixture of ketones although with a sensible
increment of the amount of 3bb over 4bb (5:1 ratio) (Table 2,
entry 3).13 Taking into account these results we carried out an
experiment working both at 130 °C and at lower concentration,
but a similar result was obtained (Table 2, entry 4). Thus, it was
not possible to avoid the unwanted direct acylation of the ring,
with dilution being the most appropriate condition to decrease it
although longer reaction time (6 h) was required for completion.
Under the optimized conditions the reaction of 1b with 2c gave
also a mixture of 3bc and 4bc in a 3:1 ratio (eq 1).
7
8c
14
14
a All reactions were conducted in DCM at 0.10 M concentration of
Ar1SnR3, using 1.2 equiv of Ar2COCl in the presence of 1.2 equiv of
AlCl3 unless otherwise stated. b Determined by GC (using tetradecane as
internal standard). c Performed in the presence of 0.5 equiv of AlCl3
performed with arylstannanes.15 Looking for alternative reaction
conditions for the synthesis of crowded benzophenones, we
search the best conditions for the selective reaction of bulky
arylstannanes with bulky aroyl chlorides using AlCl3 as catalyst in
dichloromethane (DCM) as solvent.
First, we optimized conditions for the reaction of 1d with 2b,
which would give the most crowded ketone 3db. The results are
shown in Table 3.
It was clear that temperature rise (from -10 to 40 °C)
produced an increase of the yields (Table 3, entries 1-5);
nevertheless, at 40 °C the selectivity fails and both isomeric
ketones, 3db and 4db, were detected in a 1:1 ratio (GC/MS).
Therefore, we worked at room temperature. Experiments 6 and
7, carried out with the main goal of determining the optimal
reaction time, showed that although yields increased with time,
unexpectedly, after 14 h, a mixture of ketones 3db and 4db (3:1)
was obtained. Could it be possible to assume that the presence of
4db is related to the reversibility of the reaction? It is known that
F-C acylations are virtually irreversible.2 Nevertheless, when the
resonance stabilization is reduced because the acyl group is tilted
out of the plane of the aromatic nucleus by neighboring bulky
substituents, as in our case, the pattern of irreversibility of F-C
acylation may be confronted.16 To prove our hypothesis, a
mixture of 3db, AlCl3, and Me3SnCl, 1:1:1,17 was stirred at room
temperature. After 14 h, the GC/MS of the crude product
effectively showed a mixture of 3db and 4db (2.3:1), confirming
the reversibility of the reaction. On the other hand, a mixture of
3db, AlCl3, and Me3SnCl, 1:1:1, was stirred at 40 °C for 4 h; only
traces of 4db were detected in the crude product indicating that
the results obtained in experiment 5 were due to the effective
competition of the direct acylation of the ring under those
conditions.
Taking into account the results obtained in the reactions
performed between 1b and different aroyl chlorides, it is prob-
able that the mixtures of isomeric ketones obtained in experi-
ments 6 and 10 (Table 1) are the result of an improvement of the
competitiveness of the direct acylation reaction due to steric
requirements (ketones 3bb and 3bc supported three bulky
groups in the ortho-position). On the other hand, experiments
2, 12, and 15 (Table 1) proceed with total selectivity (ketones
3ba and 3bd supported only two ortho-groups and in ketone 3be
steric requirements of fluor are small).14
On the basis of the results obtained, we can say that the
reaction of bulky arylstannanes with bulky aroyl chlorides in
ODCB, at 180 °C, is, in general, adequate for the catalyst-free
regioselective synthesis of bi-, tri-, and even tetra-ortho-substi-
tuted benzophenones in reasonable yields.
The results obtained show that the percentage of ketone 4db
increases with reaction time and temperature. This could be
explained by considering that the generation of ketone 3db is a
AlCl3-Catalyzed Reactions. Neumann has reported that
AlCl3 is an effective catalyst in diverse substitution reactions
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Table 4. Optimization of the AlCl3-Catalyzed Acyldestanny-
lation Reaction of 1b with 2b
On the basis of the results obtained we can say that AlCl3 is an
effective catalyst for the synthesis of these highly hindered
benzophenones, through the reaction of bulky aroyl chlorides
with bulky arylstannanes, at room temperature. Moreover, it is
almost possible to compensate the steric hindrance and the para-
directing effect of the OMe group. However, one disadvantage is
that, although we used a deficiency of catalyst, it cannot be
recovered after aqueous workup and a considerable amount of
toxic waste is generated.
Indium-Mediated Reactions. In the last years, indium-
mediated reactions have expanded in the literature due to the
special properties of indium metal.19 Thus, it is unaffected by air,
moisture, or oxygen at ambient temperature and, most impor-
tantly, the element itself is without any apparent toxicity. On the
basis of the fact that In(0) acts as a Lewis acid catalyst in aromatic
F-C reactions,19 we considered it interesting to examine the
possibility of promoting acyldestannylation reactions by means
of In(0) as catalyst instead of AlCl3.
products (%)b
entrya
temp (°C)
3bb
4bb
3bb:4bb
1
0
43
40
40
29
20
27
2.0
1.5:1
2:1
2
RT
40
RT
3
4c
1.5:1
10:1
56 (47)
a All reactions were conducted in 0.10 M Ar1SnR3 with 1.2 equiv of
Ar2COCl in the presence of 0.5 equiv of AlCl3 unless otherwise stated.
b Determined by GC (using tetradecane as internal standard). Isolated
yield from 1.0 mmol scale experiment (column chromatography) is
given in parentheses. c Performed in 0.05 M Ar1SnR3
First, a mixture of arylstannane 1a, aroyl chloride 2a, and In(0)
(1:1.2:1) in DCM as solvent was stirred at room temperature.
After 8 h no starting material was detected by TLC and the GC/
MS analysis of crude showed the presence of low amounts of
ketone together with a large amount of toluene, that is, proto-
destannylation product. Second, we performed the same reaction
but employing R,R,R-trifluortoluene instead of DCM. Once
more, only traces of ketone were detected and toluene was the
main product. Finally, we decided to carry out the reaction in the
absence of solvent. In the course of time the reaction mixture
became quite viscous and after 13 h the stirring was not possible.
Anyway, the GC/MS analysis of the mixture showed the
presence of ketone together with starting material and only
traces of toluene. To achieve an efficient stirring throughout the
reaction time we carried out a reaction at 60 °C (oil bath). The
starting material was consumed after 7 h as shown by TLC.
Purification by column chromatography (from independent
experiments) gave the desired ketone 3aa, identified by NMR,
in 78% yield (Table 5, entry 1). It is important to note that a
control experiment showed that no reaction occurred in the
absence of In(0), indicating that the metal acts as a promoter of
the reaction. These results encouraged us and we carried out a
series of representative experiments which are summarized in
Table 5.
It should be mentioned that each reaction was performed at
the lowest temperature, which allowed keeping the stirring of the
reaction mixture during reaction time. An analysis of the results
summarized in Table 5 shows that the indium-mediated selective
synthesis of hindered benzophenones 3aa, 3ca, 3da, 3ab, 3cb,
3db, 3ac, and 3dc in good to excellent isolated yields (49 to 91%)
is possible. Moreover, an increase in reaction temperature causes
a sharp reduction of reaction time without affecting the yield
(entry 9 vs 10). More significantly, use of substoichiometric
amounts (0.2 equiv) of In(0) does not have a major detrimental
effect on the yield (entry 7). Unfortunately, the results obtained
with the more electrophilic acid chlorides 2d and 2e were
unsuccessful. At room temperature, the reactions of 1d with 2d
and 2e were negative even after long reaction times (entries 11
and 14). The same reactions performed at higher temperature
(60 °C) provided the expected ketone but the major products
were those derived from the unwanted direct acylation, i.e., 4dd
and 4de, respectively (entries 12 and 15). Moreover, stannane
1a did not react with 2e even after 52 h at 60 °C (entry 13).
These unexpected reaction outcomes, in spite of the high
kinetically controlled process, while the formation of isomer 4db
is the result of low stannyldeacylation of 3db and the major
thermodynamic stability of isomer 4db.
To minimize the inconvenience caused by the reversibility of
the reaction we analyzed the effect of using minor amounts of
AlCl3 as catalyst and, pleasantly, we found that 0.5 equiv of AlCl3
was enough for the synthesis of 3db (14 h), at room temperature,
in 78% yield (entry 8). Probably, the Me3SnCl produced during
the reaction may also work as a weak Lewis acid.18
The optimized conditions were applied to the reaction of 1d
with 2c, which afforded isomerically pure ketone 3dc in high
isolated yield (eq 2).
Our next goal was to find optimal reaction conditions to
overcompensate the high para-directing force of the OMe group
which had inhibited the selective synthesis of both 3bb and 3bc
in ODCB (Table 1). With this purpose we carried out a series of
reactions between 1b and 2b (Table 4). Experiments 1 to 3 are
representative of the influence of temperature, showing that
there are no relevant changes either in the yield or in the isomer
mixtures obtained, working from 0 to 40 °C.
On the other hand, experiment 4 showed that dilution
produced a pronounced increment in the selectivity of the
reaction providing a mixture of 3bb and 4bb in a 10:1 ratio.12
The same conditions applied to the reaction of 1b with 2c
providing 82% of a mixture of 3bc and 4bc in a 20:1 ratio (eq 3).
It is noteworthy that the high selectivity achieved allowed us to
isolate isomerically pure ketones 3bb and 3bc in 47% and 73%
yield, respectively.
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Table 5. Indium-Mediated Reactions of Arylstannanes with
Aroyl Chlorides
Table 6. Indium-Mediated Reactions of 1b with Aroyl
Chlorides
entrya Ar1SnR3 Ar2COCl temp (°C) time (h) Ar1COAr2 yieldb (%)
1
2
3
4
5
6
7c
8
9
1a
1c
1d
1a
1c
1d
1d
1a
1d
1d
1d
1d
1a
1d
1d
2a
2a
2a
2b
2b
2b
2b
2c
2c
2c
2d
2d
2e
2e
2e
60
7
2
3aa
3ca
3da
3ab
3cb
3db
3db
3ac
3dc
3dc
3dd
3dd
3ae
3de
3de
82 (78)
95 (91)
67 (64)
52 (49)
83 (80)
55 (52)
49
entrya
Ar2COCl
temp (°C)
time (h)
products, yield (%)b
60
60
2
1
2
3c
4d
5
2a
2b
2b
2b
2c
2c
2c
60
80
80
80
RT
0
4
4
5
3
4
2
2
3ba, 26
3bb, 29
3bb, 3
4ba, 52
4bb, 41
4bb, 29
4bb, 42
4bc, 33
4bc, 43
4bc, 26
100
80
1
2
80
2
3bb, 30
3bc, 16
3bc, 14
3bc, 19
80
2
RT
RT
60
27
25
3
70 (67)
58 (54)
66 (62)
6
7
80
10
a All reactions were conducted in solvenless conditions using 1.0 equiv of
Ar1SnR3, 1.2 equiv of Ar2COCl and 1.0 equiv of indium metal, unless
otherwise stated. b Determined by GC (using tetradecane as internal
standard). c Performed with 0.5 equiv of indium metal. d Performed with
2.0 equiv of indium metal
d
11
12
13
14
15
RT
60
14
3
-
32e
d
60
52
55
13
-
d
RT
60
-
15f
a All reactions were conducted in solvenless conditions with 1.0 equiv of
Ar1SnR3, 1.2 equiv of Ar2COCl, and 1.0 equiv of indium metal, unless
otherwise stated. b Determined by GC (using tetradecane as internal
standard). Isolated yields from 1.0 mmol scale experiment (column
chromatography) are given in parentheses. c Performed with 0.2 equiv of
indium metal. d Starting material was almost completely recovered.
e Together with 32% of 4dd. f Together with 30% of 4de.
Scheme 1. Proposed Mechanistic Pathways for the Indium-
Mediated Homolytic Aromatic ipso-Substitution of Aryltins
electrophilicity of 2d and 2e, led us to suppose that these
reactions promoted by indium did not go through a conventional
electrophilic attack. So, we it considered interesting to investigate
whether this procedure could be suitable for the ipso-aroylation
of reluctant compound 1b. The results obtained are displayed
in Table 6.
It can be seen that whatever the aroyl chloride employed, even
using a deficiency or an excess of In(0) (experiments 3 and 4) or
working at different temperatures (entries 5 to 7) it was not
possible to overcome the strong para-directing effect of the OMe
group. These reactions led to a mixture of the expected ketone
together with that generated by direct acylation of the ring. It
should be mentioned that in experiment 6, carried out at 0 °C,
the presence of the direct acylation product supporting the
tributyltin group, i.e., mesityl(3-(tributylstannyl)-4-methoxyphe-
nyl)methanone was detected (GC/MS), indicating that this
ketone acts as an intermediate in the generation of 4bc. It should
be mentioned that, once more, reactions performed with 2e were
negative even at 60 °C recovering starting materials.
It is known that, because of its low first ionization potential,
In(0) is capable of promoting single-electron transfer (SET)
processes.19 To prove whether acyldestannylations proceeded
through a polar or a free radical pathway, we performed the
reaction of 1d and 2b in the presence of 0.5 equiv of di-tert-
butylnitroxide (DTBN) as radical scavenger. Compared with a
blank reaction, we noticed that the addition of DTBN had a
dramatic retardation effect and only traces of ketone were
detected recovering the starting substrate.
with generation of an acyl radical and In(I) chloride salt. The acyl
radical thus formed reacts with the arylstannane through a
homolytic ipso aromatic substitution affording the ketone. The
selective ipso-substitution is a consequence of the enhanced
hyperconjugation of the unpaired electron with the β-carbon-
tin bond, namely, the β-effect.20 The tin radical should be rapidly
lost and reacts with the aroyl chloride, regenerating an acyl
radical (Scheme 1). Thus, In(0) acts as an initiator of the radical
process. This is supported by the fact that 0.2 equiv of In(0) is
enough to promote the acyldestannylation reaction.
’ CONCLUSIONS
Our results enable us to affirm that bulky arylstannanes and
bulky aroyl chlorides are good reaction partners for the synthesis
of two-, three-, and even four-ortho-substituted benzophenones,
in good to excellent yields. We proposed three different proce-
dures which broaden the applicability of these transformations.
On the basis of these results, we believe that the reaction
proceeds initially through a SET from In(0) to the aroyl chloride
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Initially, we have demonstrated the effectiveness of the
catalyst-free reaction of these reagents carried out in ODCB, at
180 °C. Thus, highly hindered benzophenones were regiospeci-
fically synthesized in good yields (53 to 85%) in generally short
times. Nevertheless, the high leaving group ability of tin was not
enough to overcompensate the steric bulk and the para-directing
effect of the OMe group in the synthesis of 3bb and 3bc from 1b.
This drawback could be reversed working in DCM, using
AlCl3 as catalyst. Thus, we have been able to find optimal
reaction conditions not only for the synthesis of highly hindered
benzophenones but also for the highly selective synthesis of
ketones 3bb and 3bc. It is important to mention that these
reactions were carried with a substoichiometric amount of
catalyst (0.5 equiv) and at room temperature.
Finally, we have established that In metal acts as a promoter in
these reactions and that even substoichiometric amounts (0.2
equiv) of In(0) are enough to promote them. The ketones are
synthesized in good to excellent yields (49-91%) at relatively
low temperatures and in the absence of solvent. Unfortunately,
these conditions were not suitable for the regiospecific aroylation
of the o-methoxy-substituted aryltin 1b; furthermore, highly
electrophilic acid chlorides like 2d and 2e give a mixture of the
desired ketones together with important amounts of the un-
wanted direct acylation products. As far as we know, these are the
first reported examples of In(0)-catalyzed-reactions connected
with substitution reactions on organostannanes. We believe that
these reactions proceed through a SET process. A detailed
investigation on the mechanism and on the scope and limitations
of this method for the synthesis of carbonyl compounds via
organostannanes is currently in progress in our laboratory.
(2-Isopropil-4-methoxy-5-methylphenyl)trimethylstan-
nane (1c).. Colorless liquid: 1H NMR (300 MHz, CDCl3) δ (ppm)
7.25 (s, 1H), 6.78 (s, 1H), 3.86 (s, 3H), 3.32 (m, 1H), 2.45 (s, 3H), 1.27
(d, J = 6.8 Hz, 6H), 0.31 (s, 2JHSn = 26 Hz, 9H); 13C NMR (75.5 MHz)
δ (ppm) 157.5, 143.1, 133.5, 133.2, 131.6, 111.8, 55.2, 26.8, 24.6,
22.7, -8.7 (1JCSn = 165/173 Hz); MS (EI, 70 eV) m/z (% rel intensity,
ion) 328 (4, Mþ), 313 [60, (Mþ - Me), Sn pattern], 298 [100, (Mþ
-
2Me), Sn pattern], 297 [17, (Mþ - OMe), Sn pattern], 283 [40, (Mþ -
3Me), Sn pattern]. Anal. Calcd for C14H24OSn: C, 51.41; H, 7.40.
Found: C, 51.55; H, 7.38.
The experimental procedure employed in the reactions carried out in
ODCB has been reported in our previous paper.9b
Representative Procedure for AlCl3-Catalyzed Reactions:
Synthesis of (2,6-Dimethylphenyl)(2,4,6-trimethylphenyl)-
methanone (3dc; eq 2).5 To a flame-dried two-necked round-
bottomed flask loaded with AlCl3 (0.056 g, 0.5 mmol) and dry DCM
(5 mL) was added 1.2 mmol (0.220 g) of 2,4,6-trimethylbenzoyl
chloride (2c) under an atmosphere of nitrogen. The mixture was stirred
until the suspension had fully dissolved and then was added via syringe to
a stirred solution of 1.0 mmol (0.270 g) of (2,6-dimethylphenyl)tri-
methylstannane (1d) in 5 mL of dry DCM contained in a septum-sealed
round-bottomed flask. The system (immersed in a cooling bath of liquid
nitrogen) was purged with nitrogen by means of three pump-fill cycles.
After addition of 10 μL of tetradecane (internal standard) the reaction
mixture was stirred at room temperature for 6 h and then hydrolyzed by
adding it to ice (5 g). The aqueous phase was extracted with DCM (3 ꢀ
5 mL) and the organic layers were washed with brine (5 mL). The
resulting aqueous solution was reserved for further treatment described
below. The combined organic layers were dried over Na2SO4, filtered,
analyzed by GC, and then concentrated in vacuo. The residue was
chromatographed on silica gel (60 Å, 70-230 mesh) eluting with
hexanes/DCM (90:10) to afford 0.207 g (82%) of 3dc as a white solid:
mp 77-79 °C; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.09 (t, J = 7.6
Hz,1H), 6.93 (d, J = 7.6 Hz, 2H), 6.76 (s, 2H), 2.20 (s, 3H), 2.07 (s, 6H),
2.04 (s, 6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 202.5, 141.3,
140.2, 138.0, 136.9, 136.3, 129.9, 129.8, 128.9, 21.1, 20.7, 20.6. (3dc is
also found in Table 1, entry 11.)
Representative Procedure for Indium-Mediated Reac-
tions: Synthesis of (2-methylphenyl)-1-naphthylmethanone
(3aa; Table 5, Entry 1).25. In a flame-dried Schlenk tube (fitted with a
Teflon plug valve) 1.2 mmol (0.230 g) of 1-naphtoyl chloride (2a) was
added to a stirred mixture of 1.0 mmol (0.382 g) of tributyl(2-methylphe-
nyl)stannane (1a) and indium powder (0.148 gr, 1.0 mmol) under a
nitrogen gas stream. After the purge procedure, the tube was capped and
the heterogeneous reaction mixture was stirred at 60 °C (oil bath) for 7 h.
After addition of a 10% (m/v) solution of NaOH (2 mL) and 10 μL of
tetradecane, the mixture was stirred at room temperature for 15 min and
then diluted with DCM (5 mL). The organic phase was successively
washed with water and brine, dried over Na2SO4, filtered, analyzed by GC,
and then concentrated in vacuo. Purification by column chromatography
on silica gel (60 Å, 70-230 mesh) doped with 10% of KF (hexanes/DCM
90:10) gave 0.189 g (77%) of 3aa as a white solid: mp 45-47 °C; 1H NMR
(300 MHz, CDCl3) δ (ppm) 8.73 (d, J = 8.1 Hz, 1H), 8.11 (d, J = 8.1 Hz,
1H), 8.03 (d, J = 7.4 Hz, 1H), 7.74-7.65 (m, 3H), 7.57-7.50 (m, 3H),
7.43 (d, J = 7.3 Hz, 1H), 7.32 (t, J = 7.3 Hz, 1H), 2.62 (s, 3H); 13C NMR
(75.5 MHz, CDCl3) δ (ppm) 200,1, 139.5, 138.1, 136.4, 133.8, 132.4,
131.3, 130.9, 130.3, 130.1, 128.4, 127.7, 126.4, 125.7, 125.3, 124.2, 20.5.
(3aa is also found in Table 1, entry 1.)
’ EXPERIMENTAL SECTION
General Experimental Methods. All reactions were carried out
under a dry nitrogen atmosphere. Acid chlorides were commercially
available and fractionally distilled under nitrogen before use except for
2,6-dimethoxybenzoyl chloride, which was recrystallized from hexane.
Aryltributylstannanes 1a and 1b were prepared by transmetalation of the
appropiate Grignard reagents with tributyltin chloride in anhydrous
THF. Aryltrimethylstannanes 1c and 1d were obtained from the
corresponding commercial aryl chlorides by photostimulated reaction
with Me3SnNa in liquid ammonia, according to the literature
procedures.21 Physical and spectroscopic characteristics of compounds
1a,22 1b,21 and 1d23 are consistent with those previously reported. For
unknown compound 1c evidence of identity and purity are shown
below. 1,2-Dichlorobenzene and dichloromethane were distilled from
calcium hydride under dry nitrogen atmosphere and stored over 4A
molecular sieves. Reactions were monitored by thin-layer chromatog-
raphy carried out on silica gel plates (60F-254) and visualized under UV
light or using 5% phosphomolybdic acid in ethanol. Column chroma-
tography was performed over silica gel 60 (70-230 mesh) doped with
10% of potassium fluoride.24 The NMR spectra were recorded on a 300
MHz spectrometer (300.1 MHz for 1H, 75.5 MHz for 13C). Chemical
shifts (δ) are reported in ppm downfield from tetramethylsilane, with
residual nondeuterated solvent resonance as internal reference (CDCl3:
δ 7.27 for 1H and δ 77.0 for 13C) and coupling constants (J) are in Hz.
Identity and purity of the products (crude or purified) were established
by using a GC/MS instrument (HP5-MS capillary column, 30 m ꢀ 0.25
mm ꢀ0.25 μm) equipped with a 5972 mass selective detector operating
at 70 eV (EI). Program: 50 °C for 2 min with an increase of 10 deg/min
to 280 °C. For gas-liquid chromatography (GLC) an instrument
equipped with a flame-ionization detector and a HP5 capillary column
(30 m ꢀ 0.25 mm ꢀ0.25 μm) was used.
(2,6-Dimethoxyphenyl)(2-methylphenyl)methanone (3ab;
Table 1, Entry 5 and Table 5, Entry 4). White solid: mp 115-
117 °C; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.37 (d, J = 7.7 Hz, 1H),
7.25 (m, 2H), 7.19 (t, J = 5.8 Hz, 1H), 7.06 (t, J = 7.4 Hz, 1H), 6.52 (d, J =
8.3 Hz, 2H), 3.62 (s, 6H), 2.59 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ
(ppm) 197.3, 157.5, 139.7, 137.6, 131.7, 131.6, 130.6, 125.4, 120.3, 104.2,
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ARTICLE
55.9, 21.5; MS (EI, 70 eV) m/z (% rel intensity, ion) 256 (1, Mþ), 241 [2,
(Mþ - Me)], 225 [100, (Mþ - OMe)]. Anal. Calcd for C16H16O3: C,
74.98; H, 6.29. Found: C, 75.26; H, 6.31.
(2-Methylphenyl)(2,4,6-trimethyl)methanone(3ac;Table1,
Entry 9 and Table 5, Entry 8).5. Pale yellow solid: mp 99-101 °C;
1H NMR (300 MHz, CDCl3) δ (ppm) 7.31-7.21 (m, 2H), 7.19 (d, J =
7.4 Hz, 1H), 7.04 (t, J = 7.4 Hz, 1H), 6.77 (s, 2H), 2.59 (s, 3H), 2.22 (s,
3H), 1.99 (s, 6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 202.5, 139.9,
138.5, 138.4, 137.1, 134.3, 132.2, 132.1, 131.8, 128.5, 125.8, 21.6, 21.1,
19.3.
(d, J = 8.0 Hz, 1H), 7.73 (d, J = 7.5 Hz, 1H), 7.45-7.35 (m, 3H), 7.29 (t, J=
7.6 Hz, 1H), 7.16 (s, 1H), 6.60 (s, 1H), 3.72 (s, 3H), 3.07 (m, 1H), 2.38 (s,
3H), 0.92 (d, J = 6.9 Hz, 6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
199.1, 159.2, 139.1, 138.0, 133.8, 131.4, 131.1, 131.0, 130.4, 130.3, 128.6,
128.3, 127.2, 126.2, 125.9, 124.3, 113.2, 55.3, 26.4, 22.3, 21.3; MS (EI, 70
eV) m/z (% rel intensity, ion) 318 (66, Mþ), 317 [50, (Mþ - H)], 303
[17, (Mþ - Me)], 275 [55, (Mþ - i-Pr)], 191 [25, (Mþ - Naph)], 127
(100). Anal. Calcd for C22H22O2: C, 82.99; H, 6.96. Found: C, 83.22;
H, 6.97.
(2-Isopropyl-4-methoxy-5-methylphenyl)(2,6-dimethoxy-
phenyl)methanone (3cb; Table 1, Entry 7 and Table 5, Entry
(2,6-Difluorophenyl)(2-methylphenyl)methanone (3ae;
Table 1, Entry 14). Pale yellow oil: H NMR (300 MHz, CDCl3)
1
1
5). White solid: mp 125-127 °C; H NMR (300 MHz, CDCl3) δ
(ppm) 7.61 (s, 1H), 7.55 (t, J = 8.3 Hz, 1H), 6.94 (s, 1H), 6.85 (d, J = 8.3
Hz, 2H), 4.11 (s, 3H), 3.95 (s, 6H), 3.43 (m, 1H), 2.93 (s, 3H), 1.31 (d,
J = 6.8 Hz, 6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 195.7, 159.4,
157.2, 140.3, 133.5, 131.2, 130.1, 129.5, 120.7, 113.6, 104.2, 55.9, 55.3,
26.4, 22.3, 22.2; MS (EI, 70 eV) m/z (% rel intensity, ion) 328 (2, Mþ),
313 [2, (Mþ - Me)], 297 [100, (Mþ - OMe)], 191 (9), 165 (44). Anal.
Calcd for C20H24O4: C, 73.15; H, 7.37. Found: C, 73.33; H, 7.39.
(2,6-Dimethylphenyl)-1-naphtylmethanone (3da; Table 1,
Entry 4 and Table 5, Entry 3). Pale yellow solid: mp 145-147 °C;
1H NMR (300 MHz, CDCl3) δ (ppm) 9.35 (d, J = 7.7 Hz, 1H), 8.11 (d,
J = 8.1 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.80 (t, J = 7.7 Hz, 1H), 7.73-
7.65 (m, 2H), 7.47 (t, J = 7.7 Hz, 1H), 7.33 (t, J = 7.4 Hz, 1H), 7.17 (d, J =
7.4 Hz, 2H), 2.26 (s, 6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
202.4, 141.4, 134.6, 134.3, 134.2, 133.9, 132.5, 130.8, 128.8, 128.6, 127.7,
126.6, 126.2, 124.6, 19.5; MS (EI, 70 eV) m/z (% rel intensity, ion) 260
(75, Mþ), 259 [49, (Mþ - H)], 245 [13, (Mþ - Me)], 127 (100). Anal.
Calcd for C19H16O: C, 87.66; H, 6.19. Found: C, 87.42; H, 6.17.
(2,6-Dimethoxyphenyl)(2,6-dimethylphenyl)methanone
(3db; Table 1, Entry 8; Table 3, Entry 8 and Table 5, Entry
δ (ppm) 7.53-7.38 (m, 3H), 7.35-7.19 (m, 2H), 6.98 (t, J = 7.8 Hz,
2H), 2.66 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 190.7, 159.8
(dd, J = 252, 7.1 Hz), 140.1, 136.5, 132.7, 132.2, 132.1, 131.8 (t, J = 9.6
Hz), 125.8, 120.6 (t, J = 18.3 Hz), 111.8 (m), 21.6; MS (EI, 70 eV) m/z
(% rel intensity, ion) 232 (30, Mþ), 212 [100, (Mþ - HF)], 183 (67),
141 [66, (Mþ - Tol)], 113 (65). Anal. Calcd for C14H10F2O: C, 72.41;
H, 4.34. Found: C, 72.62; H, 4.35.
(2-Methoxyphenyl)-1-naphthylmethanone (3ba; Table 1,
Entry 2). White solid: mp 70-72 °C; 1H NMR (300 MHz, CDCl3) δ
8.51 (d, J = 7.8 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.78 (d, J = 7.0 Hz, 1H),
7.52-7.29 (m, 6H), 6.93 (t, J = 7.4 Hz, 1H), 6.85 (d, J = 8.3 Hz, 1H),
3.48 (s, 3H); 13C NMR (75.5 MHz, CDCl3) δ 197.8, 158.3, 136.9,
133.8, 132.8, 132.2, 130.8, 130.1, 129.6, 128.3, 127.5, 126.2, 125.9, 124.3,
120.5, 112.0, 55.7; MS (EI, 70 eV) m/z(% relintensity, ion) 262(45, Mþ),
247 [13, (Mþ - Me)], 231 [16, (Mþ -OMe)], 135 [80, (Mþ - Naph)],
127 (100). Anal. Calcd for C18H14O2: C, 82.42; H, 5.38. Found: C, 82.33;
H, 5.40.
(2,6-Dimethoxyphenyl)(2-methoxyphenyl)methanone
(3bb; Table 4, Entry 4).26. White solid: mp 132-134 °C; 1H NMR
(300 MHz, CDCl3) δ (ppm) 7.71-7.67 (dd, J = 8.0, 2.0 Hz, 1H), 7.43
(m, 1H), 7.26 (t, J = 8.4 Hz, 1H), 6.97-6.91 (m, 2H), 6.56 (d, J = 8.4 Hz,
2H), 3.72 (s, 3H), 3.67 (s, 6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
193.7, 159.6, 157.3, 133.8, 132.1, 130.0, 128.1, 121.4, 120.1, 112.3, 104.1,
55.9.
6
1
6). . White solid: mp 140-142 °C; H NMR (300 MHz, CDCl3) δ
(ppm) 7.23 (t, J = 8.4 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H), 6.88 (d, J = 7.5
Hz, 2H), 6.47 (d, J = 8.4 Hz, 2H), 3.59 (s, 6H), 2.13 (s, 6H); 13C NMR
(75.5 MHz, CDCl3) δ (ppm) 199.1, 158.8, 142.4, 135.4, 132.1, 128.5,
127.7, 120.9, 104.7, 56.0, 19.6.
(2,6-Dimethylphenyl)(3-methylthiophen-2-yl)methanone
(3dd; Table 1, Entry 13). White solid: mp 94-96 °C; 1H NMR (300
MHz, CDCl3) δ (ppm) 7.39 (d, J = 4.8 Hz, 1H), 7.13 (t, J = 7.5 Hz, 1H),
6.98 (d, J = 7.5 Hz, 2H), 6.86 (d, J = 4.9 Hz, 1H), 2.23 (br, 3H), 2.12 (s,
6H); 13C NMR: (75.5 MHz, CDCl3) δ (ppm) 192.7, 145.5, 141.2, 138.0,
133.8, 132.8, 132.5, 128.9, 127.6, 19.1, 16.0; MS (EI, 70 eV) m/z (% rel
(2-Methoxyphenyl)(2,4,6-trimethylphenyl)methanone
27
1
(3bc; eq 3). . Pale yellow solid: mp 110-112 °C; H NMR (300
MHz, CDCl3) δ (ppm) 7.53 (d, J = 7.5 Hz, 1H), 7.47 (t, J = 7.8 Hz, 1H),
6.98-6.91 (m, 2H), 6.83 (s, 2H), 3.76 (s, 3H), 2.29 (s, 3H), 2.10 (s,
6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm) 199.7, 159.5, 139.4, 138.0,
134.2, 133.9, 132.2, 128.2, 128.1, 120.4, 112.3, 55.9, 21.1, 19.4.
(2-Methoxyphenyl)(3-methylthiophen-2-yl)methanone
intensity, ion) 230 (16, Mþ), 215 [100, (Mþ - Me)], 200 [31, (Mþ
-
1
2Me)]. Anal. Calcd for C14H14OS: C, 73.01; H, 6.13. Found: C, 72.86; H,
6.10.
(3bd; Table 1, Entry 12). White solid: mp 72-74 °C; H NMR
(300 MHz, CDCl3) δ (ppm) 7.35 (t, J = 7.8 Hz, 2H), 7.26 (d, J = 7.4
Hz,1H), 6.95-6.80 (m, 3H), 3.70 (s, 3H), 2.34 (s, 3H); 13C NMR (75.5
MHz, CDCl3) δ (ppm) 188.9, 156.7, 145.5, 137.6, 132.3, 131.6, 131.5,
130.8, 128.5, 120.4, 111.5, 55.7, 16.3; MS (EI, 70 eV) m/z (% rel
(2,6-Difluorophenyl)(2,6-dimethylphenyl)methanone (3de;
Table 1, Entry 16). White solid: mp 109-11 °C; 1H NMR (300 MHz,
CDCl3) δ(ppm) 7.35 (m, 1H), 7.20 (t, J =7.6Hz, 1H), 7.03 (d, J =7.5 Hz,
2H), 6.91 (m, 2H), 2.22 (s, 6H); 13C NMR (75.5 MHz, CDCl3) δ (ppm)
194.1, 160.8 (dd, J = 257, 6.3 Hz), 141.1, 134.6, 133.3 (t, J = 10.8 Hz),
129.6, 128.1, 119.0 (t, J = 16.0 Hz), 112.3 (m), 19.5; MS (EI, 70 eV) m/z
(% relintensity, ion) 246(11, Mþ), 226 [100, (Mþ - HF)], 211 (37), 141
(54), 133 (28). Anal. Calcd for C15H12F2O: C, 73.16; H, 4.91. Found: C,
73.33; H, 4.92.
intensity, ion) 232 (39, Mþ), 231 [90, (Mþ - H)], 217 [100, (Mþ
-
Me)], 201 [33, (Mþ - OMe)]. Anal. Calcd for C13H12O2S: C, 67.21; H,
5.21. Found: C, 67.01; H, 5.25.
(2,6-Difluorophenyl)(2-methoxyphenyl)methanone (3be;
Table 1, Entry 15). White solid: mp 52-54 °C; 1H NMR (300 MHz,
CDCl3) δ (ppm) 7.78 (dd, J = 7.1, 2.0 Hz, 1H), 7.52 (m, 1H), 7.34 (m,
1H), 7.04 (t, J = 7.3 Hz, 1H), 6.94-6.87 (m, 3H), 3.64 (s, 3H); 13C
NMR (75.5 MHz, CDCl3) δ (ppm) 187.7, 159.9 (dd, J = 252, 7.5 Hz),
159.6, 134.9, 131.3, 131.1 (t, J = 10.2 Hz), 127.7, 120.7, 120.3 (t, J = 20.0
Hz), 112.0, 111.4 (m), 55.7; MS (EI, 70 eV) m/z (% rel intensity, ion)
248 (30, Mþ), 141 [63, (Mþ - Ans)], 135 [100, (Mþ - C6H3F2)].
Anal. Calcd for C14H10F2O2: C, 67.74; H, 4.06. Found: C, 67.95; H,
4.10.
Recovering Method for Trialkyltin Chlorides
Trimethyltin Chloride. The aqueous solution (∼10 mL for 1.0
mmol scale reaction) was saturated with KF, 10 mL of Et2O was added,
and the mixture was vigorously shaken, then the precipitated trimethyl-
tin fluoride (0.297 g, 81%) was removed by filtration at reduced pressure
and stored for future reconversion to the chloride by treatment with an
excess of NaCl in THF, according to the method reported by Mitchell.28
Tributyltin Chloride. After chromatographic procedure (10.0 g
of silica gel for a 1.00-mmol scale reaction) the column was eluted with
100 mL of THF. The silica was dried with compressed air and poured
(2-Isopropyl-4-methoxy-5-methylphenyl)-1-naphthylmeth-
anone (3ca; Table 1, Entry 3 and Table 5, Entry 2). Pale yellow
oil: 1H NMR (300 MHz, CDCl3) δ (ppm) 8.21 (d, J = 8.4 Hz, 1H), 7.80
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The Journal of Organic Chemistry
ARTICLE
into a 100-mL round-bottomed flask fitted with a condenser and a
nitrogen T-joint. NaCl (293 mg, 5.00 mmol) and 50 mL of dry THF
were added and the mixture was heated at reflux with stirring for 4 days.
It was then allowed to cool and poured into a chromatography column
plugged with a small piece of cotton wool. All of the THF was drained
with air pressure and then the column was eluted with ether (2 ꢀ 50
mL). The combined ethers were concentrated in vacuo giving tributyltin
chloride in ca. 80% with respect to the starting aryltributylstannane.
(13) We inform the best result obtained after working at different
temperatures.
(14) It should be mentioned that anisole reacted with 2a, 2d, and 2e,
under similar reaction conditions, giving the corresponding p-isomers as
main products.
(15) Neumann, W. P.; Hillg€artner, H.; Baines, K. M.; Dicke, R.;
Vorspohl, K.; Kowe, U.; Nussbeutel, U. Tetrahedron 1989, 45, 951.
(16) Gore, P. H. Aromatic Ketone Synthesis. In Friedel-Crafts and
Related Reactions; Olah, G. A., Ed.; Wiley- Interscience: New York, 1964;
Vol. III, p 1.
(17) The actual reaction conditions of the isomerization of 3db
(18) Kashiwabara, T.; Tanaka, M. J. Org. Chem. 2009, 74, 3958.
(19) For reviews see: (a) Ranu, B. C. Eur. J. Org. Chem. 2000, 2347.
(b) Nair, V.; Ros, S.; Jayan, C. N.; Pillia, B. S. Tetrahedron 2004, 60, 1959.
(c) Augꢀe, J.; Lubin-Germain, N.; Uziel, J. Synthesis 2007, 1739. (d)
Yadav, J. S.; Antony, A.; George, J.; Reddy, B. V. Eur. J. Org . Chem. 2010,
591.
(20) Davies, A. G. J. Chem. Soc., Perkin Trans. 1 2000, 1997.
(21) Yammal, C. C.; Podestꢀa, J. C.; Rossi, R. A. J. Org. Chem. 1992,
57, 5720.
(22) Faraoni, M. B.; Koll, L. C.; Mandolesi, S. D.; Zu~niga, A. E.;
Podestꢀa, J. C. J. Organomet. Chem. 2000, 613, 236.
(23) Schaeffer, C. D., Jr.; Zuckerman, J. J. J. Organomet. Chem. 1975,
99, 407.
(24) Ferrer Flegeau, E.; Popkin, M. E.; Greaney, M. F. J. Org. Chem.
2008, 73, 3303.
(25) Fernꢀandez-Ibꢀa~nez, M. A.; Maciꢀa, B.; Minnaard, A. J.; Feringa,
B. L. Org. Lett. 2008, 10, 4041.
’ ASSOCIATED CONTENT
S
Supporting Information. General experimental meth-
b
1
ods, physical and spectroscopic data of compound 1c, H and
13C NMR spectra of compounds 1c, 3ab, 3ae, 3ba, 3bd, 3be, 3ca,
3cb, 3da, 3dd, and 3de, and 1H NMR spectra of compounds 3aa,
3ac, 3bb, 3bc, 3db, and 3dc. This material is available free of
charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*Phone: 54 291 4595100. Fax: 54 291 4595187. E-mail: teresa.
lockhart@uns.edu.ar.
Notes
§Member of CIC.
(26) Charlton, J. L.; Sayeed, V. A.; Koh, K.; Lau, W. F.; Lai, H. K.;
Bell, A. R. J. Agric. Food Chem. 1990, 38, 1719.
’ ACKNOWLEDGMENT
(27) Fuson, R. C.; Mon, M. T. J. Org. Chem. 1961, 26, 756.
(28) Mitchell, T. N.; Kwetkat, K.; Godry, B. Organometallics 1991,
10, 1633.
This work was partially supported by CONICET, CIC,
ANPCYT, and the Universidad Nacional del Sur, Bahía Blanca,
Argentina. CONICET is thanked for a research fellowship to
M.J.L.F.
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(10) The starting arylstannanes were prepared by known procedures
(see the Supporting Information).
(11) Anisole reacted with 2b and 2c under similar reaction condi-
tions. After 2 h at 180 °C, ketones 4bb or 4bc were obtained as the only
products.
(12) We inform the best result obtained after working at different
concentrations.
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