Experimental and DFT study on the indium-mediated synthesis of benzophenones via arylstannanes

Article abstract of DOI:10.1039/c4ra07305c

Experimental results of the solvent-free, indium-promoted reaction of aroyl chlorides with arylstannanes showed a narrow scope; its efficiency depends both on the extent of methylation in the latter and on the nature, number and position of the substituents in the former. With the purpose of explaining experimental results, a theoretical analysis with DFT methods was performed for a set of selected cases. This journal is

Full text of DOI:10.1039/c4ra07305c

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Experimental and DFT study on the indium-
mediated synthesis of benzophenones via
arylstannanes†
Cite this: RSC Adv., 2014, 4, 49079
Marcos J. Lo Fiego, Viviana B. Dorn,‡* Mercedes A. Badajoz, Marıa T. Lockhart*
´
and Alicia B. Chopa§
Received 18th July 2014
Accepted 18th September 2014
Experimental results of the solvent-free, indium-promoted reaction of aroyl chlorides with arylstannanes
showed a narrow scope; its efficiency depends both on the extent of methylation in the latter and on
the nature, number and position of the substituents in the former. With the purpose of explaining
experimental results, a theoretical analysis with DFT methods was performed for a set of selected cases.
DOI: 10.1039/c4ra07305c
www.rsc.org/advances
reaction of bulky aroyl chlorides with bulky arylstannanes, in
the synthesis of severely hindered benzophenones; moreover,
Introduction
4e
Ketones are vital building blocks in organic synthesis as well as we have also established that it is a promoter of the solvent-free
an important functionality found in pharmaceutical reaction of alkanoyl chlorides with arylstannanes, in the
4
h
compounds. The Friedel–Cras (F–C) acylation of aromatic synthesis of primary, secondary and tertiary alkyl aryl ketones.
compounds is the most frequent route for the synthesis of The reactions are carried out under mild and neutral condi-
1
aromatic ketones. However, it has intrinsic limitations such as tions, being their striking advantages (i) the use of no solvent,
the substituent-directing effects, the reactivity substrate (ii) readily available, non-toxic and reusable metal catalyst; (iii)
requirements and the fact that recovery and recycling of the accessible substrates and reactants and (iv) the specicity of the
catalyst is seldom possible aer aqueous work-up and a reaction. On the latter point, it is worth noting that, whether the
large amount of toxic waste is generated. On the other hand, reaction proceeds via a free-radical or ionic mechanism, the
Pd-catalyzed cross-coupling reactions of acyl halides with arylstannane plays a key role in regards to the regioselectivity of
organometallic reagents provide a direct procedure for the the benzophenones synthesis. The high ipso reactivity makes it
2
synthesis of isomeric ketones; a drawback is that Pd-catalysts possible to carry out aromatic substitution under mild condi-
are expensive and they are not recovered. Arylstannanes are tions overriding the normal directive effect of substituents. This
valuable reagents for the regiospecic generation of C–C bonds. is ascribed mainly to the stabilization of the cyclohexadienyl
In the last years, we have been involved in the synthesis of radical or cation intermediates by hyperconjugation between
3
arylstannanes as well as in their application as intermediates in the singly occupied or unoccupied 2p orbital and the b-C–Sn
4
organic synthesis focused, especially, in the development of bond (oen referred as b-effect). Furthermore, unlike the cor-
new procedures for the regiospecic synthesis of aryl ketones responding homolytic substitution of hydrogen, the stannyl
4
b–e
through catalyst-free processes.
radical should be rapidly lost from the cyclohexadienyl inter-
6
The advance of indium-mediated synthetic methods has mediate without the need for any oxidant. In this connection
grown up in the recent literature due to the special properties of we sought to establish the scope of this solvent free approach,
indium metal. It is unaffected by air, moisture or oxygen at with the ultimate goal of developing a general method for the
5
ambient temperature and, most importantly, the element itself synthesis of benzophenones. Thus, we initiated a systematic
is without any apparent toxicity. In this respect, we have study of the reaction between a series of representative benzoyl
established that indium metal is a promoter of the solvent-free chlorides (Fig. 1, 1a–g) with a series of arylstannanes (Fig. 1, 2a–
d) and herein, we report the unexpected experimental results
and a possible theoretical interpretation of this reaction.
INQUISUR, Departamento de Qu ´ı mica, Universidad Nacional del Sur, Avenida Alem
253, 8000 Bah ´ı a Blanca, Argentina. E-mail: lockhart@criba.edu.ar; vdorn@uns.
edu.ar; Fax: +54 291 459 5187; Tel: +54 291 459 5187
Electronic supplementary information (ESI) available: xyz coordinates and total
1
†
1
13
Results and discussion
energies in atomic units for all of the calculated structures and copy of H and
C
NMR spectra of unknown compounds 3ed, 3dd and 3fd. See DOI:
We initiated our studies with the reaction between benzoyl
chloride (1a) and tributylphenylstannane (2a) as a model
system. Unexpectedly, aer long reaction times (24 h), even
1
‡
§
0.1039/c4ra07305c
Member of CONICET.
Member of CIC.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 49079–49085 | 49079

View Article Online
RSC Advances
Paper
Fig. 1 Starting materials: benzoyl chlorides and arylstannanes.
traces of the desired ketone were not detected although working (2,6-dimethoxy) are more reactive than isomer 1d (3,5-dimethoxy)
ꢀ
at higher temperatures (50–100 C) or employing an excess of 1a. and even than 1f (3,4,5-trimethoxy).
Next, and based on our previous experience where aryl-
It is important to note that a control experiment showed that
stannanes containing electron-releasing substituents were no reaction occurred in the absence of In(0). Besides, it is
4
e,h
proved to be adequate substrates under this protocol,
carried out a series of reactions between 1a and arylstannanes capable of promoting single-electron transfer (SET) processes.
b–d (Table 1, entries 1 to 3). The results obtained showed that To prove whether acyldestannylations proceeded through a
we known that, because of its low rst ionization potential, In(0) is
8
2
ꢀ
7
working at 80 C (24 h), meanwhile 2b was unreactive, the polar or a free radical pathway, we performed the reaction of 1f
reaction of 2c and 2d with 1a yielded the corresponding ketones and 2d in the presence of 0.5 equiv. of di-tert-butyl nitroxide
3ac and 3ad, although in really low yields (traces and 20%, (DTBN) as radical scavenger. Compared with a blank reaction,
respectively), and substantial amounts of reactant were recov- we noticed that the addition of DTBN had a dramatic retarda-
ered. It should be mentioned that 3ad was obtained together tion effect and only traces of ketone 3fd were detected recov-
with the undesired isomeric ketone (2,4-dimethylphenyl)phenyl ering the starting substrate. On the basis of these results, we
methanone (5%), product of the direct aroylation of the believe that the reaction proceeds initially through a SET from
aromatic ring followed by protodestannylation. Likewise, the In(0) to the aroyl chloride with generation of an acyl radical and
reaction of arylstannanes 2a to 2d with (4-methoxy)benzoyl In(I) chloride salt. The acyl radical thus formed reacts with the
chloride (1b) gave the corresponding ketones, (traces up to 25%) arylstannane through a homolytic ipso aromatic substitution
4
e
(
(
(
Table 1, entries 4 to 7). In contrast, the reaction of 2d with affording the ketone (Scheme 1). The high ortho-selectivity
4-nitro)benzoyl chloride (1c) was negative even aer 72 h make it reasonable to speculate that the formation of the
Table 1, entry 8).
cyclohexadienyl radical intermediate is the rate determining
These preliminary results showed that the nature of the step (RDS) which is conditioned by the degree of fragmentation
benzoyl chloride is an important parameter in these reactions of the acyl radical anion and the reactivity of the corresponding
and that a p-electron releasing group attached to the aromatic acyl radical (Scheme 1).
ring increased its reactivity (entries 1–3 vs. 5–7 and entry 7 vs. 8).
Furthermore, the reactions carried out with arylstannane 2d tions proceed through an electron transfer (ET) pathway
gave better yields (entries 3 and 7). generating an acyl radical (Scheme 1), prompted us to study, in
The unexpected results together with the fact that the reac-
Based on these outcomes we considered it interesting to more detail, the ET process involved using density functional
study the reactivity of arylstannane 2d towards different theory (DFT) calculations. For this purpose, we simplied the
commercially available benzoyl chlorides containing two or reactive system and theoretically studied the neutral acyl chlo-
three methoxy groups in diverse positions, such as (3,5-dime- rides and the corresponding radical anions of compounds 1a,
thoxy)benzoyl chloride (1d), (3,4-dimethoxy)benzoyl chloride 1c and the dimethoxybenzoyl chlorides isomers 1d and 1g as
9
(
1e) and (3,4,5-trimethoxy)benzoyl chloride (1f). The reactions, representative compounds. The density functional theory
10
which were quenched at 2 h in order to compare results with calculations were performed with the B3LYP functional and
4e
those we have formerly reported, gave the corresponding the 6-31+G* basis set, which is known to be an appropriate
1
1
ketones 3dd, 3ed and 3fd with 6%, 48% and 32% yield, methodology for the theoretical studies of electron affinities
12
13
respectively (Table 1, entries 9 to 11). In a previous work we have and electronic properties of radicals and radical anions.
informed the synthesis of the bulky ketone 3gd (55%; Table 1, Adiabatic electron affinity (AEA) can be used as a magnitude
entry 12) under a similar protocol. So, it is evident that the of the reactivity of a molecule toward a SET process. Table 2
effectiveness of the reaction depends mainly on the relative shows AEA of the neutral benzoyl chlorides, obtained as the
position of the methoxy groups in the aromatic ring rather than difference in the energies between the neutral molecule and the
their number. Thus, isomers 1e (3,4-dimethoxy) and 1g radical anion with full geometry optimization of both species,
4
e
49080 | RSC Adv., 2014, 4, 49079–49085
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Table
chlorides
1 Indium-mediated reactions of arylstannanes with aroyl Table 1 (Contd.)
a
a
0
0
b
Entry ArCOCl Ar SnR
3
Time (h) ArCOAr
Yield (%)
a
0
0
b
Entry ArCOCl Ar SnR
3
Time (h) ArCOAr
Yield (%)
d,f
1
2
1a
1a
2b
2c
24
0
11
1f
2d
2
32
24
24
Traces
g
12
1g
1g
2d
2d
2
55
49
c
3
4
1a
1b
2d
2a
20
g,h
13
2
3gd
a
ꢀ
All reactions were conducted at 80 C (oil bath) in solventless
conditions using 1.2 equiv. of 1, 1.0 equiv. of 2 and 1.0 equiv. of
indium metal. Determined by GC-MS (using tetradecane as internal
b
c
standard). Together wdith the regioisomer [(2,4-dimethylphenyl)-
24
24
24
24
72
Traces
phenyl methanone, 5%]. Traces of mesitylene were detected (GC-MS)
and large amounts of unreacted starting materials were recovered.
[(3,4-dimethoxyphenyl)(2,4-
dimethylphenyl)methanone, 4%]. Together with the regioisomer
e
Together
with
the
regioisomer
f
g
[
(3,4,5-trimethoxyphenyl)(2,4-dimethylphenyl)methanone, 10%]. Ref. 4e.
h
Performed with 0.2 equiv. of indium metal.
5
6
7
8
1b
1b
1b
1c
2b
2c
2d
2d
4
9
25
0
d
9
1
1d
1e
2d
2d
2
2
6
Scheme 1
d,e
0
48
11b–d
including the zero point energy (ZPE) corrections (eqn (1)).
As expected, benzoyl chlorides showed differences in energy.
AEA ¼ E(optimized neutral) ꢁ E(optimized radical anion) (1)
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 49079–49085 | 49081

View Article Online
RSC Advances
Paper
16
Table 2 Adiabatic electron affinities energy (B3LYP/6-31+G*) for 1d gives the product in only 6% yield. Taking this in account,
different benzoyl chlorides
the goal of this computational study is to analyze the corre-
sponding radical anions, as intermediates in the substitution,
bearing in mind the spin density and fragmentation process as
Adiabatic EAs
energy (eV)
Benzoyl chlorides
possible factors responsible for the observed differences. As can
be seen from Fig. 2, there are no differences in the unpaired
electron of both radical anions. With respect to the fragmen-
tation process, once the neutral acyl chloride gain an electron
from In(0) (inter-ET), the reaction may follow two mecha-
2
0
.37
.98
13a,14b
nisms:
CO–Cl bond breaks as the benzoyl radical anion is being formed
inter-DET); (ii) a stepwise mechanism, where takes place an
(i) a concerted dissociative pathway where the
(
intramolecular dissociative ET (intra-DET) from the p system to
the s* CO–Cl bond once the benzoyl radical anion is formed
(Scheme 1). Considering that, we evaluated the potential energy
surfaces (PES) for the dissociation of both intermediates. Our
results indicate that the formation of the benzoyl radical from
1
d occurs exothermically (stepwise mechanism) through a
0
.89
radical anion intermediate, being the activation energy 8.1 kcal
ꢁ
1
mol (ref. 17) (Fig. 3). On the other hand, the fragmentation of
the radical anion 1g takes place without activation energy
generating the corresponding radical by a spontaneous disso-
ciative electron transfer (inter-DET) (Scheme 1).
1g
0.58
As can be seen from Fig. 4, the main geometric difference
between both radical anions isomers is that radical anion 1g
shows an out of plane distortion from the optimal sp dihedral
The presence of an electron-withdrawing group attached to
the aromatic ring (1c) increases the stability of the p-system.
2
14
1
2
ꢀ
ꢀ
18
angle Cl–CO–C –C from 0 to ꢁ20.5 , probably due to steric
repulsion with the ortho-methoxy substitutents. The SOMO MO
shows that this distortion could facilitate the cleavage of this
2
Evidence of this is the shortening of the C–NO bond in the
13a,14b
˚
˚
radical anion (1.40 A) with respect to the neutral (1.48 A).
Thus, the electron transfer (ET-inter) process is favored, by
increasing the adiabatic electron affinity of the substrate. The
unreactivity of derivative 1c is related to the distribution of spin
1
4b,19
radical anion,
being more efficient the intra-DET process
since this spatial geometric arrangement increases the inter-
action and the overlap of the p and s* orbitals in comparison to
the planar radical anion 1d.
13a,d,14b
density,
a relevant factor for reactions that proceed
15
through ET processes. Unlike radical anions 1d and 1g, once
the corresponding radical anion is generated in 1c, the
unpaired electron is located mainly on the nitro function rather
than on the carbon center of the acyl group (Fig. 2); therefore,
even when the 1c radical anion was efficiently generated, the
Experimental section
General experimental methods
expected fragmentation does not take place and the acyl radical All reactions were carried out under a dry nitrogen atmosphere.
is not generated.
Acid chlorides were commercially available and fractionally
The situation for isomers 1d and 1g is different; although distilled under nitrogen or recrystallized from hexane before
both have, as expected, similar electron affinities, their behavior use. Aryltributylstannanes 2a–c were prepared by trans-
towards the most reactive arylstannane 2d is completely metallation of the appropriate Grignard reagents with tribu-
different. Thus, while 1g gives the ketone in a good yield (55%), tyltin chloride in anhydrous THF. Aryltrimethylstannane 2d was
obtained from the corresponding commercial aryl chloride by
ꢁ
ꢁ
ꢁ
Fig. 2 Gas phase B3LYP/6-31+G* spin density (orange, isosurface of 0.02) for 1cc , 1dc and 1gc .
49082 | RSC Adv., 2014, 4, 49079–49085
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
mmol of arylstannane 2 and indium powder (1.0 mmol) under a
nitrogen gas stream. The system was purged with nitrogen by
means of three pump-ll cycles and then the heterogeneous
ꢀ
reaction mixture was stirred at 80 C (oil bath) for the time
indicated in Table 1. Aer addition of 10% (m/v) solution of
NaOH (2 mL) and 10 mL 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 Na
GC/MS.
2 4
SO , ltered and analyzed by GC and
22
(2-Methylphenyl)phenylmethanone (3ac). MS-EI, m/z (%
+
+
+
rel. intensity, ion): 196 (57, M ), 195 [89, (M –H)], 178 [16, (M –
+
+
2
H O)], 119 [30, (M –Ph)], 105 [29, (M –Tol)], 91 (56), 77 (100).
23
(2,6-Dimethylphenyl)phenylmethanone (3ad). MS-EI, m/z
+
+
(
(
% rel. intensity, ion): 210 (33, M ), 209 [40, (M –H)], 195 [20,
M –Me)], 133 [23, (M –Ph)], 105 [42, (M –C
+
+
+
6 4 2
H Me )], 77 (100).
21
(4-Methoxyphenyl)phenylmethanone (3ba). MS-EI, m/z (%
+
+
rel. intensity, ion): 212 (31, M ), 135 [100, (M –Ph)], 105 [12,
+
(
M –Ans)], 92 (22), 77 (54).
4-Methoxylphenyl)(3-methylphenyl)methanone (3bb). MS
24
(
+
+
(
EI, 70 eV) m/z (% rel. intensity, ion): 226 (27, M ), 211 [6, (M –
+
+
Me)], 135 [100, (M –Tol)], 119 [3, (M –Ans)], 92 (25), 77 (22).
21
Fig. 3 Gas phase B3LYP/6-31+G* potential energy profile for disso-
(4-Methoxylphenyl)(2-methylphenyl)methanone (3bc). MS
ꢁ
20
+
+
ciation of 1dc . Spin densities are shown in orange (isosurface of (EI, 70 eV) m/z (% rel. intensity, ion): 226 (23, M ), 225[35, (M –
0
.02).
+
+
+
H)], 211 [12, (M –Me)], 135 [100, (M –Tol)], 119 [5, (M –Ans)], 92
29), 77 (18).
4-Methoxyphenyl)(2,6-dimethylphenyl)methanone (3bd).
(
22
(
photostimulated reaction with Me
according to the literature procedures.
3
SnNa in liquid ammonia,
+
MS (EI, 70 eV) m/z (% rel. intensity, ion): 240 (34, M ), 239 [46,
21
+
+
+
(
M –H)], 225 [24, (M –Me)], 209 [100, (M –OMe)], 135 (77), 105
The products were identied unambiguously by comparing
(30), 92 (47), 77 (91).
their retention times and mass spectra with those of authentic
(3,5-Dimethoxyphenyl)(2,6-dimethylphenyl)methanone (3dd).
4
e
compounds obtained by known procedures, using a GC/MS
instrument (HP5-MS capillary column, 30 m ꢂ 0.25 mm ꢂ 0.25
mm) equipped with 5972 mass selective detector operating at 70
ꢀ
1
3
Yellowish solid: mp 83–86 C; H NMR (300 MHz, CDCl )
d(ppm) 7.20 (t, J ¼ 7.6 Hz, 1H), 7.05 (d, J ¼ 7.6 Hz, 2H), 6.95 (d, J
¼
2.3 Hz, 2H), 6.67 (t, J ¼ 2.3 Hz, 1H), 3.80 (s, 6H), 2.13 (s, 6H);
ꢀ
ꢀ
ꢁ1
eV (EI). Program: 50 C for 2 min with increase 10 C min to 13
C NMR (75.5 MHz, CDCl ) d(ppm) 200.3 (CO), 161.3 (C), 139.7
3
ꢀ
2
80 C.
(C), 139.2 (C), 134.3 (C), 128.9 (CH), 127.7 (CH), 107.2 (CH),
1
06.1 (CH), 55.7 (CH
3 3
), 19.5 (CH ); MS (EI, 70 eV) m/z (% rel.
+
+
intensity, ion): 270 (100, M ), 255 [54, (M –Me)], 105 (90), 92
General procedure for indium-mediated reactions
(19), 77 (99); Anal. calcd for C17
H
18
O
3
: C, 75.53; H, 6.71. Found:
In a ame dried Schlenk tube (tted with a teon plug valve) 1.2 C, 75.66; H, 6.53.
mmol of acid chloride 1 was added to a stirred mixture of 1.0
ꢁ
ꢁ
ꢁ
Fig. 4 B3LYP/6-31+G* geometry of 1gc and SOMO MOs (orange and blue, isosurface of 0.02) of 1gc and 1dc .
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 49079–49085 | 49083

View Article Online
RSC Advances
Paper
(
3,4-Dimethoxyphenyl)(2,6-dimethylphenyl)methanone (3ed). systems that imply radicals and radical anions involved in ET
ꢀ
1
White solid: mp 82–84 C; H NMR (300 MHz, CDCl
.61 (d, J ¼ 1.6 Hz, 1H), 7.22 (t, J ¼ 7.7 Hz, 1H), 7.17 (dd, J ¼ 8.4
Hz; J ¼ 1.6 Hz, 1H), 7.07 (d, J ¼ 7.7 Hz, 2H), 6.80 (d, J ¼ 8.4 Hz,
3
) d(ppm) processes.
7
Acknowledgements
1
3
1
H) 3.94 (s, 3H), 3.93 (s, 3H), 2.13 (s, 6H); C NMR (75.5 MHz,
CDCl ) d(ppm) 199.2 (CO), 154.0 (C), 149.6 (C), 140.0 (C), 134.3 We are grateful for nancial support provided by CONICET
3
(
1
(
(
C), 130.6 (C), 128.7 (CH), 127.6 (CH), 125.6 (CH), 110.3 (CH), (Consejo Nacional de Investigaciones Cient ´ı cas y T ´e cnicas),
10.3 (CH), 56.2 (CH ), 56.2 (CH ), 19.5 (CH ); MS (EI, 70 eV) m/z ANPCyT (Agencia Nacional de Promoci ´o n Cient ´ı ca y Tec-
3
3
3
+
+
% rel. intensity, ion): 270 (62, M ), 255 [16, (M –Me)], 240 [100, nol ´o gica), CIC (Comisi ´o n de Investigaciones Cient ´ı cas) and
+
M –2Me)], 105 (27), 92 (9), 79 (51); anal. calcd for C17
H
18
O
3
: C, SGCyT-UNS (Secretar ´ı a General de Ciencia y T ´e cnica – Uni-
75.53; H, 6.71. Found: C, 75.64; H, 6.74.
versidad Nacional del Sur) from Argentina. CONICET is thanked
(
3,4,5-Trimethoxyphenyl)(2,6-dimethylphenyl)methanone (3fd). for a research fellowship to MLF. The authors would like to
ꢀ
1
White solid: mp 57–60 C; H NMR (300 MHz, CDCl
.22 (t, J ¼ 7.6 Hz, 1H), 7.09 (d, J ¼ 7.4 Hz, 2H), 7.06 (s, 2H), 3.93 manuscript.
3
) d(ppm) thanks Prof. A. B. Pierini for her feedback and advisory with this
7
(
1
3
s, 3H), 3.81 (s, 6H), 2.14 (s, 6H); C NMR (75.5 MHz, CDCl )
3
d(ppm) 199.4 (CO), 153.5 (C), 143.4 (C), 139.6 (C), 134.3 (C),
Notes and references
1
32.4.9 (C), 128.9 (CH), 127.7 (CH), 107.0 (CH), 66.1 (CH
CH ), 19.5 (CH ); MS (EI, 70 eV) m/z (% rel. intensity, ion): 300
100, M ), 285 [20, (M –Me)], 270 [96, (M –2Me)], 225 (21), 133
32), 105 (60), 92 (7), 77 (58); anal. calcd for C18 : C, 71.98;
3
), 56.4
(
(
(
3
3
1 (a) M. B. Smith and J. March, March's Advanced Organic
Chemistry, John Wiley, New York, 6th edn, 2007; (b)
R. C. Larock, Comprehensive Organic Transformations, Wiley,
VCH, New York, 1999.
+
+
+
20 4
H O
H, 6.71. Found: C, 72.06; H, 6.84.
2
3
For a review see: K. Dieter, Tetrahedron, 1999, 55, 4177.
(a) A. B. Chopa, M. T. Lockhart and G. F. Silbestri,
Organometallics, 2000, 19, 2249; (b) A. B. Chopa,
M. T. Lockhart and G. F. Silbestri, Organometallics, 2001,
Computational procedure
25
The calculations were performed with Gaussian09. The initial
conformational analysis of selected compounds was performed
with the semiempirical AM1 method. The geometry of the most
stable conformers thus obtained was used as starting point for
the B3LYP studies of the corresponding benzoyl chlorides and
their radical anions. Zero point energy and thermal energy were
computed at the 6-31+G* level and scaled by a factor 0.986 (ref.
20, 3358; (c) A. B. Chopa, M. T. Lockhart and V. B. Dorn,
Organometallics, 2002, 21, 1425; (d) A. B. Chopa,
M. T. Lockhart and G. F. Silbestri, Organometallics, 2002,
21, 5874; (e) G. F. Silbestri, M. J. Lo Fiego, M. T. Lockhart
and A. B. Chopa, J. Organomet. Chem., 2010, 695, 2578; (f)
G. F. Silbestri, M. T. Lockhart and A. B. Chopa, ARKIVOC,
26) for adiabatic EAs and thermodynamic quantities. The
2011, 210; (g) V. B. Dorn, G. F. Silbestri, M. T. Lockhart,
potential energy surface was inspected through a scan of the
distinguished reaction coordinate. That is, by elongating the
C(O)–Cl bond (steps of 0.01 A each) at B3LYP/6-31+G* level with
full optimization for the remainder degrees of freedom. The
energy prole obtained is shown in Fig. 3. The characterization
of all stationary points was done by Hessian matrix calculations
of geometries obtained with full optimization for a minimum
and by using the QST2 methodology for a transition state. All
A. B. Chopa and A. B. Pierini, New J. Chem., 2013, 37, 1150.
(a) A. B. Chopa, G. F. Silbestri and M. T. Lockhart, J.
Organomet. Chem., 2005, 690, 3865; (b) G. F. Silbestri,
R. Bogel Masson, M. T. Lockhart and A. B. Chopa, J.
Organomet. Chem., 2006, 691, 1520; (c) M. J. Lo Fiego,
M. A. Badajoz, G. F. Silbestri, M. T. Lockhart and
A. B. Chopa, J. Org. Chem., 2008, 73, 9184; (d) M. J. Lo
Fiego, M. T. Lockhart and A. B. Chopa, J. Organomet.
Chem., 2009, 694, 3674; (e) M. J. Lo Fiego, G. F. Silbestri,
A. B. Chopa and M. T. Lockhart, J. Org. Chem., 2011, 76,
4
˚
27
calculations were performed in gas phase.
1
707; (f) C. E. Domini, G. F. Silbestri, B. Fern ´a ndez Band
Conclusions
and A. B. Chopa, Ultrason. Sonochem., 2012, 19, 410; (g)
M. Luong, C. E. Domini, G. F. Silbestri and A. B. Chopa, J.
Organomet. Chem., 2013, 723, 43; (h) M. J. Lo Fiego,
M. A. Badajoz, C. E. Domini, A. B. Chopa and
M. T. Lockhart, Ultrason. Sonochem., 2013, 20, 826.
5 For reviews see: (a) B. C. Ranu, Eur. J. Org. Chem., 2000, 2347;
(b) V. Nair, S. Ros, C. N. Jayan and B. S. Pillia, Tetrahedron,
2004, 60, 1959; (c) J. Aug ´e , N. Lubin-Germain and J. Uziel,
Synthesis, 2007, 1739; (d) J. S. Yadav, A. Antony, J. George
and B. V. Reddy, Eur. J. Org. Chem., 2010, 591; (e)
A. K. Singh, Synlett, 2013, 24, 1457.
Despite the limited scope of this methodology, our results are a
contribution to the research related to the action of metallic
indium as a promoter of free-radical reactions in organic
synthesis. We have observed that the effectiveness of the
synthesis of benzophenones, through the indium-promoted
solvent-free reaction of aroyl chlorides with arylstannanes,
depends not only on the extent of methylation in the latter but,
in a very peculiar way, on the nature, number and position of
the substituents in the former. A good agreement between DFT
calculation and the experimental results was found for the
analyzed cases. In this way the B3LYP functional and the
6 See “Metals as surrogates for hydrogen in organic chemistry:
anything hydrogen can do, a metal can do better”,
A. G. Davies, J. Chem. Soc., Perkin Trans. 1, 2000, 1997.
6-31+G* basis set demonstrated to be an adequate and
computationally economic methodology for studying reactive
49084 | RSC Adv., 2014, 4, 49079–49085
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
7
8
9
This temperature is required to keep an efficient stirring of 20 It should be mentioned that, when the 6-31+G** and 6-
the reaction mixture.
31++G** basis set was applied in the calculations, the spin
density remained almost unchanged.
G. Marin, A. L. Braga, A. S. Rosa, F. Z. Galetto, R. A. Burrow,
H. Gallardo and M. W. Paixao, Tetrahedron, 2009, 65, 4614.
W. Kohn and I. J. Sham, Phys. Rev., 1965, 140, A1133.
21 C. C. Yammal, J. C. Podest ´a and R. A. Rossi, J. Org. Chem.,
1992, 57, 5720.
1
0 (a) C. Lee, W. Yang and R. G. Parr, Phys. Rev. B: Condens. 22 J. R. Schmink and S. W. Krska, J. Am. Chem. Soc., 2011, 133,
Matter Mater. Phys., 1988, 37, 785; (b) A. D. Becke, Phys. 19574.
Rev. A, 1988, 38, 3098; (c) E. Miehlich, A. Savin, H. Stoll 23 B. M. O'Keefe, N. Simmons and S. F. Martin, Org. Lett., 2008,
and H. Preuss, Chem. Phys. Lett., 1989, 157, 200. 10, 5301.
1 (a) S. E. Boesch, A. K. Graon and R. A. Wheeler, J. Phys. 24 W. J. Wu, T. C. Lin, T. Takahashi, F. Y. Tsai and C. Y. Mou,
Chem., 1996, 100, 10083; (b) D. M. A. Vera and ChemCatChem, 2013, 5, 1011.
A. B. Pierini, Phys. Chem. Chem. Phys., 2004, 6, 2899; (c) 25 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
1
M. Puiatti, D. M. A. Vera and A. B. Pierini, Phys. Chem.
Chem. Phys., 2008, 10, 1394; (d) M. Puiatti, D. M. A. Vera
and A. B. Pierini, Phys. Chem. Chem. Phys., 2009, 11, 9013
and references therein.
2 L. E. Peisino and A. B. Pierini, J. Org. Chem., 2013, 78, 4719.
3 (a) A. B. Pierini and D. M. A. Vera, J. Org. Chem., 2003, 68,
M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone,
B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato,
X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng,
J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota,
R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,
O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr.,
J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd,
E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith,
R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell,
J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega,
J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken,
C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli,
J. W. Ochterski, R. L. Martin, K. Morokuma,
V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg,
S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman,
J. V. Ortiz, J. Cioslowski and D. J. Fox, Gaussian 09,
Revision C.01, Gaussian, Inc., Wallingford CT, 2010.
1
1
9191; (b) D. M. A. Vera and A. B. Pierini, Phys. Chem. Chem.
Phys., 2004, 6, 2899; (c) J. G. Uranga, D. M. A. Vera,
A. N. Santiago and A. B. Pierini, J. Org. Chem., 2006, 71,
6
596; (d) X. Asensio, A. Gonz ´a lez-Lafont, J. Marquet,
J. M. Lluch and M. Geoffroy, J. Mol. Struct.: THEOCHEM,
009, 913, 228.
2
1
4 (a) E. R. Vorpagel, A. Streitwieser Jr and S. D. Alexandratos, J.
Am. Chem. Soc., 1981, 103, 3777; (b) A. B. Pierini, J. S. Duca
and M. A. Vera, J. Chem. Soc., Perkin Trans. 2, 1999, 1003.
5 (a) R. A. Rossi and R. H. de Rossi, Aromatic Substitution by the
1
S
RN1 Mechanism, American Chemical Society Monograph
Series, 1983, p. 178; (b) V. B. Dorn, M. A. Badajoz,
M. T. Lockhart, A. B. Chopa and A. B. Pierini, J. Organomet. 26 I. M. Alecu, J. Zheng, Y. Zhao and D. G. Truhlar, J. Chem.
Chem., 2008, 693, 2458; (c) F. Nador, Y. Moglie, A. Ciolino, Theory Comput., 2010, 6, 2872.
A. Pierini, V. Dorn, M. Yus, F. Alonso and G. Radivoy, 27 Although we do not know the effective polarity of the
Tetrahedron Lett., 2012, 53, 3156.
reaction medium, we evaluate the dependence of the
chemical reactivity associated with derivatives 1d and 1g in
condensed phase using the PCM model (S. Miertus, E.
Scrocco and J. Tomasi, Chem. Phys., 1981, 55, 117. S.
Miertus and J. Tomasi, Chem. Phys., 1982, 65, 239. M.
Cossi, V. Barone, R. Cammi and J. Tomasi, Chem. Phys.
Lett., 1996, 255, 327.) implemented in Gaussian09 in three
different solvents (acetone (3 ¼ 20.7), o-dichlorobenzene (3
¼ 9.9), chloroform (3 ¼ 4.7)) thus covering a wide range of
dielectric constants. The evaluation of the obtained
adiabatic electron affinities and activation energy (reported
in the ESI†) allow us to conclude that the gas phase
calculations are a good approach in order to explain the
reactivity of this experimental system.
1
6 Better calculations level has been attempted, enlarging the
basis set to 6-31+G** and 6-31++G**. However, not
substantial changes have been observed. The adiabatic
electron affinity for 1c was 2.37 eV, 2.38 eV and 2.38 eV
using 6-31+G*, 6-31+G** and 6-31++G** respectively.
7 Similar results were obtained with a better calculation level
1
1
1
ꢁ
1
for the AE, 8.1 and 8.0 kcal mol aer applying 6-31+G**
and 6-31++G**, respectively.
ꢀ
ꢀ
8 20.7 and 20.8 were the values obtained for the dihedral
1
2
angle Cl–CO–C –C
with 6-31+G** and 6-31++G**,
respectively.
9 A. B. Pierini and J. S. Duca, J. Chem. Soc., Perkin Trans. 2,
995, 1821.
1
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 49079–49085 | 49085