Regioselectivity of methyl chlorobenzoate analogues with trimethylstannyl anions by radical nucleophilic substitution: Theoretical and experimental study

Article abstract of DOI:10.1039/b9nj00664h

Reactions of methyl 2,5-dichlorobenzoate, methyl 4-chlorobenzoate, methyl 2-chlorobenzoate and methyl 3-chlorobenzoate with Me₃Sn^- ions gave the corresponding substitution products by an S_RN1 mechanism. Competition experiments showed that the relative reactivity of chlorine as the leaving group with respect to the ester group in methyl chlorobenzoate is para ≥ ortho ? meta toward Me₃Sn^- ions. Theoretical studies were able to explain the observed reactivity on the basis of the energetic properties of the transition states of the radical anions formed in these reactions.

Full text of DOI:10.1039/b9nj00664h

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PAPER
www.rsc.org/njc | New Journal of Chemistry
Regioselectivity of methyl chlorobenzoate analogues with
trimethylstannyl anions by radical nucleophilic substitution:
theoretical and experimental study
Juan P. Montanez, Jorge G. Uranga and Ana N. Santiago*
˜
Received (in Gainesville, FL, USA) 12th November 2009, Accepted 18th January 2010
First published as an Advance Article on the web 15th March 2010
DOI: 10.1039/b9nj00664h
Reactions of methyl 2,5-dichlorobenzoate, methyl 4-chlorobenzoate, methyl 2-chlorobenzoate and
methyl 3-chlorobenzoate with Me3Snꢀ ions gave the corresponding substitution products by an
S
RN1 mechanism. Competition experiments showed that the relative reactivity of chlorine as the
leaving group with respect to the ester group in methyl chlorobenzoate is para Z ortho c meta
toward Me3Snꢀ ions. Theoretical studies were able to explain the observed reactivity on the basis
of the energetic properties of the transition states of the radical anions formed in these reactions.
The SRN1 reactions of dihaloarenes with nucleophiles
Introduction
produce either monosubstitution or disubstitution products,
depending on the substrate, the nature of the leaving group,
the nucleophile and the reaction conditions. For instance, we
have previously described the photostimulated reactions of
trimethylstannyl ions (Me3Snꢀ) with either methyl 2,5-dichloro-
benzoate (1) or methyl 3,6-dichloro-2-methoxybenzoate (2) in
liquid ammonia. These reactions produce Ar(SnMe3)2 with
very good to excellent yields (99 and 64%, respectively) by
the SRN1 mechanism.3 However, in dark conditions, 2 yields
the reduction product by HME, whereas 1 produces only the
monosubstituted product (methylchloro(trimethylstannyl)
benzoate; 3) by the SRN1 mechanism in 81% yield (eqn (5))
(Scheme 2). In this reaction, two isomers (methyl 5-chloro-2-
(trimethylstannyl)benzoate and methyl 2-chloro-5-(trimethyl-
stannyl)benzoate) might be formed. However, only one was
observed.4
The reaction of triorganostannyl ions as nucleophiles with aryl
halides has been studied extensively. The products observed in
these reactions depend on the leaving group, the nucleophile,
the solvent and on other reaction conditions, but generally
occur by halogen–metal exchange (HME) or electron transfer
(ET) mechanisms.1 Photoinitiated ET from the nucleophile is
favored among very good electron donor nucleophiles, such as
triorganostannyl ions, and also for substrates as aryl halides,
which are good electron acceptors. The reaction proceeds
through a radical nucleophilic substitution unimolecular
mechanism (SRN1), which is a chain reaction mechanism
involving radicals and radical anions (RAs) as intermediates.2
The SRN1 mechanism is shown in Scheme 1.
The isomer formed was determined through cleavage of the
trimethylstannyl group. This was carried out for methyl
chloro(trimethylstannyl)benzoate, which was stirred in
concentrated nitric acid at room temperature for 24 h.5 The
product obtained was identified as methyl m-chlorobenzoate
by NMR and compared with an authentic sample. This
product confirmed the position of chlorine in 3 and the
preferred substitution position.
Scheme 1
In the initiation step, an ET from the Nuꢀ or from a suitable
electron source to the substrate takes place, with the radical
anion (RA) of the substrate being formed as an intermediate
(eqn (1)). This RA cleaves in a subsequent step to form anꢀArꢁ
radical (eqn (2)). The Arꢁ radical can then react with Nu to
The objective of this paper is to evaluate the relative
reactivity of ortho-, meta- and para-chloro-substituted methyl
benzoate by the SRN1 mechanism, in dark and under irradiation
conditions. This reactivity was studied experimentally using
Me3Snꢀ ions as nucleophiles. In addition, theoretical calculations
give the ArNuꢀ radical anion (eqn (3)), which by ET to the
ꢁ
substrate forms the intermediates needed to continue the
propagation cycle (eqn (4)). The mechanism also involves
different termination steps depending on the nature of RX,
Nuꢀ and the experimental conditions. The overall process is a
nucleophilic substitution.
´
INFIQC, Departamento de Quımica Organica, Facultad de Ciencias
Quımicas, Universidad Nacional de Cordoba, Ciudad Universitaria,
´
´
´
´
Cordoba 5000 Argentina. E-mail: santiago@fcq.unc.edu.ar;
Fax: +54 351 4334170
Scheme 2
ꢂc
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are also reported to further understand the relative reactivity
and the reaction mechanism.
coupling with the nucleophile is faster than the reduction by
the solvent.
Relative reactivity of –Cl in ortho-, meta- and para-positions
Results and discussion
with respect to the ester group
Reactivity of methyl chlorobenzoate
To compare the reactivity of these compounds, their relative
reactivity was studied by competition experiments.6 In these
experiments, the relative reactivity depended on the rate of ET
from any of the substitution product RA intermediates to the
substrates. From these competition reactions, 4 was 1.16 times
more reactive than 5 toward Me3Snꢀ ions in the dark (Table 2,
expts. 1–3). In the same way, the dark relative reactivity of 5
was much higher than that of 6 (Table 2, expts. 4 and 5).
In photostimulated reactions, the relative reactivity of 5 was
19.3 times higher than that of 6 toward Me3Snꢀ ions (Table 2,
expt. 6).
Methyl 4-chlorobenzoate (4) and Me3Snꢀ ions reacted in the
dark, giving methyl 4-(trimethylstannyl)benzoate (7a; 32%) in
liquid ammonia. This reaction was catalyzed by light (eqn (6);
Scheme 3) and inhibited by well known inhibitors of SRN1
reactions2 (Table 1, expts. 1–4).
In the same way, methyl 2-chlorobenzoate (5) and Me3Snꢀ
ions reacted in the dark or under photostimulation, producing
methyl 2-(trimethylstannyl)benzoate (7b; 24 and 54%,
respectively) in liquid ammonia (Table 1, expts. 5–6) (eqn (6)).
By way of contrast, methyl 3-chlorobenzoate (6) failed to react
with Me3Snꢀ ions in liquid ammonia in the dark. However,
it reacted under photostimulation to give 35% methyl
3-(trimethylstannyl) benzoate (7c) (Table 1, expts. 7 and 8).
In the absence of the nucleophile (Me3Snꢀ) methyl chloro-
benzoates reacted in the dark to produce chlorobenzamide
(40–50%) in liquid ammonia. This product, however, was not
observed in the presence of the nucleophile.
As seen in Table 2, we found that the relative reactivity of
the methyl chlorobenzoate isomers was para Z ortho c meta.
These results are in agreement with data reported on similar
compounds. Tanner et al. found that the rate constant for the
fragmentation of haloacetophenone RAs was greater for
para- and ortho- compared to meta-isomers.7 For example,
they found that cleavage of the m-chloroacetophenone RA
was observed to be 420 times slower than that of its
para-isomer.
The fact that these reactions are catalyzed by light, that the
substitution products are formed and that the photostimulated
reactions are inhibited by well-known radical scavengers
suggests that these reactions occur by the SRN1 mechanism,
as shown in Scheme 4. When methyl chlorobenzoate receives
one electron, a p-RA, 8ꢁꢀ, is formed (eqn (7)). This RA gives
radical 9ꢁ by fragmentation of the C–Cl bond (eqn (8)), whicꢀh
by reaction with the nucleophile gives a new RA, 10ꢁ
(eqn (9)). This iꢀntermediate finally affords the substitution
products and 8ꢁ (eqn (10)), which can continue the chain
propagation steps.
These experimental results may explain the reactivity found
with substrate 1 under the same conditions. In the dark
reaction of 1 with Me3Snꢀ ions, two isomers might be formed:
Very low yields of the reduction product (methyl benzoate)
were found, indicating that when radical 9ꢁ is formed, the
Scheme 3
Scheme 4
Table 1 Reactions of methyl chlorobenzoates with Me3Snꢀ ions in liquid ammonia
Expt.
Substrate, M ꢃ 10ꢀ3
Nucleophile M ꢃ 10ꢀ3
Conditions (min)
Yields of product,a (substrate recovered)b
1
2
3
4
5
6
7
8
4, 4.0
4, 4.0
4, 4.0
4, 4.0
5, 4.0
5, 4.0
6, 4.0
6, 4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
NH3, dark (60)
NH3, hn (60)
7a, 32 (61)
7a, 74 (—)
7a, 21 (48)d
7a, — (88)
7b, 24 (66)
7b, 54f (18)
7c, — (100)
7c, 35g (34)
NH3, dark (60)c
NH3, dark (60)e
NH3, dark (60)
NH3, hn (60)
NH3, dark (60)
NH3, hn (60)
a
b
c
Quantified by GLC and the internal standard method, with p-dibromobenzene as a reference. Recovered and quantified as acid. With 10% p-
d
DNB added. Together with 20% substrate recovered as ester. Di-tert-butyl nitroxide (17 mol%) was added. Together with 5% methyl
g
benzoate. Together with 10% methyl benzoate.
e
f
ꢂc
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Table 2 Competition experiments of 4 vs. 5 and 5 vs. 6 with Me3Snꢀ ionsa
Expt.
Substrates, M ꢃ 10ꢀ3
Me3Snꢀ M ꢃ 10ꢀ3
Yield of products (%)a
Relation
7a
23
35
21
7b
1b
2b
3b
4, 4.0
4, 4.0
4, 4.0
5, 4.0
5, 4.0
5, 4.0
4.0
4.0
4.0
19
33
19
1.24
1.09
1.12
k4/k5 = 1.16 ꢄ 0.08 (average)
7b
49
54
80
7c
—
—
8
4b
5b
6c
5, 4.0
5, 4.0
5, 4.0
6, 4.0
6, 4.0
6, 4.0
4.0
4.0
4.0
k5 c k6
k5 c k6
k5/k6 = 19.3
a
The relation quantified by GLC and the internal standard method, with p-dibromobenzene as the reference and considering the concentration of
the substitution product formed ([substrate]t = [substrate]o ꢀ [substitution product]) (the relative reactivity of 4 vs. 5 was not calculated under
b
irradiation since reduction product (methyl benzoate) was formed). In the dark for 60 min. Irradiation time 60 min.
c
3 (ortho-substitution) or methyl 2-chloro-5-(trimethylstannyl)-
benzoate (meta-substitution); however only 3 was produced in
81% yield.4 This product was formed due to the ortho-
substitution being much faster than the meta-substitution. In
other words, the intramolecular ET (intra-ET) to chlorine in
the ortho-position was faster than the intra-ET to chlorine in
the meta-position.
The spin distribution calculated can also give an indication
of a more facile dissociation for RA intermediates. It has been
shown that the nodal properties of the MO that hosts the
unpaired electron and the spin density distribution are relevant
factors for the cleavage of RAs.10 The spin density of RAs 1, 4,
5 and 6 is shown in Fig. 1B. It is easy to see that the ester group
determines the spin distribution for the whole family of
compounds, which is always higher in its para-position, with
a nodal spin density at its meta-positions. These spin density
distributions indicate that the cleavage of RAs could be
facilitated in the ortho- and para-derivates.
Geometric and stereoelectronic parameters
To further understand the experimental results, we also carried
out theoretical calculations by employing the B3LYP
functional at the 6-31+G* level. Optimized geometries for
The potential energy surfaces (PES) evaluated for the
dissociation of RAs of 4–6 are presented in Fig. 2. To our
knowledge, this is the first time that it has been possible
to locate the transition states for the intra-ET in these
compounds. We also found and characterized the corresponding
s* RA minima as well, which were not reported in previous
studies.10 As can be clearly seen in Fig. 2 and Table 3, the
ortho- and para-isomers have comparable activation barriers
for the intra-ET. However, the relative stability of the s RAs
are clearly different, with the ortho-substituted compound (5)
showing similar stability for the s and p RAs, whereas for
compound 4, the p RA is the more stable.
ꢀ
RAs 1, 4, 5 and 6 (Fig. 1A) were obtained. Compounds 5ꢁ
and 1ꢁ showed an in-plane distortion from the optimal sp2
ꢀ
Cl–C2–C1 angle (1201) that is not typical of ortho-substituted
radical anions. These angles are 122.5 and 122.61 respectively,
most certainly due to steric repulsion with the ester group.
This distortion could facilitate the fragmentation of the ortho
position and, to our knowledge, has never been observed in
other haloaromatic RAs. Pierini et al. demonstrated that out
of plane distortions of geometry favoured the cleavage of
ortho-substituted haloaromatic RAs.8,9 However, the repulsive
interaction previously reported (out of plane) is quite different
from those observed here (in-plane).
The energies, geometries and thermodynamic parameters
evaluated for the RA intermediates in these reactions are
shown in Table 3. The methyl chlorobenzoates (4–6) presented
in the table had similar electron affinities, thus making their
single-electron reduction equally feasible. However, as shown
in Table 3, similar activation energies for the intra-ET pro-
cesses were found for 4 (3.97 kcal molꢀ1), 5 (3.30 kcal molꢀ1
)
and 1 (in C2, 4.63 kcal molꢀ1), whereas much larger activation
energies for 6 (10.22 kcal molꢀ1) and 1 (in C5, 10.64 kcal
molꢀ1) were obtained, suggesting that the meta fragmentation
is slower, in excellent agreement with the experiments. Alter-
ꢀ
natively, 6ꢁ has the lowest spin density at Cipso (the carbon
bonded to Cl) on its leaving group and is also the isomer
showing the largest activation energy. Consequently, one
could use the spin distribution to predict the relative reactivity
of the isomers.
The difference in energy between the p and s states (DEps
)
in the RAs is also shown in Table 3. As can be seen, this energy
difference is not a good indicator of reactivity since it would
predict the ortho to be the most reactive isomer. As a result, we
propose that this parameter cannot be used to determine the
Fig. 1 Geometry and unpaired spin distribution of radical anions 1,
4, 5 and 6.
ꢂc
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Table 4 Thermodynamic and kinetic parameters of the anionic
surface with solventa
E#
DEfrag
ꢀEAc
b
IEFPCM
1
C2
C5
3.30
8.85
1.51
2.38
7.45
ꢀ1.53
ꢀ9.03
ꢀ1.40
ꢀ2.01
ꢀ1.31
ꢀ56.49
4
5
6
ꢀ51.27
ꢀ51.84
ꢀ52.50
a
b
Solution phase calculation with acetonitrile as the solvent. DEfrag
(RX - Rꢁ + Xꢀ) in kcal molꢀ1
. .
DE (RX - RXꢁꢀ) in kcal molꢀ1
c
Fig. 2 UB3LYP/6-31+G* gas phase anionic profiles of methyl
chlorobenzoates 4ꢁ–6ꢁ. The neutral molecules were taken as zero
energy.
reactivity order in this type of compound, as proposed
previously.9
In addition, the solvent’s effect was evaluated by single point
calculations using acetonitrile as the solvent by means of
Tomasi’s polarizable continuum model implemented in Gaussian
(IEFPCM) (Table 4).11 When the solvent was included, the
stabilization of the s species increased, making the intra-ET
for all compounds substantially more exothermic. In addition,
including the condensed phase effect, the s RAs disappeared,
i.e. the minimum vanished and the potential energy surface
became repulsive. The activation energies predict a reactivity
order in solution of para Z ortho c meta, as can be seen in
Table 4, which is in full agreement with the experimental
trend.
Fig. 3 UB3LYP/6-31+G* anionic profiles for compound 1 (blue =
fragmentation in the ortho-position, green = fragmentation in the
meta-position). In all cases, zero energy corresponds to the neutral
compounds.
meta fragmentations; Fig. 4A shows the spin density. As can
be seen from the molecular electrostatic potential (MEP),
the initial p RA has a negative charge on the ester group,
with it gradually transferring to the Cl atom in the transition
states. A similar behavior was observed for the spin densities,
where the s radical character was formed at the transition
state’s geometry. For the ortho fragmentation it is possible
to visualize the larger electrostatic repulsion between the
chlorine atom and the ester oxygen, denoted as the red zone
in that region of the MEP. On the other hand, this repulsive
effect triggered a bigger distortion from planarity at the
transition state geometry than that observed in the meta
isomer.
The intra-ET profiles for the fragmentation of 1 in the gas
phase are presented in Fig. 3. The figure shows the anionic
profiles for the two possible fragmentations (ortho and meta)
of the p RA 1ꢁꢀ and the orbital nature of these intermediates,
represented as their SOMOs. The PES topologies of 1 for
the two possible fragmentations are similar to the above-
mentioned ones for 5 and 6. These results show that the ortho
fragmentation has substantially lower activation energy than
the meta fragmentation, which is in excellent agreement with
the experiments.
ꢀ
Fig. 4B shows the electrostatic potential at the p RA 1ꢁ
and the p–s* crossing zone (transition state) for the ortho and
Table 3 The main geometric, thermodynamic and kinetic parameters of radicals and RA intermediatesa
Compound
Gas phase
1
pRA
TS
s*RA
Cl–Cd
Anglee
Cl–Cd
Anglee
Cl–Cd
Anglee
b
DEps
E#
DEfrag
ꢀEAc
ꢀ15.37
C2
C5
1.786
1.793
1.784
1.796
1.800
180
180
180
180
180
2.031
2.107
2.140
1.997
2.149
138.95
149.18
138.75
141.08
154.35
2.531
2.585
2.519
2.631
2.691
137.43
155.32
145.46
139.84
179.76
3.13
7.79
3.64
0.57
6.59
4.63
131.28
136.81
131.25
124.29
131.87
10.64
3.97
3.30
4
5
6
ꢀ8.34
ꢀ7.87
ꢀ9.56
10.22
a
b
The zero-point energy corrections were made at the 6-31+G* level. In all cases, zero energy corresponded to the neutral compounds. DEfrag
(RX - Rꢁ + Xꢀ) in kcal molꢀ1
.
Cl–Cipso–Ca–Ca in degrees, where Ca and Ca are neighbours of Cipso
EA (adiabatic electron affinity) DE (RX - RXꢁꢀ) in kcal molꢀ1
.
c
d
e
Distance Cl–Cipso in A. Dihedral angle
0
0 0
.
ꢂc
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6.4 mmol of t-BuOK dissolved in 25 mL of dry DMSO. Then,
the reaction was quenched with 1.14 mL, 6.4 mmol of
methyl iodide. The solution was dissolved with water and then
extracted with diethyl ether. Methyl 2-chlorobenzoate (5) was
isolated as yellow oil and identified by GC-MS using the NIST
Mass Spec. Data.12
Typical procedure by SRN1 reactions photostimulated reactions
of methyl 4-chlorobenzoate (4) with Me3Snꢀ ions in liquid
ammonia
The following procedure is representative of these reactions.
Me3SnCl (1.2 mmol) and Na metal (2.4 mmol) were added to
250 mL of distilled ammonia. Na was added slowly in small
pieces until total decoloration occurred. Then, 20 min after the
last addition, when no more solid was present, the Me3Snꢀ
ions were ready for use (a lemon yellow solution). Substrate 4
(1 mmol) was added to the solution and the reaction mixture
irradiated for 1 h. The reaction was then quenched with an
excess of ammonium nitrate, and the ammonia allowed to
evaporate. The solid was dissolved in water, and HNO3 was
added to the water phase up to pH 7. The water phase
was then extracted with chloroform (phase one), and HNO3 was
added to the water phase up to pH 3 before being extracted
with chloroform (phase two). The products from chloroform
Fig. 4 Spin density (A) and electꢀrostatic potential (B) (from blue =
positive to red = negative) on 1ꢁ or the indicated points along the
reaction path for the ortho and meta fragmentations.
phase one were isolated by Kugelrohr distillation. In the other
¨
3. Conclusions
experiments, the products were quantified by GLC using
the internal standard method. The acid derivatizes from
chloroform phase two were also quantified.
We reported the reactivity and theoretical calculations of
methyl chlorobenzoates (para, ortho and meta) and methyl
2,5-dichlorobenzoate with Me3Snꢀ ions through a SRN1 reaction
mechanism. In these conditions, the compounds gave the
corresponding substitution product and the reactions were
catalyzed by irradiation. The relative reactivity of chlorine
as the leaving group with respect to the ester group in
methyl chlorobenzoates was para Z ortho c meta. Based
on calculations including solvents effects, the activation
energies obtained for the fragmentation process reproduce
the observed experimental reactivity trend.
Dark reactions with Me3Snꢀ ions in liquid ammonia
This procedure was similar to that for the previous reaction,
except that the reaction flask was wrapped with aluminium foil.
Inhibited reactions with Me3Snꢀ ions in liquid ammonia
This procedure was similar to that for the previous reaction,
except that 10 mol% of either p-DNB or di-tert-butylnitroxide
was added to the solution of nucleophile prior to substrate
addition.
4. Experimental
Isolation and identification of products
General methods
Methyl 4-chlorobenzoate (4). This was isolated as a white
solid after being extraction with diethyl ether–water. (EI+)
m/z (%): 172 (10), 170 (30), 141 (9), 140 (9), 139 (100), 113
(13), 111 (36), 75 (26), 74 (8), 63 (1), 50 (11). Mp: 43–45 1C
(lit.13 43.5 1C).
Irradiation was conducted in a reactor equipped with two 400 W
UV lamps emitting maximally at 350 nm (Philips Model HPT,
water-refrigerated). The HRMS were recorded at UCR Mass
Spectrometry Facility, University of California, United States.
Methyl 2-chlorobenzoate (5). This was isolated as yellow oil
after being extraction with diethyl ether–water. EM (EI+) m/z
(%): 172 (10), 170 (28), 141 (33), 140 (8), 139 (100), 113 (11),
111 (32), 75 (25), 74 (7), 63 (1), 50 (11).
Materials
Methyl 2,5-dichlorobenzoate (1), 4-chlorobenzoic acid,
2-chlorobenzoic acid, methyl 3-chlorobenzoate (6) and
Me3SnCl were commercially available and used as received.
Liquid ammonia was distilled under nitrogen and metallic Na,
and used immediately.
Methyl 4-(trimethylstannyl)benzoate (7a). This was isolated
as amber liquid after Kugelrohr distillation (50 1C/1mmHg).
¨
(EI+) m/z (%): 289 (17), 287 (169), 286 (10), 285 (100), 284
(33), 283 (74), 282 (26), 281 (46), 255 (33), 254 (11), 253 (23),
252 (8), 251 (13). 1H-NMR (400.16 MHz, CDCl3) d: 0.34 (9H,
s, JH–Sn = 27.4 Hz); 3.94 (3H, s); 7.50–7.70 (2H, d); 7.96–8.06
(2H, d). 13C-NMR (CDCl3) d: ꢀ9.5; 52.4; 128.4; 128.6; 129.8;
Typical procedure for reactions of esterification. preparation of
methyl 2-chlorobenzoate (5)
The following procedure is representative of these reactions.
2-Chlorobenzoic acid (1 g, 6.4 mmol) was added to 0.71 g,
ꢂc
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135.8; 149.6; 167.4. HRMS [MH]+ calc. for C11H17O2Sn
301.0245, found: 301.0249.
and W. Y. Su, Organometallics, 1984, 3, 1718–1727; J. San
Filippo Jr. and J. Silbermann, J. Am. Chem. Soc., 1981, 103,
5588–5590.
2 R. A. Rossi, A. B. Pierini and A. B. Pene
2003, 103, 71–167; R. A. Rossi, A. B. Pene
stimulated RN1 Process: Reaction of Haloarenes with
´
nory, Chem. Rev.,
Methyl 2-(trimethylstannyl)benzoate (7b). This was isolated
´
nory, The Photo-
as an amber liquid after Kugelrohr distillation (50 1C/1mmHg).
¨
(EI+) m/z (%): 289 (16), 287 (13), 286 (8), 285 (100), 284 (20),
S
Carbanions, in CRC Handbook of Organic Photochemistry
and Photobiology, ed. W. M. Horspool and F. Lenel, CRC
Press, Boca Raton, USA, 2nd edn, 2004, pp. 47; R. A. Rossi,
Photoinduced Aromatic Nucleophilic Substitution Reactions, in
Synthetic Organic Photochemistry, ed. A. G. Griesbeck and
J. Mattay, Marcel Dekker, New York, 2005, pp. 495–527.
3 A. N. Santiago, S. M. Basso, J. P. Montanez and R. A. Rossi,
J. Phys. Org. Chem., 2006, 19, 829–835.
4 S. M. Basso, J. P. Montanez and A. N. Santiago, Lett. Org. Chem.,
2008, 5, 633–639.
5 R. K. Ingham, S. D. Rosenberg and H. Gilman, Chem. Rev., 1960,
60, 459–539.
6 The equation used in the relative reactivity determination of pairs
283 (69), 282 (24), 281 (42), 255 (55), 254 (11), 253 (38), 251
1
(23). H-NMR (400.16 MHz, CDCl3) d: 0.31 (9H, s, JH–Sn
=
27.4 Hz); 3.95 (3H, s); 7.40–7.48 (1H, t); 7.51–7.60 (1H, t);
7.64–7.80 (1H, d); 8.11–8.20 (1H, d); 13C-NMR (CDCl3) d:
ꢀ7.4; 52.3; 128.3; 129.9; 131.9; 135.8; 136.5; 146.9; 168.9. HRMS
[MH]+ calc. for C11H17O2Sn 301.0245, found: 301.0236.
Methyl 3-(trimethylstannanyl)benzoate (7c). This was
isolated as an amber liquid after Kugelrohr distillation
¨
(50 1C/1mmHg). EM (EI+) m/z (%): 289 (18), 287 (14), 286
(10), 285 (100), 284 (30), 283 (74), 282 (26), 281 (43), 255 (24),
254 (6), 253 (171), 251 (10). 1H-NMR (400.16 MHz, CDCl3) d:
0.34 (9H, s, JH–Sn = 27.4 Hz); 3.94 (3H, s); 7.39–7.45 (1H, t);
7.60–7.80 (1H, d); 7.95–8.05 (1H, d); 8.10–8.30 (1H, s);
13C-NMR (CDCl3) d: ꢀ9.4; 52.0; 127.8; 129.4; 129.5; 136.7;
140.3; 142.8; 167.5. HRMS [MH]+ calc. for C11H17O2Sn
301.0245, found: 301.0253.
of substrate vs. nucleophile was: k4/k5
= ln([substrate 4]0/
[substrate 4]t)/ln([substrate 5]0/[substrate 5]t), where [substrate 4]0
and [substrate 5]0 are initial concentrations and [substrate 4]t and
[substrate 5]t are concentrations at time t of both substrates,
see: J. F. Bunnett, in Investigation of Rates and Mechanisms of
Reactions, ed. E. S. Lewis, Wiley-Interscience, New York, 3rd edn,
1974, part 1, pp. 159.
7 D. D. Tanner, J. J. Chen, L. Chen and C. Luelo, J. Am. Chem.
Soc., 1991, 113, 8074–8881.
8 A. B. Pierini, J. S. Duca and M. A. Vera, J. Chem. Soc., Perkin
Trans. 2, 1999, 1003–1009.
Methyl 5-chloro-2-(trimethylstannanyl)benzoate (3). This
9 A. B. Pierini and J. S. Duca, J. Chem. Soc., Perkin Trans. 2, 1995,
1821–1828.
10 A. B. Pierini and D. M. A. Vera, J. Org. Chem., 2003, 68,
9191–9199.
11 D. M. Chipman, J. Chem. Phys., 2000, 112, 5558–5565;
M. T. Cances, B. Mennucci and J. Tomasi, J. Chem. Phys., 1997,
107, 3032–3041.
12 Mass Spectra, in NIST Chemistry WebBook, NIST Standard
Reference Database Number 69, ed. P. J. Linstrom and W. G.
Mallard, March 2003, National Institute of Standards and
Technology, Gaithersburg MD, 20899, USA (http://webbook.
nist.gov).
was isolated as a yellow oil after Kugelrohr distillation
¨
1
(50 1C/1mmHg). H-NMR (CDCl3) d: 0.27 (9H, s, JH–Sn
=
27 Hz); 3.92 (3H, s); 7.49–7.61 (2H, m); 8.08–8.09 (1H, d).
13C-NMR (CDCl3) d: ꢀ7.4; 52.5; 129.8; 131.79; 137.7; 167.8.
EM (EI+) m/z (%): 319 (100), 317 (73), 302 (4), 289 (50), 287
(36), 272 (3), 261(6), 259 (14), 231 (5), 165 (2), 151 (24), 133 (7),
118 (5), 89 (5), 75 (7), 63 (4). HRMS (CI) exact mass calc. for
the C11H15ClO2Sn (M+ ꢀ CH3) 318.9548, found (M+ ꢀ CH3)
318.9553.
13 CRC Handbook of Chemistry and Physics 78th edition, CRC Press
Inc., Boca Raton, USA, 1997.
Computational procedures
All calculations were carried out with DFT14 methods, as
implemented in the Gaussian 03 package,15 by employing the
B3LYP16 functional at the 6-31+G* level of theory. This basis
set is known to be appropriate for the theoretical study of the
electronic and geometric properties of RAs.17 Stationary
points were characterized by the normal analysis and obtained
with complete geometry optimization without symmetry
restrictions. Potential energy surfaces (PES) were obtained
by varying the C–Cl bond length, and the B3LYP spin
contamination along the whole fragmentation path was
negligible (hS2i = 0.750–0.751). The solvation effect was
included by using a continuous model in acetonitrile solvent.
14 W. Kohn and I. Sham, Phys. Rev., 1965, 140, A1133–A1138.
15 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr.,
T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam,
S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi,
G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada,
M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida,
T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li,
J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo,
J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev,
A. J. Austin, R. Cammi, C. Pomelli, J. Ochterski, P. Y. Ayala,
K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg,
V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain,
O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari,
J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford,
J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz,
I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham,
C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill,
B. G. Johnson, W. Chen, M. W. Wong, C. Gonzalez and
J. A. Pople, GAUSSIAN 03 (Revision B.02), Gaussian, Inc.,
Wallingford, CT, 2004.
Acknowledgements
This work was supported in part by ACC, CONICET,
SECYT and ANPCyT. J. P. M. and J. G. U. gratefully
acknowledge receipt of fellowships from CONICET.
16 C. Lee, W. Yang and R. G. Parr, Phys. Rev. B: Condens.
Matter, 1988, 37, 785–789; A. D. Becke, Phys. Rev. A: At.,
Mol., Opt. Phys., 1988, 38, 3098–3100; E. Miehlich, A.
Savin, H. Stoll and H. Preuss, Chem. Phys. Lett., 1989, 157,
200–206.
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ꢂc
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