Isomeric alkyl cation/arene complexes in the gas phase

Article abstract of DOI:10.1002/chem.200204281

The kinetics and the stereochemistry of the protonation-induced unimolecular isomerization of (S)-(+)-1-D₁-3-(p-tolyl)butane have been investigated in the gas phase in the 100-160°C range. The process leads to the almost exclusive formation of

Full text of DOI:10.1002/chem.200204281

FULL PAPER
Isomeric Alkyl Cation/Arene Complexes in the Gas Phase
Antonello Filippi,*[a] Graziella Roselli,[b] Gabriele Renzi,[b] Felice Grandinetti,[c] and
Maurizio Speranza[a]
Abstract: The kinetics and the stereo-
chemistry of the protonation-induced
unimolecular isomerization of (S)-(‡)-
1-D1-3-(p-tolyl)butane have been inves-
tigated in the gas phase in the 100
1608C range. The process leads to the
almost exclusive formation of the rele-
vant meta isomer with complete race-
mization and partial 1,2-H shift in the
migrating sec-butyl group. These results,
together with the relevant activation
parameters, point to the occurrence of
low-energy, tightly bound isomeric sec-
butyl cation/toluene complexes of de-
fined structure and stability along the
isomerization coordinate. The existence
and the h1-type structure of these low-
energy intermediate species are con-
firmed by ab initio calculations on
closely related systems at the
MP2(full)/6-311‡‡G**//HF/6-31 ‡ G**
level of theory. Their role in the relevant
energy surface clearly emerges from the
comparison of the present results with
those concerning sec-butylation of tol-
uene carried out under comparable ex-
perimental conditions.
Keywords: arenium ion isomeriza-
tion
¥
chirality
¥
electrophilic
substitution ¥ gas-phase reactions ¥
kinetics
the process. This paper is aimed at providing a novel
interpretation of the factors governing the positional selec-
tivity in a representative gas-phase electrophilic aromatic
substitution, that is the sec-butylation of toluene, based on a
careful investigation of the nature and the dynamics of the
INC involved.
Introduction
Noncovalent ion-neutral complexes (INC), first postulated in
the study of bimolecular reactions, are widely recognized as
intermediates in unimolecular isomerization and fragmenta-
3]
tion of excited ions.[1 Their occurrence in electrophilic
aromatic substitutions is nowadays supported by a variety of
refined theoretical, spectroscopic, and mass spectrometric
techniques, which provided precious information on their
Some insights into the nature and the relative stability of
the noncovalent INC structures involved in these reactions
were given by Audier and co-workers who calculated the
potential energy profiles (PES) of several arene alkylations in
the gas phase at the HF/6-31G**//HF/3-21G level of theory.[6]
According to these calculations, the INC involved in these
reactions correspond to energy minima with a loose p-
structure, where the alkyl cation and the aromatic ring lie in
quasi-parallel planes and the formally charged carbon is
centered above the ring centroid (the ™a-complex∫ in Fig-
ure 1). The stabilization energies of these a-complexes
relative to the separated components never exceed 13
15 kcalmolÀ1. The relative rotation of the two components
of the complex is partially hindered by activation barriers
from about 3 (sec-alkyl cation flipping over the arene ring) to
about 10 kcalmolÀ1 (the arene ring flipping over the sec-alkyl
cation). Instead, the INC involved in the fragmentation of the
s-bonded alkylarenium intermediates (e.g. I) to the relevant
arenium ion/alkene pair corresponds to an energy minimum
7]
lifetime.[4 However, other INC key features, such as the
mutual orientation of their components and the nature of the
forces holding them together, usually escape precise deter-
mination because of intrinsic limitations of the available
experimental methodologies.[8] This lack of information is
particularly unsatisfactory since, in principle, the nature and
the dynamics of the INC components may control their
evolution to products and, thus, determine the selectivity of
[a] Dr. A. Filippi, Prof. M. Speranza
¡
Facolta di Farmacia, Dipartimento di Studi
di Chimica e Tecnologia delle Sostanze Biologicamente Attive (No. 64)
¡
Universita degli Studi di Roma ™La Sapienza∫
P.le A. Moro 5, 00185 Roma (Italy)
Fax : (‡)0649913602
E-mail: antonello.filippi@uniroma1.it
[b] Dr. G. Roselli, Prof. G. Renzi
Dipartimento di Scienze Chimiche
‡
with an even looser p-structure held together by a C -H ¥¥¥ p
¡
Universita degli Studi di Camerino
interaction between the arenium ion and the double bond of
the alkene moiety (the ™b-complex∫ in Figure 1). No precise
information about the relative stability of the a- and b-
complexes conceivably involved in the I fragmentation was
provided. Nevertheless, following Audier×s indications,[6] the
two complexes can be considered as almost equally stable.
V. S. Agostino 1, 62032 Camerino (Mc) (Italy)
[c] Prof. F. Grandinetti
Dipartimento di Scienze Ambientali and
Instituto Nazionale di Fisica della Materia (INFM)
¡
Universita della Tuscia
¡
Largo dell'Universita, 01100 Viterbo (Italy)
2072
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/chem.200204281
Chem. Eur. J. 2003, 9, 2072 2078

2072 2078
were carried out in CH4 at
60 Torr in the presence of trace
amounts of a radical scavenger
(O2) and of a powerful base
(B ˆ (C2H5)3N). Protonation of
1S was obtained by using the
‡
strong Br˘nsted acids CnH5
(n ˆ 1,2), which can be conven-
iently generated in the gas
phase by g-radiolysis of CH4.
Experimental Section
Materials: Methane, [D4]methane,
and oxygen were high-purity gases
from UCAR Specialty Gases N.V.,
used without further purification.
Triethylamine was purchased from
ICON Services.
(S)-(‡)-1-D1-3-(p-Tolyl)butane (1S):
A solution of (S)-(‡)-3-(p-tolyl)bu-
tan-1-ol (0.2 g) (gift by C. Fuganti and
S. Serra of Politecnico di Milano)[9] in
Figure 1. Schematic potential energy-reaction coordinate diagram for the gas-phase sec-butylation of toluene.
anhydrous diethyl ether (3 mL) was
treated with sodium hydride (0.3 g).
According to the model PES of Figure 1, the positional
selectivity of gas-phase arene alkylations can be simply
related to the different activation free energies for the
conversion of the loosely-bound INC, either the a- and b-
complexes, to the isomeric s-bonded alkylarenium intermedi-
ates. This view is severely questioned in the present kinetic
investigation, based on a specifically designed experimental
approach, which provides an alternative mechanistic model
for this important class of reactions. The investigation
required the synthesis of a tailor-made chiral arylalkane, that
is (S)-(‡)-1-D1-3-(p-tolyl)butane (1S), and the measure of its
protonation-induced isomerization and dealkylation kinetics
as a function of temperature (Tˆ 100 1608C). The reactions
The mixture was stirred and heated under reflux for 6h. The suspension of
the sodium alkoxide was cooled to À208C with a dry ice bath and a solution
of p-toluenesulphonyl chloride (1.5 g) in anhydrous diethyl ether (4 mL)
was then added dropwise to the suspension. The reaction mixture was
allowed to stand in the cold for 10 min, subsequently at room temperature
for 45 min, and finally was heated under reflux for 2 h. The mixture was
washed with diluted HCl, subsequently with water and dried over Na2SO4.
The dried solution was added slowly to a suspension of LiAlD4 (0.2 g) in
anhydrous diethyl ether (4 mL). The mixture was heated under reflux for
8 h and then cooled and treated with ice-water to decompose excess of
LiAlD4. After acidification with diluted H2SO4 and extraction with diethyl
ether (20 mL Â 2), the organic extracts were washed with water, then dried
and evaporated to give (S)-(‡)-1-D1-3-(p-tolyl)butane (1S; 25 mg, ee 99%).
(Æ)-2-(p-[D7]Tolyl)butane (1D): This product was obtained by conven-
tional Friedel Crafts sec-butylation of [D8]toluene (Aldrich; D content:
97.6%) with 2-chlorobutane in the presence of aluminium chloride.[10]
Purification of the starting substrates: The synthetic products 1S and 1D
were purified by preparative gas liquid chromatography (GLC) on: i) a
5 m  4 mm (i.d.) stainless steel column packed with 10% Carbowax 20M
on 80 100 mesh Chromosorb WAW at 908C; ii) a 5 m  4 mm (i.d.)
stainless steel column packed with 10% SP-1000 on 100 120 mesh
Supelcoport at 908C. The chemical and optical purity of 1S was verified
by analytical GLC on the same chiral columns used for the analysis of its
gas-phase protonation products (MEGADEX DACTBS-b (30% 2,3-di-O-
acetyl-6-O-tert-butyldimethylsilyl-b-cyclodextrin in OV1701, 25 m long,
0.25 i.d., df ˆ 0.25 mm), 40 < T< 1308C, 28CminÀ1; CP-Chirasil-DEX CB,
25 m long, 0.25 mm i.d., df ˆ 0.25 mm), 40 < T< 1708C, 58CminÀ1).
Abstract in Italian: La cinetica e la stereochimica di isome-
rizzazione unimolecolare di (S)-(‡)-1-D1-3-(p-tolil)butano
indotta da protonazione sono state studiate in fase gassosa
nell×intervallo di temperatura da 100 a 1608C. Il processo porta
alla formazione quasi esclusiva del corrispondente isomero
meta mediante migrazione del gruppo sec-butilico accompa-
gnata dalla completa racemizzazione del centro chirale e
parziale riarrangiamento dei suoi atomi di idrogeno. Questi
risultati, insieme con i relativi parametri di attivazione,
suggeriscono che l×isomerizzazione di (S)-(‡)-1-D1-3-(p-to-
lil)butano indotta da protonazione avviene attraverso com-
Procedure: The gaseous mixtures were prepared by conventional proce-
dures with the use of a greaseless vacuum line. The starting chiral arene 1S
(or 1D), the thermal radical scavenger O2, and the base (C2H5)3N (proton
[11]
affinity (PA) ˆ 234.7 kcalmolÀ1
)
were introduced into carefully out-
plessi alchil catione/toluene isomerici a bassa energia con
gassed 130 mL Pyrex bulbs, each equipped with a break-seal tip. The bulbs
were filled with CH4 (or CD4) (60 Torr), cooled to liquid-nitrogen
temperature, and sealed off. The gaseous mixtures were submitted to
irradiation at a constant temperature (100 1608C) in a 60Co g-source
(dose: 3.4 Â 104 Gy; dose rate: 2 Â 103 GyhÀ1, determined with a neo-
pentane dosimeter). Control experiments, carried out at doses ranging from
1 Â 104 to 1 Â 105 Gy, showed that the relative yields of products are largely
independent of the dose. The radiolytic products were analysed by GLC,
with a Perkin-Elmer 8700 gas chromatograph equipped with a flame
ionisation detector, on the same columns used to check the purity of the
starting arene. The products were identified by comparison of their
1
¡
strutture e stabilita definite (complessi tipo h ). L×esistenza e la
struttura di tali complessi a bassa energia sono state confermate
dai risultati di calcoli quantomeccanici di tipo abinitio su
sistemi analoghi
a
livello MP2(full)/6-311‡‡G**//HF/6-
31‡G**. Il ruolo chiave di questi intermedi finora trascurati
emerge chiaramente dal confronto dei risultati presentati con
quelli riguardanti la sec-butilazione diretta del toluene nelle
stesse condizioni sperimentali.
Chem. Eur. J. 2003, 9, 2072 2078
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¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2073

A. Filippi et al.
FULL PAPER
retention volumes with those of authentic standard compounds and their
identity confirmed by GLC-MS, using a Hewlett Packard 5890A gas
chromatograph in line with a HP 5970B mass spectrometer. Their yields
were determined from the areas of the corresponding eluted peaks, using
an internal standard (acetophenone) and individual calibration factors to
correct for the detector response. Control experiments were carried out to
rule out the occurrence of thermal fragmentation, isomerization, and
racemization of the starting arene as well as of their isomeric products
within the temperature range investigated.
derives from its de-sec-butylation. The nature itself of the
products listed in Table 1, in particular their complete
racemization and the extensive side-chain H-shift, excludes
any significant methyl-group shift in I (path i in Scheme 1).
According to Scheme 1 and with the reasonable assumption
that deprotonation of the relevant arenium ions by (C2H5)3N
is fast, the rate constants for dealkylation (k1) and isomer-
ization (k2 and k3) of I can be expressed as follows:
The D-content and location in the radiolytic products were determined by
GLC-MS, setting the mass analyser in the selected ion mode (SIM). The ion
P
Y4 ln ‰100=ꢀ100 À †Š
‡
‡
‡
fragments at m/z 119 [M À C2H4D] , 120 [M À C2H5] , and 149 [M] were
monitored to analyse all the GLC-separated isomers of 1S (ˆ^ M). The
isomers of 1D (ˆ^ MD) were examined by using the fragments at m/z 125
k1 ˆ
k2 ˆ
k3 ˆ
(1)
(2)
(3)
P
t
P
Y2 ln ‰100=ꢀ100 À †Š
‡
‡
‡
[MD À C2H4D] , 126[ MD À C2H5] , and 155 [MD] . Toluenes 4, obtained
from 1S and 1D, were analysed by monitoring the ions at m/z 91 93 and m/z
96 100, respectively.
P
t
P
Y3 ln ‰100=ꢀ100 À †Š
Computational details: Quantum-chemical ab initio calculations were
performed using the Unix version of the Gaussian 98 set of programs[12]
installed on a Alphaserver Compaq DS20E machine. The geometries of the
investigated species have been optimised, by analytical-gradient techni-
ques, at the HF/6-31‡G** level of theory, and the located critical points
have been unambiguously characterized as true minima on the potential
energy surface by computing, at the same computational level, the
corresponding analytical vibrational frequencies. The latter values were
used to calculate the zero-point vibrational energies (ZPE). The total
energies of the HF/6-31‡G** optimised structures were finally refined by
performing single-point calculations at the MP2/6-311‡‡G** level of
theory using the ™full∫ option so to include all the inner electrons in the
calculation of the correlation energy.
P
t
where Yi (ˆ 100  [Gi/G(CnH5 )])[13] is the absolute percent
yield of i-nth product relative to the starting I, S ˆ Y2‡Y3‡Y4,
and t is the collision time between the arenium ions and B ˆ
(C2H5)3N (t ˆ (kcoll[B])À1) at the given temperature.[14]
‡
The Arrhenius plots of k1, k2, and k3 over the 100 1608C
temperature range are reported in Figure 2. The linear curves
obey the following equations: logk1 ˆ (11.4 Æ 0.5) À [(10.6 Æ
0.9) Â 103]/2.303RT
(r2 ˆ 0.993);
logk2 ˆ (12.1 Æ 0.8) À
[(11.1 Æ 1.5)  103]/2.303RT (r2 ˆ 0.983); and logk3 ˆ (15.4 Æ
1.5) À [(17.7 Æ 2.8)  103]/2.303RT (r2 ˆ 0.975). The relevant
activation parameters are calculated from the transition-state
theory equation as: DH= ˆ 9.8 Æ 0.9 kcalmolÀ1 and DS=
ˆ
Results
1
1
À8.7 Æ 2.7 calmolÀ1 KÀ1
;
DH= ˆ 10.3 Æ 1.2 kcalmolÀ1 and
2
Radiolytic experiments: Table 1 reports the composition of
the irradiated systems as well as the identity and the yields of
the major products, that is (Æ)-1-D1-3-(m-tolyl)butane (2),
(Æ)-1-D1-2-(m-tolyl)butane (3), and toluene (4), obtained
DS= ˆ À5.3 Æ 3.6calmol À1 KÀ1
;
and
DH= ˆ 16.9 Æ
2
3
3.1 kcalmolÀ1 and DS= ˆ ‡9.9 Æ 7.0 calmolÀ1 KÀ1.
3
To shed some light upon the specific mechanism of isomer-
ization of I, ancillary experiments were carried out under the
‡
‡
from gas-phase CnH5 (n ˆ 1,2) protonation of 1S in the
same experimental conditions using CnD5 (n ˆ 1,2), as a
presence of trace amounts of (C2H5)3N (0.1 Torr). The table
does not include other very minor products, that is deuterated
(Æ)-2-(o-tolyl)butane and (R)-(À)-2-(p-tolyl)butane, whose
overall yield never exceeds 3% of the reported products
under all conditions. The numbers in Table 1 represent
average values obtained from several separate irradiations
carried out under the same experimental conditions; its
reproducibility is expressed by the uncertainty level quoted.
The ionic origin of the radiolytic products is demonstrated by
the sharp decrease (over 80%) of their abundance as the
(C2H5)3N concentration is raised from about 0.1 to about
0.5 mol%.
Br˘nsted acid, and (Æ)-2-(p-[D7]tolyl)butane (1D), as the
substrate. Indeed, as pointed out by Audier and co-workers,[15]
occurrence of the b-complexes (Figure 1) in the fragmenta-
tion of deuterated 1D would lead to appreciable D/H
scrambling between the arene and the sec-butyl moieties.
‡
Gas-phase deuteration of 1D with radiolytic CnD5 yields the
same product pattern of Table 1, with the obvious difference
that 2-(m-[D7]tolyl)butane and 2-(m-[D6]tolyl)butane[16, 17] are
formed instead of 2 and 3, and [D8]toluene and [D7]tol-
uene[16, 18] are formed instead of 4. Careful mass spectrometric
analysis of these products reveals that [2-(m-[D7]tolyl)bu-
tane]/[2-(m-[D6]tolyl-butane] ˆ [[D8]toluene]/[[D7]toluene].
Besides, the 2-(m-[D7]tolyl)butane and 2-(m-[D6]tolyl)butane
products exhibit just the same deuterium content in both the
Products 2 and 3 arise from the isomerization of the ipso-
protonated intermediate I of Scheme 1, while toluene 4
Table 1. Kinetics of gas-phase isomerization and dealkylation of protonated (S)-(‡)-1-D1-3-(p-tolyl)butane 1S.
[c]
[c]
[c]
[e]
[e]
[e]
System Comp.[a]
Treaction
treaction
(t  107 s)[b]
Y2
Y3
Y4
S[d]
k1
k2
k3
1S [Torr]
[8C]
(Â10À5 s)
(Â10À5 s)
(Â10À5 s)
0.38
0.34
0.43
100
130
160
3.23
3.51
3.78
12.9
27.5
41.1
3.65.0
12.1
40.7
21.5
11.1
14.4
1.7 (5.24)
50.7
96.2
5)4.5 (5.6 1.2 (5.10)
4.4 (5.64)
12.9 (6.1)
10.9 (6.04)
36.9 (6.57)
4.8 (5.68)
36.6 (6.56)
[a] CH4: 60 Torr, O2: 10 Torr; (C2H5)3N: 0.1 Torr. Radiation dose: 3.4 Â 104 Gy (dose rate: 2 Â 103 GyhÀ1). [b] Reaction time, t, calculated from the
‡
reciprocal of the first-order collision constant between the relevant ionic adduct and (C2H5)3N (see text). [c] Yˆ 100  [G(product)/G(CnH5 )] (G values
expressed as the number of molecule of the given species per 100 eV of energy absorbed by the gaseous mixture). [d] S ˆ Y2 ‡ Y3 ‡ Y4; each value is the
average of several determinations, with an uncertainty level of ca. 5%. [e] logk in parentheses.
2074
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chem. Eur. J. 2003, 9, 2072 2078

Isomenic Alkyl Cation/Arene Complexes
2072 2078
Scheme 1.
conditions. sec-Butyl ion attack on toluene leads to the
formation of appreciable proportions of (Æ)-2-(o-tolyl)butane
and (Æ)-2-(p-tolyl)butane (43 46% overall relative yield)
besides (Æ)-2-(m-tolyl)butane (54 57%).[19] The almost
complete absence of (Æ)-2-(o-tolyl)butane and (R)-(À)-2-(p-
tolyl)butane from I isomerization (ꢁ3%) excludes that both
processes involve the intermediacy of the same noncovalent
a-complexes.
Theoretical calculations: The structure and the energetics of
the stable intermediates involved in I isomerization were
investigated by quantum-chemical ab initio calculations at the
post-SCF level of theory. In order to reduce the calculation
size, protonated sec-butyl benzene, instead of I, was consid-
ered. Exploration of the HF/6-31‡G** potential energy
surface (PES) of protonated sec-butyl benzene around con-
ceivable regions led to the location of only two distinct critical
points, unambiguously characterized as true minima by
analytical computation of the corresponding vibrational
frequencies. The connectivity and the main geometrical
parameters of these structures are shown in Figure 3 and
their absolute and relative energies at the MP2(full)/6-
311‡‡G**//HF/6-31‡G**‡ZPE(HF/6-31‡G**) collected
in Table 2.
&
*
), k2
^
Figure 2. Temperature dependence of the k1
(
(
), and k3 ( ) rate
constants concerning the I ! 4, I ! II, and I ! III reactions, respectively.
corresponding parent [MD] and [MD À ethyl] fragment ions.
These observations speak in favor of the same ionic precursor
(i.e., the deuterated analogue of I) of both ring-deuterated
2-(m-tolyl)butanes and toluenes. The same results rule out
any appreciable D/H scrambling between the aromatic ring
and the side chain of deuterated 1D during its isomerization
and dealkylation and, therefore, the intermediacy of the
noncovalent b-complex.
‡
‡
The conceivable occurrence of the noncovalent a-complex
of Figure 1 during I isomerization was ruled out by a second
set of ancillary experiments. Thus, ionic sec-butylation of
toluene was carried out at 70 Torr and in the 100 1608C
range using free sec-butyl cation as the electrophile. The
relevant product distribution has been compared with that
obtained from I isomerization carried out under identical
Discussion
Energetics: Gas-phase protonation of 1S by the strong
‡
Br˘nsted acids CnH5 (n ˆ 1,2) is an exothermic process
yielding the corresponding arenium ion protomers.[16] Forma-
Chem. Eur. J. 2003, 9, 2072 2078
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¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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A. Filippi et al.
FULL PAPER
Table 2. Computed MP2(full) absolute and relative energies (including
ZPEs) and zero-point energies (ZPE) of intermediates involved in
isomerization and fragmentation of protonated sec-butylbenzene.
these loosely bound structures do not correspond to the
noncovalent a- and b-complexes of Figure 1.
This conclusion is corroborated by the evident gap between
ZPE [kcalmolÀ1
]
DE [kcalmolÀ1
]
the measured activation enthalpies of the I ! II (DH=
ˆ
Structure
E [au]
2
10.3 Æ 1.2 kcalmolÀ1) and I ! III isomerizations (DH=
ˆ
benzene
À 231.696585
À 157.107375
À 231.982775
À 156.820785
À 388.856944
À 388.833906
67.27
77.93
74.04
72.00
149.71
146.67
3
16.9 Æ 3.1 kcalmolÀ1) and the HF/6-31G**//HF/3-21G-com-
puted enthalpy difference between I and the noncovalent a-
and b-complexes of Figure 1 (ca. 20 kcalmolÀ1). This discrep-
ancy clearly indicates that the I ! II and I ! III isomerization
reactions proceed through transition structures placed well
below the noncovalent a- and b-complexes on the relevant
PES (i.e., TS and TS' in Figure 1, respectively). The complete
racemization and the temperature-dependent 1,2-H shift
accompanying the sec-butyl group C(1) ! C(2) motion in I
provide mutually reinforcing pieces of evidence for the
presence of long-lived intermediates around the TS and TS'
transition structures which allow for several rotations and
bond vibrations in the sec-butyl moiety before s-bonding to II
or III (i.e., the X complex of Figure 1).
sec-butyl ion
benzenium ion
trans-2-butene
s-complex
28.74
29.84
0.00
11.41
h1-complex
tion of the ipso-protonated intermediate I is estimated to be
exothermic by 59 (n ˆ 1) and 26kcalmol À1 (n ˆ 2).[11] The
excess energy imparted to the ion I and the CnH4 fragments by
the exothermicity of their formation process is efficiently
dissipated by multiple unreactive collisions with the bulk CH4
gas. As illustrated in Scheme 1, the ipso-intermediate I may
isomerize to ions II and III, with complete racemization of the
sec-butyl group, or undergo de-sec-butylation to give even-
tually the products of Table 1.
With the reasonable assumption that the proton affinity
(PA) of 1S at C(1) is comparable with that of p-xylene (PA ˆ
190 kcalmolÀ1),[11] the heat of formation of I can be estimated
as 161 kcalmolÀ1. In the same way, the heat of formation of II
(and III) can be estimated as 165 kcalmolÀ1, whereas that of
VI (Figure 2) is about 158 kcalmolÀ1.[11, 16] Unimolecular
dissociation of I to give the separated toluene/sec-butyl cation
and the p-toluenium ion/2-butene pairs can be calculated to
be about 35 and 27 kcalmolÀ1 endothermic, respectively
(Figure 1).[11]
The activation parameters of the I ! II isomerization
(DH= ˆ 10.3 Æ 1.2 kcalmolÀ1
and
DS= ˆ À5.3 Æ
2
2
3.6calmol À1 KÀ1) assign to this X complex a low-energy, tight
structure, where free mutual motions of the sec-butyl group
and the toluene components is severely hampered by intense
interactions. This species is identified as the methylated
analogue of the h1-type complex of Figure 3.[20] Neighboring-
Despite the obvious structural, electronic, and temperature
differences, these values well compare with the relevant DE
values of Table 2. Both sets of dissociation energies are
consistent with the experimentally observed predominant
‡
release of the C7H9 /C4H8 pair from dissociation of I and of
the C4H9 /C6H6 one from protonated sec-butyl benzene.[5, 15]
‡
Figure 3. HF/6-31‡G**-optimized structures and main geometrical parameters
of the stable s- and h1-type complexes located on the potential energy surface
(PES) of protonated sec-butyl benzene (bond lengths in ä; angles in 8 (in italic)).
The isomerization mechanism: Having excluded any signifi-
cant occurrence of path i of Scheme 1, the formation of (Æ)-1-
D1-3-(m-tolyl)butane (2) from 1S must necessarily arise from
the I ! II isomerization involving the complete racemization
of the chiral sec-butyl moiety (path ii of Scheme 1). sec-Butyl
group racemization is accompanied by partial 1,2-H shift, as
demonstrated by the concomitant formation of (Æ)-1-D1-2-
(m-tolyl)butane (3) (path iii of Scheme 1).[5, 15] These findings
point to intermediate structures along the I ! II/III reaction
À
group effects in the sec-butyl moiety of the h1-complex may
‡
induce CHMe -group flipping so that the formally vacant
p-orbital can undergo attack on both its sides from the
adjacent ring-C(3) and -C(5) centers (path i of Scheme 2).
The activation parameters of the I ! III isomeriza-
tion
DH= ˆ 16.9 Æ 3.1 kcalmolÀ1
and
DS= ˆ ‡9.9 Æ
coordinate characterized by extensive Cring
Calkyl bond cleav-
3
3
7.0 calmolÀ1 KÀ1) point to an additional higher-energy route
age.[5, 6, 17] However, as pointed out in the Results Section,
Scheme 2.
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Isomenic Alkyl Cation/Arene Complexes
2072 2078
to the X complex, involving a comparatively looser transition
structure TS' where the interaction between the sec-butyl
group and the toluene p-system is enough weakened to allow
1,2-H shift in the sec-butyl moiety (path ii of Scheme 2). The
1,2-H shift in the sec-butyl moiety may allow attack from the
adjacent ring-C(3) centers with formation of III. The isomer-
ization sequences, proposed in Scheme 2, account for all the
experimental findings, including the lack of any significant
formation of both (Æ)-2-(o-tolyl)butane and (R)-(-)-2-(p-
tolyl)butane from protonation of 1S. The h1-type X complexes
involved in the isomerization pathways are characterized by
defined structure and stability arising from the spatial
meta: 30%; para: 28%).[19] When the pressure is lowered to
70 Torr at the same temperature, a considerable change in the
isomeric distribution of the alkylated products (ortho: 35%;
meta: 47%; para: 18%) is observed, which is attributed to a
facile interconversion among the isomeric s-bonded arenium
ions.
The present study on the gas-phase isomerization of I
indicates that these arenium ions are long lived at 70 Torr and
within the 100 1608C range. Indeed, the I ! II isomerization
rate constants measured within this temperature range (k2 ˆ
4.5 Â 105 sÀ1 (at 1008C); 1.1 Â 106 sÀ1 (at 1608C); Table 1)
indicate that I undergoes from about 1600 (1608C) to about
4000 (1008C) collisions with CH4 before isomerizing to II.[22]
Thus, at 70 Torr and Tꢁ 1608C, the I arenium ion lives long
enough to be in thermal equilibrium with the bulk gas before
reacting. The same conclusion is valid a fortiori when isomeric
s-bonded arenium ions are generated by sec-butylation of
toluene at room temperature and in the 70 710 pressure
range.[19] Accordingly, the relative population of these ions
should depend only on the temperature and not on the bulk
gas pressure.
‡
relationship between the specific Carom ¥¥¥ C interaction and
the ring substituent group. In this view, the sec-butyl ion/
toluene potential energy surface can be characterized by the
intermediacy of isomeric para, meta, and ortho h1-type
complexes, which may control the subsequent formation of
the corresponding s-intermediates and, hence, determine the
positional selectivity of the process (see below).[21]
The dealkylation mechanism: According to Figure 1, the
energy required for the unimolecular de-sec-butylation of I
(27 kcalmolÀ1) largely exceeds the activation enthalpy meas-
The large pressure effect on the isomeric distribution of
products from gas-phase sec-butylation of toluene (Tˆ
248C)[19] can find a rationale only by acknowledging the
intermediacy of isomeric h1-type complexes with lifetimes
comparable with their collision time with the bulk gas at 70
710 Torr (5 Â 10À10 5 Â 10À11 s).[14, 23]
ured for the formation of toluene 4 from I (DH= ˆ 9.8 Æ
1
0.9 kcalmolÀ1). This discrepancy, coupled with the negative
activation entropy value (DS= ˆ À 8.7 Æ 2.7 calmolÀ1 KÀ1),
1
excludes any conceivable unimolecular I fragmentation to 4,
while supporting the direct formation of toluene by the
exothermic bimolecular b-elimination process induced by
In this frame, the positional selectivity of the gas-phase sec-
butylation of toluene, a model reaction for electrophilic
aromatic substitutions, is determined by the relative popula-
tion of isomeric h1-type complexes and the activation free
energies for their conversion to the relevant s-bonded
arenium ions. When collisional cooling of the h1-type com-
plexes is efficient (high pressure), the reaction is essentially
controlled by enthalpy factors favoring the formation of their
ortho and para isomers and their conversion to the corre-
sponding s-arenium intermediates. When instead collisional
cooling of the h1-type complexes is not so efficient (low
pressure), their relative population and conversion to the
corresponding s-arenium ion can be significantly altered by
the contribution of the entropic factors.
(C2H5)3N attack at the side chain of
À20.6kcalmol À1).[11]
I
(DHelim
ˆ
Comparison with the gas-phase sec-butyl cation attack on
toluene: Formation of the tightly-bound h1-type complexes in
the isomerization of I (Scheme 2) rises some questions about
the role of these intermediates in determining the substrate
and positional selectivity of the gas-phase ionic alkylation of
arenes. Whichever alkylation route is considered, either by
attack of the alkyl cation on the arene or by addition of the
arenium ion on the alkene, the classical mechanistic model
involves the preliminary formation of a loosely-bound INC,
either the a- and b-complex (Figure 1), acting as a micro-
scopic reaction ™vessel∫ wherein the reactants are confined by
electrostatic forces. According to this model, the a- and b-
complexes may easily equilibrate if separated by a low
activation barrier. The substrate selectivity of the alkylation
reaction essentially reflects the competition between the
collisional stabilization of the loosely-bound INC and their
fragmentation. The positional selectivity reflects instead the
different activation free energies for the conversion of the
loosely-bound INC to the isomeric s-bonded arenium struc-
tures.
Acknowledgement
The financial support from the Universities of Rome ™La Sapienza∫ and
Camerino and the Italian National Research Council (CNR) is gratefully
acknowledged. The authors wish to express their gratitude to C. Fuganti
and S. Serra (Politecnico di Milano) for a kind gift of (S)-(‡)-3-(p-
tolyl)butan-1-ol, and to F. Cacace for critically reading the manuscript.
[1] T. Su, M. T. Bowers, Int. J. Mass Spectrom. Ion Phys. 1973, 12, 347.
[2] T. Su, M. T. Bowers, Gas-Phase Ion Chemistry (Ed.: M. T. Bowers),
Academic Press, New York, 1979, p. 83.
[3] T. F. Magnera, P. Kebarle, Ionic Processes in the Gas Phase (Ed.:
M. A. Almoster-Ferreira), Reidel, Dordrecht, 1984, p. 135.
[4] a) M. J. S. Dewar, The Electronic Theory of Organic Chemistry,
Oxford University Press, London, 1949; b) R. D. Bowen, Acc. Chem.
Res. 1991, 24, 364; c) P. Longevialle, Mass Spectrom. Rev. 1992, 11, 157;
d) T. H. Morton, Org. Mass Spectrom. 1992, 16, 423; e) S. Fornarini,
A careful comparison of the present experimental results
with those from the direct sec-butylation of toluene seems to
put into question this widely accepted model. Indeed, at 248C,
the positional selectivity of the sec-butyl cation toward
toluene is thought to be represented most faithfully by the
relative population of the isomeric s-bonded arenium ions,
measured at the highest pressures (710 Torr; ortho: 42%;
Chem. Eur. J. 2003, 9, 2072 2078
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¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2077

A. Filippi et al.
FULL PAPER
M. E. Crestoni, Acc. Chem. Res. 1998, 31, 827; f) D. Kuck, Int. J. Mass
Spectrom. 2002, 213, 101.
[5] R. H. Holman, M. L. Gross, J. Am. Chem. Soc. 1989, 111, 3560, and
references therein.
mixture together with its bulk component or formed from its
radiolysis. As pointed out previously (A. Troiani, F. Gasparrini, F.
Grandinetti, M. Speranza, J. Am. Chem. Soc. 1997, 119, 4525; M.
Speranza, A. Troiani, J. Org. Chem. 1998, 63, 1020), the average
stationary concentration of H2O in the radiolytic systems is estimated
to approach ca. 2 3 Torr. Therefore, it is conceivable that most of the
¬
[6] D. Berthomieu, V. Brenner, G. Ohanessian, J. P. Denhez, P. Millie,
H. E. Audier, J. Phys. Chem. 1995, 99, 712, and references therein.
‡
‡
¡
[7] M. Aschi, M. Attina, F. Cacace, Chem. Eur. J. 1998, 4, 1535, and
CnH5 will collide with water to give H3O before reacting with the
‡
references therein.
[8] See, however: M. Aschi, A. Troiani, F. Cacace, Angew. Chem. 1997,
109, 116; Angew. Chem. Int. Ed. Engl. 1997, 36, 83.
aromatic substrate. The formed H3O are stable enough to eventually
protonate 1S exothermically (DHprot ˆ À24 kcalmolÀ1).
[17] J. P. Denhez, H. E. Audier, D. Berthomieu, Org. Mass Spectrom. 1993,
28, 704.
[9] C. Fuganti, S. Serra, A. Duilio, J. Chem. Soc. Perkin Trans. 1 1999, 279.
[10] B. S. Furniss, A. J. Hannaford, P. W. G. Smith, A. R. Tatchell, Vogel×s
Textbook of Practical Organic Chemistry, Longman Scientific &
Technical, Harlow Essex (England), Chapter 6, pp. 828 833.
[11] See: http://webbook.nist.gov/chemistry/
[12] Gaussian 98, Revision A7, M. J. Frish, G. W. Trucks, H. B: Schlegel,
G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A.
Montgomery, Jr., R. E. Stratman, J. C. Burant, S. Dapprich, J. M.
Millam, A. D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi,
V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo,
S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui, K.
Morokuma, D. K. Malik, A. D. Rabuck, K. Raghavachari, J. B.
Foresman, J. Cioslowski, J. V. Ortiz, A. G. Raboul, B. B. Stefaniv, G.
Liu, A. Liashenko, P. Piskorz, I. Nanayakkara, C. Gonzales, M.
Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, J. L.
Andres, C. Gonzales, M. Head-Gordon, E. S. Replogle, J. A. Pople,
Gaussian, Inc., Pittsburg, PA, 1998.
[18] The presence of ubiquitous water in the irradiated systems induces
partial H/D exchange with the ring deuteriums of deuterated 1D (J. Ni,
A. G. Harrison, Can. J. Chem. 1995, 73, 1779).
[19] F. Cacace, G. Ciranni, P. Giacomello, J. Am. Chem. Soc. 1981, 103,
1513.
[20] W. B. Smith, J. Phys. Org. Chem. 2002, 15, 347, and references therein;
see also: D. Heidrich, Angew. Chem. 2002, 114, 3343; Angew. Chem.
Int. Ed. 2002, 41, 3208.
[21] The almost exclusive I ! II and I ! III isomerizations can be
considered as positionally ™troposelective∫ in a broad sense (A.
Filippi, M. Speranza, J. Am. Chem. Soc. 2001, 123, 6077), since the
selectivity of the moving sec-butyl group for the meta ring carbon is
determined by its original spatial location (the para ring carbon).
Strictly speaking, the process cannot be considered as truly tropose-
lective since the process involves complete racemization of the
reaction center.
¡
[13] G values expressed as the number of molecules produced per 100 eV
[22] M. Aschi, M. Attina, F. Cacace, G. D'Arcangelo, J. Am. Chem. Soc.
‡
of energy absorbed by the gaseous mixture: G(CnH5 ) ˆ 1.9 (n ˆ 1),
1998, 120, 3982.
0.9 (n ˆ 2) (P. Ausloos, S. G. Lias, R. Gorden, Jr., J. Chem. Phys. 1963,
39, 3341).
[23] In ref. [7], the observation of an identical positional selectivity for
both the alkyl cation/arene and the arenium ion/alkene reactions is
taken as an evidence in favor of a stepwise mechanism via consecutive
a-complex > b-complex conversions and, therefore, against any
alternative concerted mechanism. This logical link is not any longer
acceptable if one considers the intervention of common low-energy,
tightly-bound h1-type complexes in both reaction coordinates
(Figure 1).
[14] The collision constant kcoll between the arenium ions of Scheme 1 and
(C2H5)3N is calculated according to: T. Su, W. J. Chesnavitch, J. Chem.
Phys. 1982, 76, 5183.
[15] a) D. Berthomieu, H. E. Audier, C. Monteiro, J. P. Denhez, Rap.
Commun. Mass Spectrom. 1991, 5, 415; b) H. E. Audier, C. Monteiro,
P. Morgues, D. Berthomieu, Org. Mass Spectrom. 1990, 25, 245.
[16] Protonation of p-xylene is practically unselective with respect to the
six ring positions (J. L. Devlin, III, J. F. Wolf, R. W. Taft, W. J. Hehre, J.
Am. Chem. Soc. 1976, 98, 1990). The irradiated systems invariably
contain H2O as ubiquitous impurity either initially introduced in the
Received: July 24, 2002
Revised: December 18, 2002 [F4281]
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Chem. Eur. J. 2003, 9, 2072 2078