Fries rearrangement of aryl formates promoted by BCL3. Mechanistic evidence from 11B NMR spectra and DFT calculations

Article abstract of DOI:10.1515/znb-2004-0406

The Fries rearrangement of model aryl formate esters, promoted by boron trichloride, has been investigated by means of NMR spectroscopy (both experimental and computational) and by DFT calculations. Firstly, the ¹¹B NMR chemical shifts of a series of model boron compounds have been predicted by GIAO-B3LYP/6-31G(d,p) calculations, in order to make predictions of the chemical shifts of transient reaction intermediates observable by ¹¹B NMR. Such ¹¹B spectra for the reaction of two esters (phenyl and 3-methyoxyphenyl formates) have been obtained, and are found to follow different patterns which can be rationalized on the basis of computed chemical shifts. Secondly, DFT calculations (B3LYP/6-31G(d,p) level) have been employed to investigate several mechanistic pathways of the rearrangement of phenyl formate. It is found that the pathways leading to the lowest activation energies are those in which formyl chloride is generated from a complex between phenyl formate and BCl₃, which then acts as the formylating agent.

Full text of DOI:10.1515/znb-2004-0406

Fries Rearrangement of Aryl Formates Promoted by BCl3.
Mechanistic Evidence from 11B NMR Spectra and DFT Calculations*
Alessandro Bagnoa, Willi Kantlehnerb, Ralf Kreßb, and Giacomo Saiellic
a Department of Chemistry, University of Padova, via Marzolo 1, I-35131 Padova (Italy)
b Institut fu¨r Organische Chemie der Universita¨t Stuttgart, Pfaffenwaldring 55,
D-70569 Stuttgart (Germany)
c Institute of Membrane Technology-CNR, Padova Section, via Marzolo 1, I-35131 Padova (Italy)
Reprint requests to Prof. Alessandro Bagno. Fax: +39 0498275239.
E-mail: alessandro.bagno@unipd.it
or Prof. Dr. Willi Kantlehner. Fax: +49 07361 576250. E-mail: willi.kantlehner@fh-aalen.de
Z. Naturforsch. 59b, 386 – 397 (2004); received January 7, 2004
The Fries rearrangement of model aryl formate esters, promoted by boron trichloride, has been
investigated by means of NMR spectroscopy (both experimental and computational) and by DFT
calculations. Firstly, the 11B NMR chemical shifts of a series of model boron compounds have been
predicted by GIAO-B3LYP/6-31G(d,p) calculations, in order to make predictions of the chemical
shifts of transient reaction intermediates observable by 11B NMR. Such 11B spectra for the reaction
of two esters (phenyl and 3-methyoxyphenyl formates) have been obtained, and are found to follow
different patterns which can be rationalized on the basis of computed chemical shifts. Secondly,
DFT calculations (B3LYP/6-31G(d,p) level) have been employed to investigate several mechanistic
pathways of the rearrangement of phenyl formate. It is found that the pathways leading to the lowest
activation energies are those in which formyl chloride is generated from a complex between phenyl
formate and BCl3, which then acts as the formylating agent.
Key words: Fries Rearrangement, Reaction Mechanisms, Electrophilic Reactions,
DFT Calculations, 11B NMR
Introduction
The Fries rearrangement transforms an aryl ester
into an ortho- or para-hydroxycarbonyl compound
with Lewis-acid catalysis, thus providing a convenient
route to obtain aromatic ketones [1]. Standard catalysts
Scheme 1. Fries rearrangement of aryl formates.
are aluminum chloride or boron trifluoride. The high nium trifluoromethanesulfonate [6], scandium triflu-
preparative value of this reaction render this reaction oromethanesulfonate [7], zirconium tetrachloride [8]
an attractive path, for which there is continuing inter- and titanium tetrachloride [9] have all been used to in-
est, as attested by several reviews, the most recent one duce the rearrangement. Novel reaction methodologies
dated 1992 [2].
have also been applied; Fries rearrangements have also
been performed under microwave irradiation [10] or in
ionic liquids [11].
Extending the Fries rearrangement to aryl formates
is particularly attractive, since it would enable one
to introduce a valuable aldehyde functionality. Al-
though the first attempts at doing so (using BF3, HF,
polyphosphoric acid or AlCl3) failed [12– 14], it was
As can be seen from the number of papers which
appeared during the last years, the Fries rearrange-
ment is still a fascinating object of investigation
for organic chemists. Thus, a wide variety of cata-
lysts such as polyphosphoric acid [3], methanesul-
fonic acid/POCl3 [4], montmorillonite clays [5], haf-
* Presented in part at the 6th Conference on Iminium Salts recently demonstrated that alkoxyaryl formates can be
(ImSaT-6), Stimpfach-Rechenberg (Germany), September
16 – 18, 2003.
rearranged according to Fries giving alkoxy-hydroxy-
substituted benzaldehydes, if Lewis acids (such as
c
0932–0776 / 04 / 0400–0386 $ 06.00 ꢀ 2004 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
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A. Bagno et al. · Fries Rearrangement of Aryl Formates Promoted by BCl3
387
boron trichloride or boron tribromide) or superacids (400.13 MHz for 1H, 128.38 MHz for 11B) at the specified
temperatures. The measurements were run without lock in
5-mm tubes, which was allowed for by the magnet stability
and very short measuring times. For 11B NMR, the follow-
ing main parameters were adopted: π/2 pulse 26.5 µs, spec-
tral window 12 kHz, relaxation delay 1 ms. The combination
of high sensitivity of 11B and its relatively fast relaxation al-
lowed to obtain spectra with an excellent S/N ratio in a matter
of 2 – 3 minutes.
(such as trifluoromethanesulfonic acid) are used as cat-
alysts (Scheme 1) [15].
Despite several studies, no satisfactory and com-
prehensive mechanistic picture for this reaction has
emerged, also owing to the variety of combinations of
substrate and catalyst that have been adopted [1]. There
is consensus that the reaction proceeds through a 1:1
(or possibly 1:2 [16]) adduct with the Lewis acid cat-
alyst, and that the carbonyl functionality is introduced
through a Friedel-Crafts acylation, presumably via an
acylium ion intermediate [1]. With CF3SO3H as cata-
lyst, the reaction is known to be reversible [17]. How-
ever, other major mechanistic features are not well es-
tablished. Thus, the rearrangement has been claimed to
be: (a) intermolecular for both the ortho and para iso-
mers [18]; (b) intramolecular (at least for the ortho iso-
mer) [19], or (c) both (albeit in a polymeric substrate
system) [20].
DFT calculations of structures, energies and nuclear
shieldings were carried out with Gaussian 98 [21] at the
specified levels of theory, except relativistic calculations on
some boron calibration compounds (see Results) which were
performed with the ADF [22] package.
Results and Discussion
Esters [R–C(O)–OR’] possess two sites capable of
acting as a Lewis base, i.e. the oxygen of the alcohol
residue (–OR’) and the acyl oxygen, R–C(O). Thus, in
principle BCl3 may bind to the formate ester in each
In any event, there is little knowledge concerning
the detailed steps of each mechanistic proposal. Thus, of the following ways (O-aryl or O-acyl complexation,
most studies broadly agree on a picture where an un- Scheme 2):
specified complex between substrate and Lewis acid
undergoes a dissociative (rather than concerted) path-
way, whereby an acylium cation (or acyl chloride) is
expelled and subsequently acts as acylating agent [16–
20]. On the other hand, a π complex between the
acylium ion and the aromatic substrate has been pro-
posed to account for the observed intramolecular pro-
cess [19].
These circumstances have prompted us to pursue
this topic from two novel viewpoints. Thus, we built
on previous experimental results pertaining to the Fries
rearrangement promoted by boron trichloride, as fol-
lows [15]. On one hand, we obtained 11B NMR spectra
during the reaction course and attempted to understand
Scheme 2. Possible complexation modes of phenyl formate
the 11B spectra of reaction intermediates through the
with boron trichloride.
comparison with chemical shifts calculated by density
functional theory (DFT). On the other hand, we inves-
A straightforward way to represent the initial stage
tigated a variety of viable reaction mechanisms, again
(addition of the Lewis acid) is O-aryl complexation (a).
by DFT calculations, in order to clarify some mecha-
However, calculations of the protonation site of formic
nistic issues.
acid and methyl formate have shown that O-aryl pro-
tonation is not only much less favorable energetically
Experimental and Computational Section
than O-acyl protonation, but also leads essentially to
C–O fission and to a loose complex between water (or
alcohol) and the acylium cation [23]. Since BCl3 com-
plexation is a qualitatively similar phenomenon, the
energetics of this reaction should be investigated, and
Aryl formates and BCl3 (heptane solution) were commer-
cial. The samples were prepared by rapidly mixing the aryl
formate and the BCl3 solution so as to attain a 1:1 molar
mixture in heptane. 1H and 11B NMR spectra were obtained
on a Bruker Avance DRX 400 instrument operating at 9.4 T mechanisms involving both O-aryl and O-acyl com-
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388
A. Bagno et al. · Fries Rearrangement of Aryl Formates Promoted by BCl3
Scheme 3. Proposed mechanistic pathways for the O-aryl complex.
plexation should be considered. A mechanistic spec- Path (b): O-Acyl complex
trum may then be proposed as follows. The O-aryl (a)
Path (b1) involves an initial loss of Cl− from the
and O-acyl (b) complexes may react as sketched in
Schemes 3 and 4, respectively, which will be examined
in turn.
adduct, its readdition with rearrangement with the for-
mation of the intermediate C, proceeding to B as
seen before through A (see Scheme 4). Once again,
the rearrangement step requires a 4-membered cyclic
TS. Alternatively, Cl− may recombine with the sub-
strate to give rise to the neutral intermediate D (a
chloroalkyl-dichloroborate) before undergoing the re-
arrangement (b2). A further mechanism, which avoids
a strained TS, is represented in (b3): intermediate D
adds to a further substrate molecule via its aryl oxy-
gen, and a phenyl formate molecule is exchanged via a
6-membered cyclic TS, yielding again A. Finally, one
can consider path (b4), similar to (a3), where a direct
FC acylation takes place.
Path (a): O-Aryl complex
Path (a1) postulates an initial loss of Cl− from
the adduct (see Scheme 3). Subsequent readdition
to the carbonyl group may trigger a rearrangement
to yield the intermediate A, which eventually under-
goes an intramolecular Friedel-Crafts acylation lead-
ing to the aryl-dichloroborate B and is eventually hy-
drolyzed to the final product. (Indeed, for the pur-
poses of this work B can be viewed as the product
since its hydrolysis will not be rate-determining). The
transition state (TS) leading to A is a four-membered
A few general and speculative remarks can be given
ring, and as such it is expected to be relatively unfa- at this point. (1) Both types of BCl3 complexation
vorable. Path (a2) envisions the formation of a “free” can, in principle, account for the products, cfr. (a1)
formylium cation through C–O cleavage, whereby the and (b1-4). (2) In many cases, a 4-membered cyclic
corresponding para isomer B may also form. How- TS, as well as substantial conformational changes,
ever, the high energy of HCO+ calls for some cau- must be involved. Even though such processes may be
tion in invoking its intermediacy. It might also be ar- favorable entropically, the viability of these strained
gued that the actual electrophilic species is formyl species remains questionable and should be assessed.
chloride, HCOCl. Finally, there might be a direct in- (3) In paths (a1), (a3), (b1-4) the electrophilic cen-
tramolecular Friedel-Crafts (FC) acylation where the ter is not separated from the aromatic ring (regardless
electrophile is the incipient formylium ion (a3). Again, of whether Cl− exchange is intermolecular); hence,
this path involves a strained cyclic TS; however, O-aryl only ortho products are expected. (4) Path (b3) is a
complexation might involve lengthening of the C–O transformylation from another ester molecule. It re-
bond (see above), which might lead to increased re- quires initial complexation via the aryl oxygen, fea-
activity.
tures a 6-membered cyclic TS and hence may be much
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A. Bagno et al. · Fries Rearrangement of Aryl Formates Promoted by BCl3
389
Scheme 4. Proposed mechanistic pathways for the O-acyl complex.
less strained. (5) Pa−th (a2) leads to a loose complex cal shift. This study involved the comparison between
between Ph–OBCl3 and a formylium cation. Chlo- two similar aryl formates showing different reactivity,
ride abstraction might lead to HCOCl, which may be i. e. phenyl and 3-methoxyphenyl formate, the former
the actual formylating agent. In this case, para acy- being unreactive under the specified conditions (see In-
lation may take place. However, the existence of the troduction).
free formylium cation is very uncertain, and its life-
time is probably too short to act as formylating reagent.
Hence, the free formylium ion should not, if possi-
ble, be invoked as an intermediate (6). It should be re-
called that the boron species envisaged above are only
a simplification. In practice, one can expect multiple
additions (with corresponding loss of a further chlorine
atom).
Furthermore, we have studied the relative stabil-
ity of O-aryl and O-acyl complexes of a model sub-
strate (phenyl formate) with BCl3, the intermediates
sketched in Schemes 3 – 4, as well as the potential en-
ergy surface (PES) for the major expected pathways,
with the aim to characterize major intermediates and
transition states.
Guided by these considerations, we have undertaken
a combined experimental and theoretical investigation,
along the following lines.
Structure and energetics of phenyl formate-BCl3
adducts
We have investigated the 11B NMR chemical shifts
This process has been investigated theoretically by
of all conceivable intermediates, in connection with the DFT methods (B3LYP/6-31G(d,p), with geometry op-
experimental NMR study via 11B NMR at low tem- timization at the same level). Firstly, two conformers
perature of the addition of BCl3 to aryl formates, the of phenyl formate have been located: (a) (planar) and
aim being to distinguish them according to the effect (b) (non-planar), a being more stable by 1.6 kcal/mol
of the different coordination type on the 11B chemi- (Scheme 5).
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390
A. Bagno et al. · Fries Rearrangement of Aryl Formates Promoted by BCl3
it might constitute a bona fide activated substrate,
whereas the O-acyl one might be more stable but ki-
netically inactive.
Calculation of 11B NMR spectra
The naturally occurring boron isotopes are 10B (I =
3, 20%) and 11B (I = 3/2, 80%) [26]. The latter is the
most frequently used in NMR investigations, owing to
its higher receptivity and natural abundance. Since this
nuclide possesses an electric quadrupole moment Q, its
relaxation is relatively fast and the achievable resolu-
tion is only fair. However, since Q is small, line widths
are acceptable for many small molecules, thus leading
to a series of peaks for each boron species contained in
a given sample. Spin-spin coupling may or may not
be detectable, depending on various factors [26]; in
Scheme 5. Structures of phenyl formate and its complexes
with BCl3 (B3LYP/6-31G(d,p) geometry). In (a) and (b)
two stable conformers of phenyl formate are represented,
whereas (c) and (d) depict the structure of the O-acyl and
O-aryl adducts, respectively.
any event, the kind of species of interest for this work
would not exhibit any relevant coupling since boron is
directly bonded to O or Cl.
Even though a large number of boron species have
been characterized by 11B NMR [26], identification
of unstable species by this technique requires an in-
dependent evaluation of such NMR spectral parame-
ters, notably the chemical shift. Lately, much progress
has been made in this field, and density-functional
methods have proved effective at this prediction
[27, 28].
The structure of the O-aryl adduct (Scheme 5d) is
that of a loose complex strongly reminiscent of the
isolated partners; thus, the B–O distance is very long
˚
(3.21 A), and the BCl3 moiety retains its planar ar-
rangement. There is, however, a detectable elongation
˚
(∆r = 0.01 A) of the C(O)–O bond. Overall, it is con-
Hence, we ran a series of calculations aimed at cali-
brating the performance of a DFT method for a variety
of boron-containing species. These calculations have
mostly been carried out with the GIAO-DFT method
at the B3LYP/6-31G(d,p) level of theory, for a series
of model boron compounds and of proposed reaction
intermediates. This relatively small basis set has been
chosen in view of the size of the largest molecules
to be investigated (triaryl borates). In this framework,
the isotropic part of the nuclear shielding tensor σ is
made of the two diamagnetic and paramagnetic con-
tributions (σ = σd + σp), and the calculated chemical
shift is given by δ = σref −σ, σref being the shielding
of the reference compound (BF3·OEt2).
sistent with the weak energetics of interaction (see be-
low). On the contrary, the O-acyl adduct (Scheme 5c)
˚
features a fairly short B–O bond (1.62 A), a substantial
˚
lengthening of the C=O bond (∆r = 0.04 A), and the
BCl3 moiety takes the expected “tetrahedral” arrange-
ment.
Absolute BCl3 affinities (∆E), after correction for
the basis-set superposition error (BSSE),[24] show that
O-aryl complexation is essentially thermoneutral (ac-
tually slightly repulsive), whereas O-acyl complexa-
tion takes place with a stabilization of 28 kcal/mol.
(The BSSE correction is essential because absolute en-
ergies differ very little otherwise). This is in qualita-
tive agreement with the calculated results for the pro-
tonation of formic acid and methyl formate (where
Most species relevant to this study contain three
relative stabilities differ by ca. 20 kcal/mol) [23], chlorine atoms. The direct bonding of heavy atoms
or protonation and AlCl3 addition to amides (15– to a light one is known to entail marked, and some-
30 kcal/mol) [25]. However, since the O-aryl approach times dramatic, effects on the chemical shift of
is not strongly destabilizing (nor it leads to bond fis- the light-atom nucleus (e.g. the 13C chemical shift
sion like in the case of proton transfer) the O-aryl of tetraiodomethane at δ = −290 ppm), which are
complex may remain a viable intermediate – indeed, due to relativistic spin-orbit coupling effects [29].
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A. Bagno et al. · Fries Rearrangement of Aryl Formates Promoted by BCl3
391
Table 1. Experimental and calculated 11B chemical shifts.a
Species
Known species:b
δfound
δcalcd.
BF3OEt2
0
0
−
BH4−
−40
−2.2
6.6
47
−47
−2.4
18
BF4
BCl4
−
BCl3
50
PhBCl2
Ph2BCl
B(CH3)3
55
61
86
56
72
77
Unknown species:c
MeOBCl2
32
32
20
11
32
20
9.8
40
19
50
11
19
51
d
o-C6H4(CHO)OBCl2
Scheme 6. Proposed key reaction intermediates.
[o-C6H4(CHO)O]2BCld
[o-C6H4(CHO)O]3dBd
PhOCH(Cl)OBCl2
fore, at least a first assessment of relativistic effects
on 11B shifts is in order. This check was performed
by running calculations at the spin-orbit relativistic
ZORA level with a triple-zeta, polarized Slater ba-
[PhOCH(Cl)O]2BCld
[PhOCH(Cl)O]3Bd
+
PhOCHOBCl2
HCOOPh-BCl3, via acyl Oe
HCOOPh-BCl3, via aryl Oe
B(OPh)3
sis set [22]. In this framework, σ = σd + σp + σSO
.
)
The spin-orbit contribution to the 11B shielding (σSO
B(OPh)2Cl
B(OPh)Cl2
turns out to be negligible for non-chlorinated species,
small (5 and 8 ppm for BCl3 and BCl4−, respectively)
for polychlorinated species, but substantial for bromi-
nated species (up to 52 ppm for BBr4−). Therefore,
keeping in mind the rather low accuracy of chemical
shifts, it is not necessary to include this contribution
(but it would be if one wished to consider BBr3 as
Lewis acid, since the relativistic effect would not be
compensated for by the reference), and all further cal-
culations have been carried out at the non-relativistic
B3LYP/6-31G(d,p) level. The calibration results (ex-
cluding Br compounds) are plotted in Fig. 1, showing
that a good accuracy can be attained at this level of
theory, considering the relatively low resolution than
can be experimentally achieved. Note, however, that
the correlation would become much worse for the rea-
sons just discussed if bromine-containing species were
included.
a
b
Referred to BF3OEt2 as standard. δcalcd. = σ − σref
;
data from
ref. [26]; c calibration species for which an experimental value is not
available; d see Scheme 6; e see Scheme 5c,d.
Several species of the type B(OAr)mCln (m+n = 3)
have been calculated (Table 1). The calculated 11B
chemical shift of the O-aryl complex of phenyl formate
is 50 ppm, i.e. very close to that of BCl3 itself, as ex-
pected for the very weak interaction already presented
(see above). The calculated shift of the O-acyl complex
Fig. 1. Correlation between experimental and calculated 11
B
chemical shifts (data from Table 1). Bromine-containing
compounds are excluded since they show major deviations
from the correlation (see text). The linear regression has
slope 1.01, intercept 0.95 ppm, r = 0.97.
Even though chlorine is a far lighter atom than io- is, instead, rather different (19 ppm), i.e. well above
dine, similar (if much smaller) effects have been experimental resolution. Otherwise, all B(OAr)mCln
found for 13C in species like dichlorophenols and o- species with the same m and n have very similar shifts,
bromochlorobenzene [30]. This effect calls for some regardless of the structure of the Ar group: δ32(n = 2);
caution when evaluating these calculated shifts. There- δ20(n = 1); δ10(n = 0) (Scheme 6).
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392
A. Bagno et al. · Fries Rearrangement of Aryl Formates Promoted by BCl3
Fig. 3. 11B NMR Spectra of the 3-methoxyphenyl formate-
BCl3 mixture. Lower trace: After mixing at −10 ◦C; middle
trace: 0 ◦C; upper trace: after thawing at 20 ◦C.
Fig. 2. 11B NMR Spectra of the phenyl formate-BCl3 mix-
ture. Lower trace: After mixing at −10 ◦C; middle trace: after
24 h at −10 ◦C; upper trace: after thawing at 20 ◦C.
nal is compatible with both PhOCH(Cl)OBCl2 (D) and
the rearranged intermediate B, o-C6H4(CHO)OBCl2.
Since, however, the reaction does not actually proceed
with phenyl formate, only the first option is consis-
tent with the results. Hence, presumably the final prod-
uct from this unreactive ester is PhOCH(Cl)OBCl2
(D). The signal observed at δ = 27 ppm at low tem-
perature may be an (ArO)2BCl species (estimated at
δ = 20 ppm, Table 1).
11B NMR spectra of phenyl and 3-methoxyphenyl for-
mates with BCl3/heptane
The reaction of phenyl and 3-methoxyphenyl for-
mate with BCl3 in heptane has been run at low
(−10 ◦C) to room temperature, monitoring its progress
by means of 11B NMR spectroscopy (Figures 2 – 3).
11B spectra were recorded immediately after mixing at
−10 ◦C, and again after letting the sample thaw to 0 ◦C.
A final spectrum was recorded after the sample was al-
lowed to slowly thaw to 20 ◦C.
No 11B spectrum, even immediately after mixing,
shows peaks that can be assigned to “free” BCl3 (δ =
47 − 50 ppm), which indicates that the Lewis acid is
strongly interacting with the substrate (regardless of
whether this interaction causes further reaction or not).
Instead, both substrates display a major 11B signal at
δ = 14−15 ppm, which (by comparison with the cal-
culations) corresponds to the value for the O-acyl com-
plex with BCl3.
(b) 3-Methoxyphenyl formate. The spectrum (Fig. 3)
initially shows again a major peak at δ = 16 ppm
(again, presumably, the O-acyl complex) and a fairly
strong peak at δ = 8.3 ppm. When the sample is al-
◦
lowed to thaw to 0 C, the peak at δ = 8.3 ppm
becomes the main signal, but is accompanied by
rather weak ones at δ = 15 (O-acyl complex), 18
(not assigned) and◦ 32 ppm (B or D). When fur-
ther thawed to 20 C, the the peak at δ = 8.3 ppm
remains the strongest signal, with minor ones at
δ = 26 and 32 ppm. Upon standing at room tem-
perature, the latter two signals disappear and only
the one at δ = 8.3 ppm remains. Its chemical
shift lies in a range typical of trialkyl- or triaryl-
oxyborates like [3-OMe–C6H4–CH(Cl)O]3B or [3-
OMe–C6H3(CHO)O]3B (Scheme 6). Since the Fries
rearrangement actually proceeds, the peak at δ =
8.3 ppm may be assigned to the rearranged interme-
diate.
(a) Phenyl formate. Right after mixing, essentially
only the peak at δ = 14 ppm is present (Fig. 2). If the
sample is left standing at −10 ◦C for 24 h, the peak at
δ = 14 ppm disappears, and is replaced by two addi-
tional peaks at δ = 27 and δ = 32 ppm. Upon thaw-
◦
ing to 20 C, the peak at δ = 32 ppm becomes the
most prominent one, although some minor peaks be-
Thus, these data indicate that the two substrates re-
tween δ = 17 − 27 ppm are also detectable. This sig- act rather differently with BCl3; only in the latter case
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A. Bagno et al. · Fries Rearrangement of Aryl Formates Promoted by BCl3
393
Fig. 4. Potential energy surface for the in-
tramolecular Friedel-Crafts acylation from
the O-aryl complex, path (a3). The step
marked as “NO RDS” is assumed to be not
rate-determining.
Fig. 5. Potential energy surface
for the intramolecular Friedel-
Crafts acylation from the O-acyl
complex, path (b4). The step
marked as “NO RDS” is assumed
to be not rate-determining.
BCl3 adds three molecules of aryl formate, and the for- parison among different mechanistic path-ways.
mation of these intermediates marks the progress of
the reaction. Unfortunately, however, 11B NMR can-
not discriminate between unrearranged and rearranged
intermediate.
Direct intramolecular Friedel-Crafts acylation:
paths (a3) and (b4). We will start our discussion
with the two alternative mechanisms based on an in-
tramolecular Friedel-Crafts acylation (paths (a3) and
(b4) in Schemes 3 and 4). The conversion from the
Wheland intermediate to o-hydroxybenzaldehyde was
assumed to be non-rate-determining, and no TS was
DFT study of the mechanism of Fries rearrangement
All calculations were carried out at the B3LYP/6-
31G(d,p) level. The geometry of all reactants, transi- searched for this step in both cases.
tion states, intermediates and products were optimized
at that level, and the nature of the critical points was
verified by vibrational analysis, confirming that the
imaginary vibration led in fact to the desired transfor-
mation. Transition-state geometries were optimized by
means of the Quadratic Synchronous Transit method,
but no IRC analysis was performed [21].
All calculations involved phenyl formate as model is partially formed in the TS (2.39 A). The imaginary
substrate. It should be remarked at the outset that, since vibrational mode in the TS represents the shift of the
this compound is not reactive, all activation energies HCO+ fomylium ion from the aryl O to the C of the
should be considered as an upper bound to those of re- benzene ring. The structures and energies of the three
active esters, and the results will only serve for a com- stationary states are collected in Fig. 4.
Complexation of the ester at the aryl oxygen by
BCl3, path (a3), yields the weakly bound complex of
Scheme 5d. In the TS, the complexation of the aryl
oxygen becomes much stronger (the B–O bond length
˚
˚
is 1.51 A, compared with 3.21 A in the reactant com-
plex), whereas the C–O(aryl) bond is increased from
˚
1.36 to 2.14 A. At the same time the C–C(aryl) bond
˚
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394
A. Bagno et al. · Fries Rearrangement of Aryl Formates Promoted by BCl3
Fig. 6. Potential energy surface for path
(b2).
Path (b4) is similar to Path (a3): an intramolecular
FC acylation takes place, this time starting from the
O-acyl complex (Scheme 5c). As far as the energet-
ics is concerned, paths (b4) and (a3) are very simi-
lar. However, there is a large difference in the struc-
ture of the four-membered ring: for path (a3) (com-
plexation at the aryl O), the C–O and C–C bonds are
˚
much longer (2.14 and 2.39 A), while for path (b4)
(complexation at the acyl O), these bonds are shorter
˚
(1.50 and 1.70 A, respectively). The structures and en-
ergies of the three stationary states are collected in
Fig. 5.
Friedel-Crafts acylation by HCOCl generated in
situ: paths (b1) and (b2). Starting from the more stable
O-acyl complex it is possible to have loss of Cl− and its
subsequent readdition to the carboxyl carbon yielding
PhOCHClOBCl2 (D). The intramolecular rearrange-
ment with loss of HCOCl is repesented in Fig. 6,
path (b2). The breaking C–O bond at the TS is quite
˚
elongated (1.87 A), i.e. resembling a weakly bound
complex between PhOBCl2 and HCOCl (a product-
like TS).
Fig. 7. Potential energy surface for path (b1). (a) B···Cl as-
sisted; (b) B···O assisted.
Path (b2) can be viewed as the initial stage for the
subsequent acylation of PhOBCl2 by HCOCl, which
is represented by path (b1). Thus, starting from the
complex between PhOBCl2 and HCOCl, the reaction
may proceed further through a normal FC addition to
the aromatic ring. In principle, this may occur both
at the ortho and para positions, activated by OBCl2
group. The ortho addition may be favoured by a sta-
bilizing interaction of the electrophilic B atom with a
Cl or O atom of formyl chloride (B···Cl or B···O as-
sisted; see below). Herein, we will only discuss the or-
tho addition.
This electrophilic addition to the ring may itself take
place in two ways, i. e. through assistance by a chlorine
atom (B···Cl assisted), or by an oxygen atom (B···O
assisted). Both have been investigated, and the results
are presented in Figures 7a – b. In the first case, the re-
sulting Wheland intermediate would directly lead to B,
whereas in the second one it is the formal adduct of
formyl chloride. These TS’s also differ in the extent
of advancement of electrophilic addition. In the case
of B···Cl assistance (Scheme 7a, higher-energy TS),
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A. Bagno et al. · Fries Rearrangement of Aryl Formates Promoted by BCl3
395
Fig. 8. Potential energy surface for path (b3).
˚
the C–C bond being formed has a length of 2.15 A
with a rather small distortion of the aromatic ring
from planarity, whereas in the case of B···O assis-
tance (Scheme 7b, lower-energyTS), the same distance
˚
amounts to 2.10 A and the ring distortion is stronger.
Therefore, the latter TS is more product-like.
Transformylation: path (b3). This pathway involves
intermediate D, which adds a further ester molecule at
the aryl oxygen, exchanges a formyl group and falls
back to a complex between PhOBCl2 and HCOCl, ex-
pelling an ester molecule and presumably entering path
(b1); see Fig. 8.
The calculated transition-state structures are col-
lected in Fig. 9.
Of all the pathways examined, paths (a3) and (b4)
are found to exhibit the highest activation barriers
(> 40 kcal/mol), consistently with the strained nature
of their transition states. Hence, even though from a
purely energetical viewpoint they are probably much
less favored than the others, such mechanisms might
be favored entropically.
On the other hand, pathways (b2) and (b3), with
lower activation barriers (23 and 31 kcal/mol, respec-
tively), are simply different preparation stages for the
subsequent step (b1), in that both pathways repre-
sent different modes of generation of formyl chlo-
ride as the active electrophile, which eventually acy-
lates PhOBCl2. This step may itself occur in two
ways, i.e. with assistance from Cl or O (Fig. 7). Since
the latter features the smaller activation energy (23
vs. 35 kcal/mol) we will assume B···O assistance
(Fig. 7b) in the remaining discussion.
Fig. 9. Calculated structures of the transition states for all
mechanisms investigated. Some relevant interatomic dis-
tances are given in A.
˚
estingly, the activation barrier for its decomposition to
PhOBCl2 + HCOCl is much smaller than for paths (a3)
and (b4) despite a superficially similar nature (in both
cases a four-membered ring is involved, but in this case
all bonds are longer).
The final pathway (b3) (transformylation) exhibits
a somewhat larger activation energy at 31 kcal/mol;
moreover, the complex mode of approach involved
may indicate that entropic factors will work against it
despite its relatively unstrained geometry. In any event,
occurrence of this mechanism might be detected as a
different kinetic profile (presumably second-order in
ester substrate).
In the first case, path (b2) envisions the formation of
We also note that, of all the TS’s determined, only
intermediate D (Scheme 4) through Cl− loss and read- the one for path (b1), B···Cl-assisted, somewhat re-
dition from the O-acyl complex; we note that D is only sembles a π complex between the formylium cation
marginally higher in energy than its precursor. Inter- and the aromatic ring, which was suggested as the sta-
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396
A. Bagno et al. · Fries Rearrangement of Aryl Formates Promoted by BCl3
blizing factor leading to intramolecular rearrangement deliberately added to the reaction mixture) to induce
[19]. the bond breakage. The corresponding mechanism in
Finally, we recall the work by Hart and coworkers our system will be investigated in a further work.
[31], who employed 27Al and 17O NMR to probe the
In summary, the current data favor a complex mech-
−
role of AlBr4 in the Fries rearrangement of phenyl anism where the active formylating agent is formyl
benzoate promoted by AlBr3. These investigations led chloride, generated in situ from decomposition of suit-
to a proposed mechanism where the O-acyl com- able reactive intermediates, paths (b2) and (b3). Of
plex between PhC(O)OPh and AlBr3 undergoes a C– course, these results open up the regioselectivity is-
O(aryl) bond fission mediated by AlBr4−, leading to sue, since the intermolecular acylation step might con-
a “tight ion pair” [PhCO+ ·PhOAlBr3−] which would ceivably lead to the para substituted product too (see
then undergo a pseudo-intramolecular(or “extramolec- above), which will also be the subject of further work.
ular”) acylation to yield the product with varying or- It should also be noted that the above pathways cannot
tho/para ratios. This proposal is essentially similar to be sorted out through the analysis of 11B NMR spec-
path (b2) presented herein, although the former re- tra, which however turn out to be a convenient progress
−
quires the explicit intervention of AlBr4 (sometimes monitor for the reaction.
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