Direct trifluoro-methoxylation of aromatics with perfluoro-methyl- hypofluorite

Article abstract of DOI:10.1016/j.jfluchem.2012.04.008

The reactivity of CF₃OF (FTM) has been widely studied especially in halogenated olefinic systems and its use in pharmaceutical synthesis as a mild radical and electrophilic fluorinating agent is well documented. On the other hand, the chemical behavior of the perfluoro-methyl-hypofluorite with aromatic substrates is much less studied. Up to now few and scattered data regarding its use as electrophilic fluorinating agent of variously substituted aromatic compounds are found in the literature. In this work the reactivity of CF₃OF with simple electron rich and electron poor aromatics (α,α,α-trifluoro-toluene, toluene, benzene, chloro-benzene, methoxybenzene) has been investigated. The possibility of selectively bind the trifluoro-methoxy group (via radical mechanism) or the fluorine atom (via electrophilic addition) by varying the reaction conditions has been explored. In particular we have observed that the trifluoro-methoxy free radical substitution can be the main synthetic pathway if the reaction is promoted by an independent and steady source of CF3O radical.

Full text of DOI:10.1016/j.jfluchem.2012.04.008

Journal of Fluorine Chemistry 140 (2012) 43–48
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Direct trifluoro-methoxylation of aromatics with perfluoro-methyl-hypofluorite
a
a,b,
a
a
Francesco Venturini , Walter Navarrini *, Antonino Famulari , Maurizio Sansotera ,
c
c
Patrizia Dardani , Vito Tortelli
a
Dipartimento di Chimica, Materiali e Ingegneria Chimica ‘‘Giulio Natta’’, Politecnico di Milano, Via Luigi Mancinelli, 7, 20133 Milan, Italy
Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali, Via G. Giusti, 9, 50121 Firenze, Italy
Solvay Specialty Polymers Italy, R&D Center, Viale Lombardia 20, 20021 Bollate (Milano), Italy
b
c
A R T I C L E I N F O
A B S T R A C T
Article history:
The reactivity of CF OF (FTM) has been widely studied especially in halogenated olefinic systems and its
3
Received 20 February 2012
Received in revised form 12 April 2012
Accepted 16 April 2012
use in pharmaceutical synthesis as a mild radical and electrophilic fluorinating agent is well documented.
On the other hand, the chemical behavior of the perfluoro-methyl-hypofluorite with aromatic substrates
is much less studied. Up to now few and scattered data regarding its use as electrophilic fluorinating
agent of variously substituted aromatic compounds are found in the literature. In this work the reactivity
Available online 24 April 2012
3
of CF OF with simple electron rich and electron poor aromatics (a,a,a-trifluoro-toluene, toluene,
Keywords:
benzene, chloro-benzene, methoxybenzene) has been investigated. The possibility of selectively bind the
trifluoro-methoxy group (via radical mechanism) or the fluorine atom (via electrophilic addition) by
varying the reaction conditions has been explored. In particular we have observed that the trifluoro-
methoxy free radical substitution can be the main synthetic pathway if the reaction is promoted by an
independent and steady source of CF3O radical.
Trifluoromethylhypofluorite
Aromatic trifluoro-ethers
Radical trifluoro-methoxylation
DFT calculations
ß 2012 Elsevier B.V. All rights reserved.
1
. Introduction
Aromatic trifluoro-ethers are key-intermediates [1] in the
Generally, the reaction pathway between hypofluorites and
unsaturated molecules is strongly dependent on the nature of the
alkene. Electron-poor alkenes exhibit a radical reactivity with the
formation of a trifluoromethoxylated ether [30–45] while elec-
tron-rich alkenes mostly undergo electrophilic fluorination as
shown in Scheme 1.
production of bioactive molecules [2] since fluorine atom imparts
desirable and valuable characteristics to drugs and pesticides [3,4].
The trifluoromethoxy group has increased utility as a substituent
in bioactive compounds, but remains perhaps the least well
understood fluorinated substituent currently in use [5–7]. Thus,
several synthetic routes to prepare trifluoromethoxy aromatic
derivatives have been developed over the last few years [8–22].
One of the most attractive option to synthesize this ether is the
direct reaction between an aromatic compound and trifluoro-
methyl-hypofluorite (FTM).
Trifluoro-methyl-hypofluorite is the simplest perfluoro-alkyl-
hypofluorite [23,24] and is one of the most widely used source of
trifluoro-methoxy group. It was first synthesized in 1948 by
passing methanol or carbon monoxide and fluorine over silver
difluoride at elevated temperatures [25–29]. Later, longer chain
hypofluorites were prepared by treating the appropriate carbonyl
compound with fluorine in the presence of dry cesium fluoride at
low temperatures [26,27].
The reactivity of CF
molecules has already been studied and reported in the specialized
literature [29,46]. It is recognized as mild electrophilic
3
OF (FTM) in the presence of aromatic
a
fluorinating agent of aromatic substrates as shown in Scheme 2.
However, this reaction is considered poorly convenient from the
industrial point of view because it is ‘‘atomistically’’ inefficient
since only one of the four fluorine atoms of the hypofluorite is used
to fluorinate the aromatic substrate.
The radical reactivity of FTM has been widely studied in the
presence of partially or fully halogenated olefinic systems and it is
known from these studies that the trifluoromethoxylating chain is
3
propagated by the CF O radical [46–49]. It was also found that by
changing the experimental conditions it was possible to force the
reaction path to follow preferentially one of the two possible
pathways (radical R or electrophilic E) [50–52]. From our study the
key intermediate that underlies the mechanism switch is the CF
3
O
radical because during the radical reaction between FTM and an
electron-poor alkene the CF
chain reaction.
By exploiting this mechanism we have investigated the
possibility to selectively bind, in one synthetic step, the
3
O radical is the carrier of the free radical
*
Corresponding author at: Dipartimento di Chimica, Materiali e Ingegneria
Chimica ‘‘Giulio Natta’’, Politecnico di Milano, Via Luigi Mancinelli, 7, 20133 Milan,
Italy. Tel.: +39 02 23993029.
E-mail address: walter.navarrini@polimi.it (W. Navarrini).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.04.008

4
4
F. Venturini et al. / Journal of Fluorine Chemistry 140 (2012) 43–48
Pure fluorine (99%) was bought from Solvay Fluor while pure
PMVE (trifluoromethyl-trifluorovinyl-ether, CF O–CF 55 CF ) was
3
2
supplied by Solvay Specialty Polymers Italy. A 25 bar gaseous
mixture of 3% PMVE in helium has been prepared and used for each
experiment. Carbon monoxide (99.8%) used for the carbonyl-
difluoride synthesis was purchased from Sapio.
Scheme 1. Radical (R) and electrophilic (E) addition pathway of perfluoro-methyl-
To avoid potentially dangerous decomposition of FTM the
pipelines of the continuous plant were cleaned and successively
passivated with diluted fluorine. In addition the FTM gas stream
was diluted with Helium in 1/5 (v/v) ratio. It is important to note
that only few and scattered data about the toxicity of the
trifluoromethoxylated aromatics are present in the literature.
Due to this fact it is mandatory to handle these products with care.
hypofluorite to alkenes.
trifluoro-methoxy group to a mono-substituted aromatic substrate
(
methoxybenzene, methylbenzene, benzene, chlorobenzene,
-trifluorotoluene) forming thus trifluoro-methoxy-aromatic
products (CF O-Ar).
a,a,a
3
It has been shown that the reaction could proceed following a
S.E.T. (single electron transfer) mechanism either producing the
fluorinated or the trifluoromethoxylated moieties [27,50,53,54].
Moreover the production of mono-fluorinated aromatics relies on
the fact that FTM is not highly polarized. Thus it has been proposed
that the reaction will be facilitated because the trifluoromethoxy
ion is an excellent leaving group that promptly decomposes to
carbonyl-difluoride and fluoride ion [27,50,53,54].
2.1. Hypofluorite additions
2.1.1. Electrophilic addition E
The procedure consists of bubbling a stream of hypofluorite
2
(5.5 NL/h: He = 80%, FTM = 18.5%, COF = 1.5%) into a solution of
the aromatic compounds maintained at the desired temperature
(À30 8C; À80 8C) in a semi-batch method [57].
In order to induce the production of CF
3
O radicals through
The solubility of the aromatic compounds was measured by
carrying out a cloud-point measurement in selected solvents. All
chemical initiation of FTM we have continuously added an
electron-poor alkene like PMVE (trifluoromethyl-trifluorovinyl-
the aromatics tested (
a,a,a-trifluoro-toluene, toluene, benzene,
3 2
ether, CF O–CF 55 CF ) to the reaction mixture (radical addition R).
chloro-benzene, methoxybenzene) are soluble at concentrations
The couple PMVE/TFM acts as in situ generator of trifluoromethoxy
radicals thus resulting in a one-step synthesis of aromatic-
trifluoro-ethers via radical addition as shown in Scheme 3. The
aromatic substrates have been chosen amongst electron-rich
between 4% and 5% in the chloro-fluoro-ether (CF
used as reaction solvent.
A cylinder containing 150 ml of a diluted (3%) solution of the
aromatic substrate in 1,2-dichlorotrifluoroethyl-trifluoromethyl-
3 2
OCFClCF Cl)
(
(
methoxybenzene, methylbenzene), benzene and electron poor
chlorobenzene, -trifluorotoluene) moieties.
3 2
ether (CF OCFClCF Cl) was prepared at room temperature. This
a
,a
,
a
solution was then poured in the 250 ml stainless steel stirred
reactor, cooled at À40 8C and then stripped with helium for 15 min
to eliminate the dissolved air since oxygen strongly interacts with
radical based mechanisms.
Subsequently the hypofluorite stream was bubbled in the
reactor kept at À40 8C under vigorous mechanical stirring. For one
mole of aromatic substrate only 0.05–0.88 mol of hypofluorite
were added, obtaining only a partial conversion of the aromatics.
2
. Material and methods
The main barrier that prevents a quick and in-depth study of
hypofluorite chemistry is related to safety. Hypofluorites are very
toxic and aggressive, thus any contact between these substances
and the operator must be avoided. The reactors and the
hypofluorite laboratory plant must be perfectly sealed and located
in an efficiently ventilated dedicated area [37,55]. Organic
hypofluorites should be regarded as potential explosives [56].
For safety reasons FTM was synthesized and used without any
2.1.2. Radical addition R
The procedure for the radical addition is identical to the
electrophilic methodology, but in addition it is characterized by
the simultaneous feeding of FTM and PMVE as radical ‘‘promoter’’.
For one mole of FTM less than 0.01 mol of PMVE were added during
the reaction.
For both the methodologies the gaseous streams were
constantly monitored by using an on-line GC-TCD (8 m PTFE
Kel-F oil packed column) and a Thermo Nicolet 380 FT-IR furnished
3
buffer storage. CF OF has been prepared in a PFR following a
modified literature procedure by catalytic fluorination of carbonyl-
difluoride on a fixed bed of porous metal fluorides [57–59]. This
approach makes use of an understoichiometric amount of fluorine
that helps avoiding the presence of fluorine traces in the FTM
stream and hence the formation of byproducts.
Scheme 2. S.E.T./electrophilic fluorination of aromatics with perfluoro-methyl-hypofluorite (electrophilic pathway E).
Scheme 3. S.E.T./radical reaction between aromatics and perfluoro-methyl-hypofluorite [64,65].

F. Venturini et al. / Journal of Fluorine Chemistry 140 (2012) 43–48
45
with a custom PTFE gas-phase cell with CaF
2
windows, volume
confirmed that they represent minimum-energy structures.
Atomic charges for carbon atoms were calculated as the best fit
to the molecular electrostatic potential (MEP) obtained at the
B3LYP/6-311G** level of the theory. Gavezzotti radii were used for
charges fitting. All calculations were performed with the GAMESS-
US suite of programs [64,65].
3
8
cm , 10 cm optical path.
At the end of the addition reaction the unreacted FTM, the
hydrogen fluoride and the dissolved carbonyl-difluoride were
partially removed by bubbling in the reactor 5 NL/h of helium for
about 3 h at À60 8C. After this stripping, the reactor cooling system
was stopped and the reactor was finally allowed to reach room
temperature. Stripping is a critical operation that serves to remove
the unreacted FTM from the liquid products. Any traces of
hypofluorite in the subsequent temperature ramp will likely
result in losing selectivity and may result in a fast temperature rise.
3. Results
During the radical addition, R, the presence of unreacted
3
hypofluorite in the off-gases has been observed. This fact is an
indication that the reaction media is saturated with a large amount
of FTM, as we have observed in a previous work [57]. By exploding
the reaction mechanism it is possible to notice that the reaction
with monosubstituted aromatics could proceed along with the
production of six isomers: three possible mono-fluorinated
isomers and three possible mono-(trifluoro-methoxylated) iso-
mers. The reaction with highly activated substrates could also
result, at high conversion, in the production of polyfluorinated
aromatics. Due to the presence of a large number of isomers
together with the solvent and the unreacted aromatic, the product
separation, purification and identification was troublesome. The
products were mainly qualitatively recognized using fragmenta-
tion data from GC–MS analyses. Isomer mixtures can be resolved
during GC analyses. GC peak areas have been used to estimate
product concentration and thus conversion by assuming a similar
response factor for similar substances. The raw data collected from
the GC analyses are summarized in Table 1.
The raw mixture was unloaded from the reactor into a 300 cm
cylinder and analyzed using a Thermo-Focus GC-TCD (Poraplot Q
column), an Agilent GC–MS system 6850-5975C (Poraplot U
column). A fractional distillation, at atmospheric pressure, using a
common glass distiller was then performed. Three fractions were
recovered: lightweights (Thead < 40 8C), solvent (Thead = 40–43 8C),
and residue (Tboiler > 50 8C). All the fractions were analyzed. 98% of
the total amount of aromatics was recovered in the residue
together with small amounts of solvent. The lightweights fraction
is mainly solvent with a purity higher than 98%.
+
MS trifluoromethoxy-anisole m/z (rel.int.): 50 [CF
2
] (24%), 69
+
+
+
+
[
(
(
CF
40%), 103 [C
4 2 3 3 6 4 3
45%), 177 [C H O F ] (78%), 192 [CH O–C H –OCF ] (401%). MS
3
] (100%), 75 [C
6
+
H
3
] (16%), 92 [C
6 4 7 2
H O] (20%), 101 [C H O]
+
+
7
H
3
O] (23%), 104.1 [C H O] (38%), 123 [C H O ]
7 4 7 7 2
+
+
7
+
+
2 3
trifluoromethoxy-toluene m/z (rel.int.) 50 [CF ] (23%), 69.2 [CF ]
+
+
+
(
(
[
100%), 90.2 [C
11%), 107.35 [C
7
H
6
]
(48%), 91.2 [C
7
H
7
]
(112%), 104.2 [C
7
H
4
O]
(70%), 174.35
(98%), 176.35 [CH –C
(314%). MS trifluoromethoxy-benzene m/z (rel.int.): 50
+
+
7
H
7 8 6 2
O] (16%), 156.25 [C H OF ]
+
+
C
8
H
5
OF
3
]
(14%), 175.25 [C
8
H
6
OF
3
]
3
6 4
H –
+
Traces of polyfluorinated aromatics have been found only at
high conversion in tests involving electron-rich aromatics like
methoxybenzene and toluene. In particular 2,5-difluoro-toluene
and benzyl-fluoride have been found in trials involving toluene
while in the tests with anisole the byproducts are mainly 2,4-
difluoroanisole, 3,4-difluoroanisole, fluoro-methoxy-benzene and
difluoro-methoxy-benzene.
OCF
3
]
+
+
+
[
CF
2
]
(16%), 69.05 [CF
O] (30%), 162.02 [C
omethoxy-benzene m/z (rel.int.) 50 [CF
3
]
(100%), 77.06 [C
6
H
5
]
(20%), 93.03
+
+
[
C
6
H
5
6
H
5
–OCF
3
]
(394%). MS chloro-trifluor-
+
+
2
] (17%), 69 [CF
3
] (100%),
+
+
+
7
3 [C
6
H] (34%), 74.1 [C
O] (19%), 127 [C
6
H
2
]
(17%), 75.1 [C
OCl] (50%), 196 [Cl–C
6
H
3
]
(42%), 92.1
+
+
+
[
(
(
(
[
(
C
6
H
4
6
H
4
6 4 3
H –OCF ]
502%). MS m-(trifluoromethoxy)-a,a,a
-trifluorotoluene m/z
+
+
+
rel.int.) 69.2 [CF HO]
3
]
(100%), 75.2 [C
+
6
H
4
]
(12%), 113.2 [C
8
+
28%), 114.2 [C H O] (34%), 133.2 [C H OF] (55%), 145.25
8 2 8 2
4. Discussion
+
+
+
C
7
H
4
F
3
]
(63%), 161.35 [C (12%), 211.4 [C
54%), 230.25 [CF –C –OCF ] (292%).
7
H
4
+
OF
3
]
8 4 5
H OF ]
3
6
H
4
3
The different products distribution and thus the observed
selectivity can be roughly explained by assuming a competition
between the radical induced reaction (Scheme 4) and the
electrophilic addition (Scheme 2). As it can be seen from Table
2.2. Computational details
Computational studies were carried out on the substrate
1, the electron density of the substrate plays an important role on
molecules under investigation. Minimum structures were
obtained by density functional theory (DFT) calculations: the
B3LYP hybrid functional [60–63] and the standard 6-311G** basis
set were adopted. A vibrational analysis was performed on
optimized geometries, where a lack of imaginary frequencies
the aromatic reactivity. The electron density on the aromatic ring
depends on resonance and inductive effects created by the ring
substituents. Values for the substrates used have been calculated
by performing DFT simulations. Table 2 reports atomic charges for
phenylic carbon atoms estimated as the best fit to the molecular
Table 1
Conversion, selectivity of the electrophilic (mono-fluorination), selectivity of the radical mono-(trifluoro-methoxylation) based on peak area for the electrophilic addition E
and radical addition R evaluated by GC analyses. Runs 4 and 5 were both performed using methylbenzene with the radicalic activator. It was not possible to clearly identify the
isomers in the analyses indicated with ‘‘n’’ thus the result has been omitted.
Run
Substrate
Addition
Aromatic conversion
Selectivity
Isomers distribution
Ar–OCF
3
Ar–F
1
2
3
4
5
6
7
8
9
Methoxybenzene
Methylbenzene
E
R
E
R
R
E
R
E
R
E
R
76%
77%
4%
11%
9%
58%
66%
40%
10%
45%
62%
46%
41%
23%
0%
Ortho and para isomers
Ortho and para isomers
50%
40%
44%
38%
54%
41%
66%
100%
100%
n
n
n
16%
70%
87%
75%
33%
44%
0.21%
0.06%
Benzene
Chlorobenzene
o/m/p: 7/1/8
o/m/p: 5/1/5.5
1
0
1
a
,a,
a-Trifluorotoluene
Meta isomer only
Ortho and para isomers
1
0%

4
6
F. Venturini et al. / Journal of Fluorine Chemistry 140 (2012) 43–48
3 3 2
Scheme 4. Radical mechanism for the addition of CF OF to aromatics in presence of CF OCF5CF as free radical activator (radical addition R).
electrostatic potential (MEP) obtained on B3LYP/6-311G** opti-
mized structures.
In the presence of a radical promoter like PMVE, CF
similarlyasintheUVlightactivatedreactions.The promoterinduces
the formation of CF O radical in steps 4A and 4B of Scheme 4.
The presence of a large excess of FTM in comparison with the
small amount of PMVE used in the free radical activated trials
assures that the alkyl radical derived from the olefin is completely
depleted in step 4B thus resulting only in a volatile perfluorinated
3
OF acts
À
Highly electron-poor substrates (atomic charge > À0.09 [e ])
3
like
a
,
a
,a
-trifluorotoluene do not react significantly in the
experimental conditions both in the electrophilic reaction or in
the radical pathway, being CF O radical also electrophilic.
3
Conversely highly electron rich aromatics (atomic
À
charge < À0.30 [e ]) like methoxybenzene show preferentially
moiety (CF
At the same time the ionic reaction in Scheme 2 is slowed down
meanwhile hydrogen abstraction is possible competitive
3 2 3
O–CF –CF ) also recognized.
an electrophilic behavior also at low temperatures as well as by
inducing the radical reaction.
a
The reaction of FTM in the experimental conditions that favor
the radical reactivity (low temperature and apolar solvent)
proceeds in such a manner to obtain both fluorobenzene and
trifluoromethoxybenzene derivatives. To account for the product
distribution, the mechanism should be at the same time ionic and
radicalic.
mechanism, especially when the hydrogen is on the benzylic
position [49].
In the experimental conditions adopted: low temperature,
apolar solvent, electron poor reagent and fast induced initiation
reaction, the free radical process, shown in steps 4C and 4D, is
favored against the electrophilic addition.
Depending on the substituent on the aromatic ring, the
mechanism and hence products can be shifted towards the
electrophilic or radical side but the product obtained is still made
of a mixture containing either the trifluoro-methoxylated and
fluoro substituted aromatics. The first explanation of this result, at
least at high conversion, is in agreement with the mechanism
proposed in the literature [49]. During the reaction, a highly polar
product, hydrogen fluoride, is accumulating in the system. The
presence of this compound could result in an ionic stabilization
thus enhancing the amount of products derived from the
electrophilic pathway (Scheme 2). The low polarity of the O–F
bond in the FTM molecule may partly take in account for the ratio
of fluorinated and trifluoromethoxylated aromatics in the electro-
philic tests since both trifluoromethoxy and fluoride ions have the
same probability to be a leaving group.
Moreover, the key step 4D – rearomatization – is a very efficient
propagation reaction generating the trifluoromethoxy compound
3 3
and CF O radicals. Since the concentration of CF OF is high, all the
electron rich carbon radicals will be easily oxidized to carboca-
tions, which will undergo a facile rearomatization [66].
3
Due to the high excess of FTM and CF O radicals in the reaction
media, the termination mechanism described in reaction 4E,
consists in the coupling of the trifluoromethoxy radicals to form
3 3
the perfluoro-di-methyl-peroxide (CF OOCF ) already observed in
similar experimental conditions [57].
Traces of polyfluorinated aromatics are visible only with
electron-rich substrates at high conversion. The ratios 2-fluor-
oanisole/2,4-difluoroanisole and 2-fluoroanisole/3,4-difluoroani-
sole do not change between electrophylic and radicalic reactions.
This finding suggests that the formation of the difluorinated
products: 2,5-difluoro-toluene, 2,4-difluoroanisole, 3,4-difluoroa-
nisole is a secondary reaction acting on the monofluorinated
aromatics formed in the electrophilic reaction.
The free radical induced mechanism operates efficiently with
toluene, benzene and chloro-benzene where the atomic charge of
those aromatics is somewhere in the middle between highly
activated and highly deactivated molecules.
Table 2
À
Atomic charges [e ] for aromatic carbon atoms estimated as the best fit to the MEP
calculated at the B3LYP/6-311G** level. The last row contains an average atomic
charge of the active sites indicated with ‘X’: position numbers 2, 4, 6 for the o,p
3 3
orienting substituents (–OCH , –CH , –Cl) and positions 3 and 5 for the meta
orienting groups (–CF ). Average atomic charge of benzene takes in account all the
3
equivalent six positions.
Ar–OCH
0.52
3
Ar–CH
0.35
3
Ar–H
Ar–Cl
Ar–CF
3
In the reaction involving electron-poor compounds like a,a,a-
X
X
X
X
X
X
trifluorotoluene the radical chain does not propagate, probably the
reaction chain formed by steps 4C and 4D is not efficient enough to
generate free radicals, therefore the amount of trifluoromethoxy-
lated product is low and comparable to the amount of PMVE
introduced. This behavior suggests that the governing reaction is
1
À0.12
À0.12
À0.11
À0.12
À0.12
À0.11
À0.12
0.07
À0.09
À0.14
À0.12
À0.14
À0.09
À0.1
À0.07
À0.08
À0.08
À0.07
À0.09
À0.08
À0.08
X
X
X
X
X
2
À0.32
À0.28
À0.09
À0.18
À0.07
À0.30
À0.25
X
X
3
À0.06
X
X
4
À0.28
5
0.02
X
X
6
À0.40
3
the hydrogen abstraction and subsequent coupling with the CF O
Average
À0.33
radical. In the case of electron-rich aromatics the experimental
conditions adopted are not sufficient to suppress the electrophilic

F. Venturini et al. / Journal of Fluorine Chemistry 140 (2012) 43–48
47
5
4
4
3
3
2
2
1
.0
.5
.0
.5
.0
.5
.0
.5
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[
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[
[
[
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Methoxybenzene
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[
[
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-0.28
-0.23
-0.18
Atomic charge
-0.13
-0.08
-0.03
(
2
Fig. 1. A predictive approach combining the (Ar–OCF
atomic charges obtained using DFT calculations. Red rhomb are referred to radical
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3
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À
À
interval À0.30 [e ] < A.C. < À0.09 [e ], show that it is possible to
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2
efficient with toluene, benzene and chloro-benzene where the
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[
[
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[
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[
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