Pentakis(trifluoromethyl)phenol from Nitrobenzene

Article abstract of DOI:10.1039/c4ra04540h

In the present work, a two step method for obtaining pentakis(trifluoromethyl)phenol from commercially available starting materials is presented. It has been prepared previously using different methods but all these methods suffer from low yields and/or t

Full text of DOI:10.1039/c4ra04540h

RSC Advances
View Article Online
View Journal | View Issue
COMMUNICATION
Pentakis(trifluoromethyl)phenol from
Nitrobenzene†‡
Cite this: RSC Adv., 2014, 4, 41895
*
Agnes Kutt and Ilmar A. Koppel
¨
Received 14th May 2014
Accepted 19th August 2014
DOI: 10.1039/c4ra04540h
www.rsc.org/advances
In the present work, a two step method for obtaining pentakis(tri- two protective ortho-CF3 groups reducing its nucleophilicity.
fluoromethyl)phenol from commercially available starting materials is Phenol 1 is a solid (m.p. 88–90 ꢀC) yet volatile substance with a
presented. It has been prepared previously using different methods recognizable smell of vanillin that makes the initial detection
but all these methods suffer from low yields and/or time-consuming simple. In the case of increased availability of phenol 1, this
purification processes. Until now, a large amount of pure pentakis- compound is envisaged to nd several useful applications.
(trifluoromethyl)phenol has been difficult to prepare. Sufficiently pure
Until now, three different methods have been published for
pentakis(trifluoromethyl)phenol is now obtained from pentaiodoni- obtaining phenol 1. None of these methods have very high
trobenzene in 58% yield and after only one time-consuming subli- yields and some of them include rather inconvenient and time-
mation process. The phenol forms during a trifluoromethylation consuming purication procedures. These methods are:13,16
reaction from pentaiodonitrobenzene; iodides are substituted by tri-
(1) Triuoromethylation of hexaiodobenzene with pregen-
fluoromethyl groups, and the nitro group is substituted by an oxygen erated CuCF3. Phenol 1 is obtained as a by-product with an
atom in the oxygen-nucleophilic environment. A small amount of approximate yield of 20%. However, on using N-methyl-2-
pentakis(trifluoromethyl)phenol is available from the authors on pyrrolidone (NMP) instead of 1,3-dimethyl-2-imidazolidinone
request.
(DMI) only traces of 1 are obtained. An increase in the forma-
tion of in DMI is related to the enhanced oxygen-
1
nucleophilicity of DMI compared to NMP. DMI has an approxi-
mately 10 times higher price than that of NMP, which makes it
almost impossible to use it in large scale triuoromethylation
reactions, where it is difficult to recover used solvents.
(2) Hydrolysis of pentakis(triuoromethyl)chlorobenzene 5,
yield 38%. The experiments were carried out by another oper-
ator, and only 17% yield was obtained aer a difficult puri-
cation process that contained several sublimation procedures,
which are very time-consuming.17 The yield probably depends
on the scale of the reaction; it is faster and simpler to sublime
smaller amounts of the product.
Phenols are very common reagents in chemistry. Tri-
uoromethylated and polyuorinated phenols are starting
materials for ethers,1 esters,2 substituted olens,3 sulfonates,4–6
sulfamates,4 etc. Alkoxy aluminates,7,8 a class of weakly coordi-
nating anions,9 are specically prepared from phenols. The
more acidic the phenol is, the weaker is the coordinating ability
of anions. Other types of coordination compounds,10 cata-
lysts,11,12 etc., for which phenols are important reagents, are
published as well.
Pentakis(triuoromethyl)phenol 1 (Scheme 1) is a very
strong acid. Its acid strength (pKa(MeCN) ¼ 10.46)13 is similar to
the acidity of picric acid (pKa(MeCN) ¼ 11.00).14,15 Pentakis(tri-
uoromethyl)phenolate 1a has well delocalized negative charge,
and the most nucleophilic site of the anion is hidden between
(3) Reaction of pentakis(triuoromethyl)benzenediazonium
+
cation C6(CF3)5N2 with water. The yield of pure 1 from
Institute of Chemistry, University of Tartu, Ravila 14A, Tartu, 50411, Estonia. E-mail:
agnes.kutt@ut.ee
† In memory of Alexander A. Kolomeitsev.
‡ Electronic supplementary information (ESI) available: Computational
coordinates and structures of compounds 2, 3, and nitrobenzene; UV-vis spectra
of 1 and 1a, 19F NMR spectra of the reactions and products; IR-ATR, GC-MS,
ESI-HRMS, and HPLC-ESI-MS spectra of products; photograph of blue N2O3 in
liquid nitrogen trap. See DOI: 10.1039/c4ra04540h
Scheme 1 Numeration of compounds.
RSC Adv., 2014, 4, 41895–41901 | 41895
This journal is © The Royal Society of Chemistry 2014

View Article Online
RSC Advances
Communication
pentakis(triuoromethyl)aniline
4
is 39%, similar to the
Formation of pentakis(triuoromethyl)phenolate 1a from
previous method and aer several sublimation procedures. The pentakis(triuoromethyl)nitrobenzene
2 appears to be a
preparation of aniline 4 from chlorobenzene 5 has a maximum nucleophilic substitution (Scheme 2). Nitrobenzene 2 is an
yield of 79%. Therefore, the yield of 1 from pentakis(tri- aromatic compound that is fully substituted by highly electro-
uoromethyl)chlorobenzene 5 is approximately 31% through negative groups – ve CF3 groups and one NO2 group make the
two steps. Chlorobenzene 5 is prepared from pentaiodo- benzene ring extremely electron decient. Thus, partial positive
chlorobenzene. The entire process takes
commercially available compounds.
4
steps from charge on the aromatic carbon atoms is high. Ipso-carbon of 2
has an especially positive partial charge and is eager to bind
In addition, phenol 1 was also prepared from pentachloro- nucleophiles. In case there are OHꢁ species, strong nucleo-
phenol and pentabromophenol by substituting chlorine or philes, in the solution of nitrobenzene 2 or nitrosobenzene 3,
bromine atoms, respectively, by CF3 groups via
a tri- then these attack the ipso-carbon, i.e. the carbon atom with the
uoromethylation method, which is also used in the present best leaving group on the molecule. Formed intermediate is
work.13 CuCF3 did not react with these substances, and it was additionally stabilized by the hyperconjugation of CF3 groups.
not possible to obtain phenol 1 using these starting materials. It Further formation includes the separation of nitrous acid HNO2
has been reported that bromo-18,19 or even chloro-substituted20,21 (or HNO in the case of nitrosobenzene 3) and phenolate 1a.
ꢁ
aromatics can be triuoromethylated using a CF3 source and HNO2 decomposes to give NO2 and NO in the solution, which
different catalytically active metals but these methods are makes the solution dark red. The fact that only one equivalent
known to be un suitable for substituting halides in electron-rich of Me4NOH is consumed to convert all the nitrobenzene 2 into
arenes.19,21
From the reaction of pentakis(triuoromethyl)benzene-
diazonium salt with dry NaNO2,16 the mixture of pentakis(tri-
uoromethyl)nitrobenzene
2 and -nitrosobenzene 3 was
obtained. It was very complicated to separate these two
compounds because of their very similar volatility and solu-
bility. When Me4NOH (20% in MeOH) was added into the NMR
tube to the mixture of compounds 2 and 3 dissolved in CDCl3,
the solution turned red in color, and the product, according to
the 19F NMR spectrum, was a single almost pure pentakis(tri-
uoromethyl)phenyl derivative (See Fig. 1 and spectrum S15 in
ESI‡). The mass-spectrometric analysis of the product that
crystallized from CDCl3 revealed that the obtained compound
was pure phenolate 1a (Spectrum S19‡).
Scheme
2 Suggested reaction pathway from nitrobenzene 2 to
phenolate 1a by a nucleophile OHꢁ.
Fig. 1 19F NMR spectra that shows how the mixture of pentakis(trifluoromethyl)nitrobenzene 2 and -nitrosobenzene 3 (ref. 16) dissolved in
CDCl3 (blue spectrum, a) are converted mainly into a single pentakis(trifluoromethyl)phenyl derivative (red spectrum, b) after treatment with
Me4NOH (25% in MeOH). ESI-HRMS measurements revealed that the compound formed is pentakis(trifluoromethyl)phenolate 1a.
41896 | RSC Adv., 2014, 4, 41895–41901
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
phenolate 1a supports the proposed mechanism shown in
The second step – triuoromethylation – is carried out in
Scheme 2.
the mixture of NMP and DMF, where CuCF3 is pregenerated
Our initial goal was to obtain pentakis(triuoromethyl) using CuBr, Ruppert–Prakash reagent and KF. The reaction
nitrobenzene known mixture is stirred overnight; during this time the mixture turns
from pentaiodonitrobenzene,22
2
a
compound, using a triuoromethylation method with pregen- dark brown, most probably from NO2. Usually it remains
erated CuCF3.13 Obtained nitrobenzene 2 would have been a lighter brown or even greenish. When the reaction is nished,
good starting material for phenol 1, aniline 4 and possibly for the solvents and other volatile materials (FSiMe3, less than ve
some other polyuorinated substances. As the result of tri- CF3-substituted nitrobenzenes, and decomposition products)
uoromethylation reaction, surprisingly, we did not get penta- are removed by vacuum distillation. Phenolate 1a is not vola-
kis(triuoromethyl)nitrobenzene 2 but only phenolate 1a. tile and remains in the residue, and is extracted from the
Additional steps are now not necessary to prepare phenol, but residue with diethyl ether. Ether is removed by rotary evapo-
unfortunately, the possibility to obtain nitrobenzene 2 in a large ration, and crude phenolate 1a (Spectrum S7‡) is sublimed
scale is also vanished. However, aniline 4 can be obtained easily from concentrated sulfuric acid. Sufficiently pure neutral
from chlorobenzene 5 with a yield of 79%. Nitrobenzene 2 can phenol 1 (Spectrum S8‡) is obtained, and no further purica-
be obtained from pentakis(triuoromethyl)benzenediazonium tion is required (Scheme 3).
salt by reacting it with NaNO2, although only at very low yield
In Scheme 4, the hypothetical reaction pathway from nitro-
(13%).16 Several nitration methods (nitric acid in the presence of benzene 2 to phenolate 1a during triuoromethylation reaction
other acids; AgNO2–BF3 system23) of pentakis(triuoromethyl) in DMF and NMP is shown. Instead of nucleophilic OHꢁ species
benzene 6 were also carried out to achieve respective nitro- (Scheme 2), basic oxygen from the solvent NMP attacks the most
benzene 2 but the efforts were unsuccessful most probably electrophilic site of the product.
because of very high positive charge on the ipso-carbon of
A blue compound is trapped into the liquid nitrogen trap
compound 6 and possibly due to steric hindrance by CF3 (Fig. S26‡) when distilling the solvents from the reaction
groups. It might be possible to obtain nitrobenzene 2 from mixture. This blue substance turns gaseous when the trap is
pentakis(triuoromethyl)benzene anion but its deprotonation warming, indicating that N2O3 (from NO2 and NO) forms in the
requires a rather strong base13 and an anhydrous oxygen free reaction. It is an additional proof to the proposed reaction
reaction environment, where it might be challenging to include mechanism in Scheme 4. Other by-products (for example 2-
a NO2+ cation.
bromo-1-methylpyrrole) were not identied.
Phenol 1 has been an oen requested compound from other
Reaction between pentaiodochlorobenzene and pregen-
research groups. The method presented here for obtaining erated CuCF3 proceeds in more predicted manner; penta-
phenol 1 with yield 58% (taking into consideration the purity of kis(triuoromethyl)chlorobenzene 5 is obtained in addition
pentaiodonitrobenzene – 57%, vide infra) proceeds via two steps to the traces of phenolate 1a and benzene 6. If we would have
starting from commercially available substances such as nitro- simple nucleophilic substitution process, then the chlorine
benzene, iodine, periodic acid, conc. H2SO4, CuBr, KF, and atom, as a better leaving group than the nitro group, would
Ruppert–Prakash reagent. The yield is still not very good but the be substituted in the same manner by the oxygen atom.
process itself is well repeatable, sufficiently pure phenol 1 is Chlorobenzene 5 is not a very good subject for hydrolysis. It
obtained (Spectra S8 and S22‡) and the yield is the largest of any appears that in addition to electronic effects there are strong
yield published so far. Whenever phenol 1 is required, this conformational effects that forces nitrobenzene
2 into
method published here would be the method of choice.
phenolate 1a.
It is known13 that pentakis(triuoromethyl)phenyl deriva-
The rst step – periodination – is carried out in conc. H2SO4
in the presence of iodine and periodic acid as described in the tives are very crowded substances. The most extreme example
ref. 22. Iodination is incomplete and the iodinated product so far is the anion of pentakis(triuoromethyꢁl)phenyl
contains pentaiodo and tetraiodo (two isomers) derivatives. malononitrile C6(CF3)5C(CN)2ꢁ, where the –C(CN)2 group
When careful recrystallization was performed (two times from needs to be planar with the benzene ring to exhibit the best
ꢁ
the mixture of benzene and ethanol),24 then pure pentaiodo- resonance properties. Because the –C(CN)2 group is quite
nitrobenzene with a yield of 22% was obtained. The chro- large and it does not t between ortho-CF3 groups quitꢁe
matographic separation of polyiodinated arenes is not trivial well, then the benzene ring of the compound C6(CF3)5C(CN)2
because of the scarce solubility and insufficient difference in takes obvious bath conformation; the angle between two
polarity to achieve separation. HPLC-ESI-MS-UV-vis analysis planes of carbon atoms of the benzene ring (one plane: ipso
showed that the crude periodinated product prepared by us
contained 31% and 12% tetraiodo derivatives and 57% pen-
taiodo derivative (Spectrum S24,‡ UV-vis measurements at
252–256 nm). Aer recrystallization, the product contained,
according to 1H NMR and HPLC-ESI-MS-UV-vis measure-
ments, mainly pentaiodonitrobenzene (Spectrum S25‡). UV-
vis peaks were identied according to the signal in ESI nega-
tive mode of an adduct of the chlorine anion and periodinated
nitrobenzene.
Scheme 3 General route from nitrobenzene to phenol 1.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 41895–41901 | 41897

View Article Online
RSC Advances
Communication
for 3. The electronic and conformational synergy in pentakis-
(triuoromethyl)nitrobenzene 2 and -nitrosobenzene 3 there-
fore makes this system sufficiently reactive to bind to nucleo-
philes; for example, nitro and nitroso groups can be detached
more simply than a chlorine atom in oxygen-nucleophilic
environment.
In the present work, we can distinguish two different tri-
uoromethylation reactions: one with pentaiodonitrobenzene
that contains up to 43% tetraiodonitrobenzenes (hereaer
indicated in the text and in ESI as the Reaction I, Spectra S2–
S8‡) and the second one with recrystallized pure pentaiodoni-
trobenzene (Reaction II, Spectra S9–S14‡).
Obtaining pure pentaiodonitrobenzene is not trivial, recrys-
tallization is carried out in rather unpleasant solvents, and the
recrystallization yield is low. It is encouraged to carry out the
triuoromethylation reaction with a mixture of pentaiodo- and
tetraiodonitrobenzenes, which is obtained from the periodina-
tion reaction because tetraiodo derivatives do not give pheno-
lates in these conditions and can be removed by vacuum
distillation with the solvents.
Aer the triuoromethylation reaction (Reaction I), the
integrals in 19F NMR spectrum show that the crude reaction
mixture contains approximately 45% phenolate 1a, 20%
symmetrical nitrobenzene 2,3,5,6-(CF3)4-C6HNO2 and 35% non-
symmetrical nitrobenzene 2,3,4,5-(CF3)4-C6HNO2 (Spectrum
S2,‡ the position of CF3 groups in the ring can be obtained from
19F coupling pattern). HPLC-ESI-MS-UV-vis results of periodi-
nated starting materials show the content to be 57, 12, 31%. It is
possible that some of the reactants are reduced during the tri-
uoromethylation reaction giving a lower content of phenolate
1a and a higher content of tetrakis(triuoromethyl)nitroben-
zenes. This similarly occurs when reacting C6I6 with CuCF3: one
of the products in addition to phenolate 1a and C6(CF3)6 was
C6(CF3)5H 6 (14% yield).13 The change in percentages in the case
of this reaction shows that approximately 12% of the pentaio-
donitrobenzene is converted into tetrakis(triuoromethyl)
nitrobenzene (mainly to the symmetrical one).
To ensure whether tetrakis(triuoromethyl)nitrobenzene
appears during the triuoromethylation process or not, a
reaction with pure pentaiodonitrobenzene was carried out
(Reaction II). Because there were some problems with cooling
during the operation, the reaction did not come out very clean.
As the result, the main component according to 19F NMR
spectrum was still phenolate 1a but there were approximately
50% of other CF3 (Spectrum S9,‡ 19F chemical shi range ꢁ45–
65 ppm) and C2F5 (ꢁ65–90 ppm) containing substances, among
which both the isomers of tetrakis(triuoromethyl)nitroben-
zenes with contents of up to 30% were present (Spectrum S10‡).
They most probably came from the reduction during the tri-
uoromethylation process. When the triuoromethylation
reaction is carried out with pentaiodochlorobenzene, hydrogen
substitutes the chlorine atom but not iodine; as a by-product we
get benzene 6 instead of tetrakis(triuoromethyl)chloroben-
zene. The yield of phenol 1 of this specic reaction from pen-
taiodonitrobenzene is 45%. The purity according to 19F NMR
and GC-MS is very high. It implies that even when extensive
Scheme
4 Possible reaction pathway from nitrobenzene 2 to
phenolate 1a by oxygen-nucleophilic solvent NMP during the tri-
fluoromethylation reaction.
and ortho carbon atoms; second plane: ortho and meta carbon
atoms on the benzene ring) is 35ꢀ (!).
A nitro group is not as large as malononitrile but it is larger
than halides. It was not possible to obtain the crystal structure
of 2 or 3 because of the extreme volatility and instability of the
crystals, even at low temperatures. Oen, computational
structure does not differ considerably from the experimental
crystal structure (Table S20‡ of ref. 13), therefore here we
examine only the computational structure of compounds 2 and
3 (pages S4–S6 in ESI‡). When the anionic malononitrile group
forces itself to be planar to the benzene ring, it is different from
nitro- and nitrosobenzene 2 and 3. The nitro group turns itself
out of plane; it is almost transverse to the benzene ring (the
angle between the RMS plane of benzene ring and the RMS
plane of ipso-C and nitro group is 79.1ꢀ), and is therefore in
lower resonance with the aromatic system. The nitroso group
also turns itself out of plane, but because it is slightly smaller
and unsymmetrical it is not that transverse to the benzene ring
(the angle between the RMS plane of benzene ring and the RMS
plane of ipso-C, N and O group is 33.6ꢀ), and the benzene ring
with CF3 groups has a denite propeller shape (Fig. 2 and pages
S4–S6 in ESI‡). Because there are no overlapped orbitals that
would strengthen the bond between the nitro group and
benzene ring in this triuoromethylated system, the distance
between ipso-C and nitrogen in compounds 2 and 3 are longer
than those for unsubstituted nitrobenzene. The values are
˚
˚
˚
1.491 A for unsubstitued nitrobenzene, 1.517 A for 2 and 1.535 A
Fig.
2 Computational geometries of unsubstituted nitrobenzene,
pentakis(trifluoromethyl)nitrobenzene 2 and pentakis(trifluoromethyl)
nitrosobenzene 3. The compounds are placed in such a manner that
the benzene ring is horizontal and the position and angle of nitro or
nitroso groups are visible.
41898 | RSC Adv., 2014, 4, 41895–41901
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
decomposition occurs, it is possible to obtain pure phenol with
reasonable yield and high purity.
Tetraiodonitrobenzenes are converted into tetrakis(tri-
uoromethyl)nitrobenzenes during triuoromethylation reac-
It would be interesting to know whether tetrakis(tri- tion. These do not further react with NMP, do not form
uoromethyl)nitrobenzene also gives phenol when reacted with phenolates and therefore can be easily separated from the
Me4NOH. On adding Me4NOH (25% in MeOH) to the distillate formed phenolate 1a. In the presence of stronger nucleophiles,
that contains isomers of tetrakis(triuoromethyl)nitroben- such as methoxide anion, pentakis(triuoromethyl)nitroben-
zenes, a dark red solution is formed indicating the formation of zenes also undergo a conversion forming either tetrakis(tri-
NO2 and NO. Later on, the distillate was further worked up, and uoromethyl)methoxybenzene or decompose giving traces of
the mixture of tetrakis(triuoromethyl)nitrobenzenes were phenolate 1a.
separated (see experimental section). We obtained a solid that
contained 51% of 2,3,4,5-(CF3)4-C6HNO2 and 49% of 2,3,5,6-
(CF3)4-C6HNO2 (according to GC-MS and 19F NMR data, Spectra
S6 and S21‡). Then, the mixture of these two substances was
Experimental section
Used chemicals
dissolved in MeOH and Me4NOH (25% in MeOH), and was
added under stirring as long as the drop of the solution did not
become red in color. MeOH was removed by rotavapor, and the
obtained solid was extracted rst with pentane and then with
chloroform. Pentane extract contains 14% of symmetrical and
86% of non-symmetrical tetrakis(triuoromethyl)phenyl
derivatives, whose chemical shis now differ from the ppm
values of initial compounds. The GC-MS revealed that these
compounds are tetrakis(triuoromethyl)methoxybenzenes
(Spectra S16 and S23‡). According to 19F NMR spectrum, chlo-
roform extract contains a small amount of pentakis(tri-
uoromethyl)phenolate 1a with other uorine containing
substances (Spectrum S17‡). ESI-HRMS shows the formation of
traces of pentakis- and tetrakis(triuoromethyl)phenolates
(Spectrum S20‡). The main quantity of the compound in the
residue from the extractions was found to be tetramethylam-
monium nitrate (IR-ATR, Spectrum S18‡).
Nitrobenzene (pure) was distilled prior to use. Almost white
colored (not green as commercial CuBr) CuBr was prepared
from CuSO4 (pure), KBr (pure) and Na2SO3 (pure) according to
ref. 25 and dried at 60 ꢀC under vacuum for 6 hours, stored and
weighted in a glovebox. H5IO6 (Sigma-Aldrich, $99.0%), I2
(99%), conc. H2SO4 (95.0–97.0%), NMP (over Molecular Sieve,
according to Karl-Fisher titration, water content 8.5 ppm), DMF
(over Molecular Sieve, according to Karl-Fisher titration, water
content 1.5 ppm), KF (spray-dried, 99%, contains 0.5% SiO2);
CF3SiMe3 ($99.0%), Me4NOH (25% in MeOH) and other
common laboratory solvents were used as received.
Methods
NMR spectra were recorded on a 200 MHz spectrometer
From this experiment, it is determined that nonsymmetrical equipped with 5 mm QNP-z probe for 19F spectra at 188.30 MHz.
tetrakis(triuoromethyl)nitrobenzene is mainly converted into Chemical shis are referenced to the internal standard C6F6
methoxybenzene, but symmetrical nitrobenzene appears to (ꢁ162.59 ppm). All the measurements were carried out at 25 ꢀC.
decompose more extensively, also giving 1a. The pathway to HRMS-ESI spectra were recorded on a FT-ICR-MS spectrometer.
2,3,5,6-(CF3)4-C6HOMe probably goes through formed tetra- Samples were dissolved in MeCN or in MeOH, and no buffer
methylammonium methoxide, which is an extremely strong solution was used. HPLC-ESI-MS-UV-vis measurements were
nucleophile that reacts with tetrakis(triuoromethyl)nitro- carried out by a device using a polar endcapped C18 analytical
benzene. The solution becomes red or brownish from formed column (4.60 mm ꢂ 250 mm, 4 mm) with C18 guard cartridge
NO2; tetramethylammonium nitrate forms when there is a small 4.0 mm ꢂ 2.0 mm. HPLC conditions were as follows: mobile
excess of Me4NOH, nitrous acid, water or oxygen in the solution. phase A: buffer solution (pH ¼ 3.2; 1 mM ammonium acetate in
0.1% formic acid); mobile phase B: methanol. The percentage of
B was linearly increased from an initial 40–100% in 20 min,
followed by 15 min at 100%. The column was maintained at 30
Conclusion
ꢀC and 20 mL of the sample was injected. Samples were dis-
Pentakis(triuoromethyl)nitrobenzene 2 and -nitrosobenzene 3 solved in MeOH. GC-MS spectra were obtained with 70 eV of
bind in oxygen-nucleophilic environment with an oxygen atom electron ionization. The GC column was 30 m long and 0.25 mm
and turn into pentakis(triuoromethyl)phenolate 1a due to the in diameter capillary column. GC program: 40–150 ꢀC: 5 ꢀC
conformational and electronic properties of the molecules. minꢁ1; 150–200 C: 10 C minꢁ1; rst 2.8 minutes was not let
Phenol 1 forms from pentaiodonitrobenzene during the tri- into mass detector. All the samples were dissolved in Et2O (1–
uoromethylation reaction with pregenerated CuCF3 in the 2% solution) and 1 mL was injected. Melting points were
solvents DMF and NMP. NMP is enough oxygen-nucleophilic determined with capillary melting point apparatus and are
that the conversion occurs during the triuoromethylation uncorrected. To prevent sublimation during the melting
reaction. Some of the reactants reduce during tri- procedure the capillaries were sealed before measurements.
uoromethylation reaction giving tetrakis(triuoromethyl) Computations were carried out by Turbomole 6.5. Geometry
nitrobenzene but not pentakis(triuoromethyl)benzene, as optimization was carried out using def-TVZP basis set. Obtained
typically obtained in triuoromethylation reactions with pen- coordinates and values of energy for molecules are presented in
ꢀ
ꢀ
taiodochlorobenzene or hexaiodobenzene.
ESI.‡
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 41895–41901 | 41899

View Article Online
RSC Advances
Communication
ether has to be removed carefully to prevent bubbling of the
solution.
Pentaiodonitrobenzene C6I5NO2
The reaction was carried out, as reported in ref. 22. Periodic acid
(23.85 g, 0.10 mol) was dissolved in conc. sulfuric acid (375 mL).
Pounded iodine (78.00 g, 0.30 mol) was added to the clear
solution, and then stirred using an overhead stirrer for half an
hour. The reaction mixture was then placed in an ice-bath.
Distilled nitrobenzene (7.0 mL, 0.067 mol) was added over 15
minutes. The mixture was then stirred for one day at room
temperature and then for one day at 95 ꢀC. Aer heating the
Phenol 1 obtained aer sublimation is slightly hygroscopic;
therefore, let the sublimation nger to warm up before scraping
off the product. Yield from pentaiodonitrobenzene (it has been
taken into account the content of tetraiodo nitrobenzenes from
HPLC-UV-vis measurements – 57%) of phenol 1 is 58% (1.45 g,
0.003 mol). M.p. 88–90 C (lit. 88–90 C)13,16
ꢀ
ꢀ
19F NMR spectrum of crude reaction mixture (Reaction I,
Spectrum S2‡) shows that there are 64% 2,3,4,5-(CF3)4-C6HNO2
and 36% 2,3,5,6-(CF3)4-C6HNO2 (percentages are converted to
100% leaving out 1a). Aer distillation, according to 19F NMR
spectrum, the ratio is changed to 54 and 46%, respectively
(Spectrum S3‡). The content of symmetrical nitrobenzene has
increased. There were no considerable amounts of 2,3,4,5-
(CF3)4-C6HNO2 in the cold-trap. It is possible that some of the
CF3 substituted nitrobenzene decomposed during the
distillation.
ꢀ
reaction mixture to 95 C for one day, the iodine sublimed on
the top of the ask. The solution was then carefully poured onto
ice. The yellow suspension was then ltered. The residue was
not washed with ethanol as described in ref. 22 because the
product is soluble in this solvent. Pentaiodonitrobenzene on
the lter was instead recrystallized using a continuous extractor
(Soxhlet extractor may be used as well) from AcOEt (400 mL).
One batch of the product was ltered. The volume of the AcOEt
was then reduced to 200 mL and the solution was placed into
refrigerator. The yellow precipitate obtained was ltered again,
the two batches were combined, washed with hexane (200 mL)
and dried in a vacuum (10ꢁ3 Torr) at 50 ꢀC for six hours. 36.4 g
of a mixture of penta- (57%) and tetraiodonitrobenzenes (43%)
was obtained.
The distillate was worked up as follows: water (25 mL)
was added to the distillate (100 mL) and extracted with pentane
(3 ꢂ 50 mL). Pentane was removed by rotary evaporation; and
the ask was kept cold to prevent the sublimation of
compounds. To the obtained oily substance, 2 mL of water was
added, and crystals formed into this solution. The solution was
ltered and the solid on the lter was recrystallized from
pentane (25 mL). The obtained solid is the mixture of 2,3,4,5-
(CF3)4-C6HNO2 (51%) and 2,3,5,6-(CF3)4-C6HNO2 (49%) (Spectra
S6 and S21‡).
According to the 1H NMR spectrum and HPLC-ESI-MS-UV-vis
measurements, recrystallization twice from benzene and
ethanol24 gave the substance that has no aromatic hydrogens.
The recrystallization yield was 22%.
Acknowledgements
Pentakis(triuoromethyl)phenol C6(CF3)5OH 1
The reaction was carried out as described for C6I5Cl in ref. 16. This study was supported by the Estonian Science Foundation
Instead of C6I5Cl, C6I5NO2 (may contain C6I4HNO2 derivatives) (grants nos 8720 and 8162), the Estonian Research Council
was used: Dispersion of CuBr (9.71 g, 0.050 mol) and DMF (grant no. PUT182), the targeted nancing project of the Esto-
(50 mL) was cooled to 0 ꢀC, triuoromethyltrimethylsilane (9.50 nian Ministry of Education and Science (grant no. SF0180089
mL, 0.067 mol) was added. Aer that, KF (3.86 g, 0.066 mol) was s08), the Estonian Centre of Excellence (HIGH-TECHMAT
added slowly via solid addition funnel. Then, NMP (10 mL) was SLOKT117T) and by the Estonian National R & D infrastruc-
included, and the reaction mixture was stirred on a ice-bath for ture development program of Measure 2.3 “Promotion of
1.5–2 hours to form active CuCF3. C6I5NO2 (7.70 g, contains development activities and innovation” (Regulation no. 34)
0.006 mol pentaiodonitrobenzene, and 0.005 mol isomers of funded by the Enterprise Estonia foundation.
tetraiodonitrobenzenes) and additional NMP (40 mL) was
added. The reaction mixture was stirred overnight, and solvents
with other volatile substances were distilled off. The residue
References
contains phenolate 1a, which is further worked up. It is
important to remove the high boiling solvents as much as
possible from the residue to simplify the following workup. It
helps if the residue is also washed with pentane to remove
solvents but not phenolate 1a. Phenolate 1a was then extracted
into diethyl ether (3 ꢂ 70 mL). Ether was evaporated, the
obtained solid was transferred into sublimation apparatus,
conc. H2SO4 (8 mL) was added and phenol 1 sublimed at
1 V. V. Aksenov, V. M. Vlasov and G. G. Yakobson, J. Fluorine
Chem., 1982, 20, 439–458.
2 M. H. Emmert, A. K. Cook, Y. J. Xie and M. S. Sanford, Angew.
Chem., Int. Ed., 2011, 50, 9409–9412.
3 Z. Ke and Y.-Y. Yeung, Org. Lett., 2013, 15, 1906–1909.
4 T. Agrawal and S. P. Cook, Org. Lett., 2013, 15, 96–99.
5 C. B. Bheeter, J. K. Bera and H. Douceta, Adv. Synth. Catal.,
2012, 354, 3533–3538.
6 J. W. W. Chang, E. C. Chia, C. L. L. Chaia and J. Seayad, Org.
Biomol. Chem., 2012, 10, 2289–2299.
ꢀ
60–70 C at static vacuum (4–5 Torr).
If the residue contains NMP or DMF aer distillation, it is
not possible to solidify the product aer removing ether; an oily
substance is obtained instead, which has to be transferred into
the sublimation apparatus by dissolving it in a small amount of
ether. Prior to the addition of conc. H2SO4 and sublimation,
7 I. Krossing, H. Brands, R. Feuerhake and S. Koenig, J.
Fluorine Chem., 2001, 112, 83–90.
8 M. V. Metz, Y. Sun, C. L. Stern and T. J. Marks,
Organometallics, 2002, 21, 3691–3702.
41900 | RSC Adv., 2014, 4, 41895–41901
This journal is © The Royal Society of Chemistry 2014

View Article Online
Communication
RSC Advances
¨
9 I. Krossing and I. Raabe, Angew. Chem., Int. Ed., 2004, 43, 16 A. Kutt, F. Werner, I. Kaljurand, I. Leito and I. A. Koppel,
2066–2090. ChemPlusChem, 2013, 78, 932–936.
10 M. V. Petersen, A. H. Iqbal, L. N. Zakharov, A. L. Rheingold 17 Large amount of C6(CF3)5OLi (lithium salt of 1a) was
and L. H. Doerrer, Polyhedron, 2013, 52, 276–283.
11 R. C. Neu, Y. Ouyang, S. J. Geier, X. Zhao, A. Ramos and
D. W. Stephan, Dalton Trans., 2010, 39, 4285–4294.
prepared according to method 2 in the main text for
electrochemical measurements by another research group.
No data has been published.
12 N. Ibrahim, M. H. Vilhelmsen, M. Pernpointner, 18 S. Roy, B. T. Gregg, G. W. Gribble, V.-D. Le and S. Roy,
F. Rominger and A. S. K. Hashmi, Organometallics, 2013,
32, 2576–2583.
Tetrahedron, 2011, 67, 2161–2195.
19 H. Morimoto, T. Tsubogo, N. D. Litvinas and J. F. Hartwig,
Angew. Chem., Int. Ed., 2011, 50, 3793–3798.
¨
13 A. Kutt, V. Movchun, T. Rodima, T. Dansauer, E. B. Rusanov,
I. Leito, I. Kaljurand, J. Koppel, V. Pihl, I. Koppel, 20 E. J. Cho, T. D. Senecal, T. Kinzel, Y. Zhang, D. A. Watson and
G. Ovsjannikov, L. Toom, M. Mishima, M. Medebielle, S. L. Buchwald, Science, 2010, 328, 1679–1681.
¨
¨
E. Lork, G.-V. Roschenthaler, I. A. Koppel and 21 T. Knauber, F. Arikan, G.-V. Roschenthaler and L. J. Gooßen,
A. A. Kolomeitsev, J. Org. Chem., 2008, 73, 2607–2620. Chem.–Eur. J., 2011, 17, 2689–2697.
¨
¨
14 A. Kutt, T. Rodima, J. Saame, E. Raamat, V. Maemets, 22 D. L. Mattern, J. Org. Chem., 1984, 49, 3051–3053.
I. Kaljurand, I. A. Koppel, R. Y. Garlyauskayte, 23 G. A. Olah, A. P. Fung, S. C. Narang and J. A. Olah, J. Org.
Y. L. Yagupolskii, L. M. Yagupolskii, E. Bernhardt,
Chem., 1981, 46, 3533–3537.
H. Willner and I. Leito, J. Org. Chem., 2011, 76, 391–395.
24 G. B. Deacon and G. J. Farquharson, Aust. J. Chem., 1977, 30,
1701–1713.
¨
¨
15 A. Kutt, I. Leito, I. Kaljurand, L. Soovali, V. M. Vlasov,
L. M. Yagupolskii and I. A. Koppel, J. Org. Chem., 2006, 71, 25 L. Hartwell, Org. Synth., 1955, 3, 185–188; L. Hartwell, Org.
2829–2838.
Synth., 1944, 24, 22–25.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 41895–41901 | 41901