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DOI: 10.1002/cplu.201300160
Pentakis(trifluoromethyl)benzenediazonium Cation: A
Useful Building Block for the Syntheis of Trifluoromethyl-
Substituted Derivatives
Agnes Kꢀtt,*[a] Franz Werner,[b] Ivari Kaljurand,[a] Ivo Leito,[a] and Ilmar A. Koppel[a]
In memory of Detlef Schrçder
Diazonium compounds,[1] known for more than two hundred
years, have been very useful intermediates for synthesizing
common chemicals[2] such as alcohols, halides,[3] sulfochlorides,
and azo dyes.[4] Arenediazonium compounds, next to halides,
are often used to produce aryl radicals,[5,2] which are intermedi-
ates for various amino acids,[6] pharmaceuticals,[7] heterocy-
cles,[8] arylolefins,[9] biaryls,[10,11] and other useful materials.[12]
Arenediazonium compounds are also useful in organometal-
lic[13] and bioorganic chemistry,[14] and in materials science,[15]
nanotechnology,[16] drug synthesis.[16c,17]
zene using liquid ammonia. Here, NaNH2 in dry tetrahydrofuran
was used to convert substituted chlorobenzene 3 into aniline
2 with 66–79% yield. For this process, at least two equivalents
of NaNH2 were used, and although the acidity of 2 is quite
high (pKa in acetonitrile (MeCN) is 24.59,[23] that is, only by
1 pKa unit weaker than acetic acid[24]), instead of Na salt, un-
charged aniline 2 was obtained. The mechanism of the reac-
tion is either an addition/elimination of nucleophilic aromatic
substitution SNAr or unimolecular radical nucleophilic substitu-
À
tion SRN1.[25] The NH2 ion is a very strong nucleophile. Chloro-
Trifluoromethyl-substituted aromatic compounds[18] have
gained much importance in drug discovery and synthesis of
pharmaceutical agents, agrochemicals, and various types of or-
ganic materials.[19] They have been used to stabilize many oth-
erwise reactive species such as free radicals,[19,20] carbenes,[21]
and carbenoids.[22] Pentakis(trifluoromethyl)phenyl (C6(CF3)5)
derivatives occupy a special place among CF3-substituted aro-
matics. The C6(CF3)5 derivatives have been shown to exhibit
unique characteristics—the ability to delocalize negative
charge, large molecular weight yet high volatility, distorted
benzene ring, exceptional steric hindrance, and more. Howev-
er, until now, only a few types of C6(CF3)5 derivatives have
been prepared.[23]
benzene 3 has plenty of electron-withdrawing groups, and the
reaction took place at room temperature with a good yield. In
a previously published method,[23] liquid ammonia was used to
prepare aniline 2 from chlorobenzene 3. The reaction was car-
ried out in a sealed reaction tube under high pressure, which
is potentially dangerous and requires special glassware. In ad-
dition, the yield of 2 from 3 using liquid ammonia was rather
low (28%), as speculated, because of aminolysis of the para-
and ortho-CF3 groups into CN groups. The reaction described
here makes aniline 2 more conveniently available in laborato-
ries.
The main by-product of the amination reaction with NaNH2
is C6(CF3)5H 6 (15–20%), which might derive from the metalla-
tion of chlorobenzene 3 (the same way iodides give organo-
metallates) to yield reduced product 6 after protonation (with
protic solvents or impurities). According to the ESI-MS meas-
urements, substituted phenolate 4À, pentakis(trifluoromethyl)-
Herein, we present the synthesis of pentakis(trifluorome-
À
thyl)benzenediazonium cation (1 as a BF4 salt), which is ex-
pected to be a useful building block for obtaining different
types of C6(CF3)5 compounds and makes this structural frag-
ment more accessible for various applications. Pentakis(trifluor-
omethyl)phenol 4, -iodobenzene 5, -chlorobenzene 3, and -ni-
trobenzene 7, were obtained from their corresponding diazoni-
um cations. As by-products, pentakis(trifluoromethyl)nitroso-
benzene 8 and pentakis(trifluoromethyl)benzene 6 were also
formed (Scheme 1).
cyclopentadienide,
and
bis[pentakis(trifluoromethyl)-
phenyl]amide were also produced during the amination reac-
tion. Aniline 2 and reduction product 6 were separated from
these salts by extraction with pentane because of their very
good solubility in apolar solvents and purified either by subli-
mation or column chromatography (see the Supporting Infor-
mation for reaction details).
Laboratory synthesis of ring-substituted anilines often pro-
ceeds via nitrobenzene (reduction) or phenol, or via chloroben-
Pentakis(trifluoromethyl)chlorobenzene 3 was prepared from
pentaiodochlorobenzene[26] and in situ pregenerated (trifluoro-
methyl)copper (CuCF3) as published previously (see the Sup-
porting Information for reaction details).[23] Diazonium salt 1,
with yield 49%, was prepared from aniline 2 using NOBF4 in
dry MeCN and precipitated with dichloromethane as previously
described.[11] During diazotization, phenol 4 (19%) appeared in
the reaction mixture most of the time, which indicated the
high reactivity of diazonium salt 1 with water derived from the
reaction itself and the moisture in the solvents. At the same
time, crystals of 1 could be isolated. The crystals were stable
[a] Dr. A. Kꢀtt, Dr. I. Kaljurand, Prof. I. Leito, Prof. I. A. Koppel
Institute of Chemistry
University of Tartu
14A Ravila Street, Tartu, 50411 (Estonia)
[b] Dr. F. Werner
Department of Chemistry
Tallinn University of Technology
15 Akadeemia tee, 12618, Tallinn (Estonia)
Supporting information for this article is available on the WWW under
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemPlusChem 2013, 78, 932 – 936 932