Generation of heteroarylium-N-difluoromethylides and heteroaryl-N-difluoromethyl anions and their reactions with electrophiles: Heteroaryl- and heteroarylium-N-difluoromethyl trimethylsilanes and a new heteroaryl-N-trifluoromethane

Article abstract of DOI:10.1016/S0022-1139(01)00390-6

Reductive debromination of N-bromodifluoromethyl-4-dimethylaminopyridinium bromide, 1-bromodifluoromethyl-imidazole, 1-methyl-3-bromodifluoromethyl-imidazolium bromide and 1-bromodifluoromethyl-2-methyl-benzimidazole using tetrakis(dimethylamino)ethylene (TDAE) or tris(diethylamido)phosphite leads to new fluorinated carbanionic species, namely heteroarylium-N-difluoromethylides and heteroaryl-N-difluoromethyl anions. In the presence of electrophiles such as benzaldehyde, chlorodiphenylphosphine and chlorotrimethylsilane, the corresponding heteroarylium- and heteroaryl-N-difluoromethylated derivatives, imidazole-N-difluoromethyl-phosphines and -silanes, 2-methyl-benzimidazole-N-difluoromethyltrimethyl-carbinols-phosphines and -silanes were obtained. Similar 4-dimethylaminopyridinium derivatives were synthesized.

Full text of DOI:10.1016/S0022-1139(01)00390-6

Journal of Fluorine Chemistry 109 42001) 173±181
Generation of heteroarylium-N-di¯uoromethylides and
heteroaryl-N-di¯uoromethyl anions and their reactions with
electrophiles: heteroaryl- and heteroarylium-N-di¯uoromethyl
trimethylsilanes and a new heteroaryl-N-tri¯uoromethane
a
German Bissky , Gerd-Volker Roschenthaler , Enno Lork , Jan Barten ,
a,*
a
a
È
Maurice Medebielle , Vasilij Staninets , Alexander A. Kolomeitsev
b,1
c
c,*
Â
aInstitute of Inorganic and Physical Chemistry, University of Bremen, Leobener Strasse, 28334Bremen, Germany
b
 Â
Electrochimie Moleculaire, Universite Paris7-Denis Diderot, UMR CNRS 7591, Case Courrier 7107,
2 place Jussieu, F-75251 Paris Cedex 05, France
cInstitute of Organic Chemistry, Ukrainian Academy of Sciences, Murmanskaya 5, 02094Kiev, Ukraine
Received 3 January 2001; accepted 6 March 2001
Abstract
Reductive debromination of N-bromodi¯uoromethyl-4-dimethylaminopyridinium bromide, 1-bromodi¯uoromethyl-imidazole, 1-methyl-
3-bromodi¯uoromethyl-imidazolium bromide and 1-bromodi¯uoromethyl-2-methyl-benzimidazole using tetrakis4dimethylamino)ethylene
4TDAE) or tris4diethylamido)phosphite leads to new ¯uorinated carbanionic species, namely heteroarylium-N-di¯uoromethylides and
heteroaryl-N-di¯uoromethyl anions. In the presence of electrophiles such as benzaldehyde, chlorodiphenylphosphine and chlorotri-
methylsilane, the corresponding heteroarylium- and heteroaryl-N-di¯uoromethylated derivatives, imidazole-N-di¯uoromethyl-phosphines
and -silanes, 2-methyl-benzimidazole-N-di¯uoromethyltrimethyl-carbinols-phosphines and -silanes were obtained. Similar 4-dimethyla-
minopyridinium derivatives were synthesized. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: Imidazole-N-di¯uoromethyltrimethyl-silane; 1-Di¯uoromethyltrimethylsilyl-pyridinium tri¯ate; N-di¯uoromethylide; N-tri¯uoromethyl-imida-
zole
1. Introduction
derivatives play a rising role in synthesis of geminal di¯uor-
omethylene compounds with a broad spectrum of biological
activity [1±9]. In contrast to the extensively investigated
chemistry of the aforementioned derivatives, little is known
about heteroaryl-N-di¯uoromethyl anions, heteroarylium-
N-di¯uoromethylides or their trimethylsilyl derivatives.
Introduction of the heteroaryl-N-di¯uoromethyl moiety into
organic or organoelement compounds may induce new
interesting biological properties. Just recently tetrakis4di-
methylamino)ethylene 4TDAE) was successfully applied for
the generation of heteroaryl-C-di¯uoromethylanions and
heteroaryldi¯uoromethylation of carbonyl compounds
[10,11] and for the synthesis of potent non-nucleosidic
HIV-1 reverse transcriptase inhibitors 4NNRTIs) [12].
Searching for synthetic methods for heteroaryl-N-di¯uor-
omethyl-anions we decided to broaden our study on the
catalytic N-bromodi¯uoromethylation of 4-dimethylamino-
pyridine, which resulted in the synthesis of the ®rst N-
bromodi¯uoromethylated heterocyclic compounds [10±13],
Recently, the introduction of the di¯uoromethylene moi-
ety into organic compounds has attracted much attention
due to the biological properties exhibited by gem-di¯uoro
compounds as compared to their non-¯uorinated analogs
[1±3]. Among various methods for the synthesis of such
compounds, the transformations of nucleophilic di¯uoro-
methylene synthons, i.e. 1,1-4di¯uoroalkyl)silanes, di¯uor-
oenoxysilanes, carbalkoxydi¯uoromethylene and dialkoxy
phosphinyldi¯uoromethylene zinc, copper and silicon
* Corresponding authors. Fax: ‡49-421-218-4267.
È
E-mail addresses: gvr@chemie.uni-bremen.de 4G.-V. Roschenthaler),
alexechemie.uni-bremen.de 4AlexA. Kolomeitsev).
1
Á Á
Co-corresponding author. Present address: Synthese, Electrosynthese
Â
Â
Â
Â
Â
et Reactivite des Composes Organiques Fluores, Universite Claude
Bernard-Lyon1, UMR CNRS 5622, 43 Bd du 11 Novembre 1918,
F-69622 Villeurbanne Cedex.
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 4 0 1 ) 0 0 3 9 0 - 6

174
G. Bissky et al. / Journal of Fluorine Chemistry 109 92001) 173±181
where a chain carbenic mechanism involving a 4-dimethy-
laminopyridinium di¯uoromethylide intermediate was pro-
posed for the reaction with CF2Br2, in contrast to a radical
pathway for BrCF2CF2Br [13]. To the best of our knowl-
edge, it was the ®rst indication of the generation and
participation of a nitrogen di¯uoromethylide in the reaction
[14±16]. Iminiodi¯uoromethanides formed by the reaction
of di¯uorocarbene 4from CF2Br2 and excess of lead powder
in the presence of Bu4NBr) with benzaldehyde and benzo-
phenone imines underwent regioselective 1,3-dipolar
cycloaddition to aldehydes giving oxazolidine derivatives
[16,17]. N-methylides including pyridinium-N-dichloro-
methylide are of considerable importance for stereoselective
synthesis of heterocycles via 1,3-cycloaddition reactions
with electron de®cient alkenes and alkynes [18±20]. More-
over, N-bromodi¯uoromethylated heterocycles are useful
precursors for N-tri¯uoromethylated derivatives [10]. There
is a growing interest for N-per¯uoroalkylated heterocyclic
systems, e.g. 44-chloro-benzyl)-42-chloro-9-tri¯uoromethyl-
9H-purin-6-yl)-amine being an inhibitor of cyclin dependent
kinase 2 [21].
observed for the monobromodi¯uoromethylated compound,
the second reduction step corresponds to the reduction of the
±NCF2CF2H pyridinium derivative. These studies indicate
that the cleavage of the C±Br bonds is relatively easy
4positive reduction potentials) and, therefore, electron trans-
fer reactions using the TDAE as reductive reagent should be
conceptually feasible, as already demonstrated in our earlier
work [7,8].
2.2. Generation and reactions of heteroarylium-N-
difluoromethylides
4-Dimethylamino-pyridinium-N-di¯uoromethylide 4A)
was generated in situ using TDAE and trapped in the
presence of the electrophile. With benzaldehyde as a solvent
1-41,1-di¯uoro-2-hydroxy-2-phenyl-ethyl)-4-dimethyla-
mino-pyridinium bromide 42) was obtained in 46% isolated
yield 488% 19F NMR). Chlorodiphenyl phosphine and chlor-
otrimethylsilane were able to trap intermediate A followed
by the exchange of chloride for tri¯ate as counterion provid-
ing water soluble 1-4di¯uoro-diphenylphosphanyl-methyl)-
4-dimethylamino-pyridinium tri¯ate 43) 467%) and 1-
4di¯uoro-trimethylsilyl-methyl)-4-dimethylamino-pyridi-
nium tri¯ate 44) 453%), which reacted with benzaldehyde to
give tetramethylammonium 1-41,1-di¯uoro-2-phenyl-ethy-
lat)-4-dimethylamino-pyridinium tri¯ate 45) and trimethyl-
¯uorosilane when using a stoichiometric amount of
tetramethylammonium ¯uoride. In solvents like CH2Cl2
or CH3CN compound 1 and excess of TDAE react rapidly
and exothermally to give the corresponding N-di¯uoro-
methyl derivative, 1-di¯uoro-methyl-4-dimethylamino-pyr-
idinium bromide [10], as the only ¯uorinated product
4Scheme 1, presenting only the quinoidal mesomeric form
[10] of the heterocycle).
2. Results and discussion
2.1. Electrochemistry
Some of the derivatives synthesized in this work have
been studied by cyclic voltammetry, in acetonitrile 4CH3CN)
and N,N-dimethylformamide 4DMF) as solvent with
NBu4PF6 as supporting electrolyte. The reduction potentials
of the halogenodi¯uoro-methylated compounds were mea-
sured, in order to establish their ability to be involved in
single electron transfer reactions of synthetic utility. Cyclic
voltammetry of the 4-dimethylamino-pyridinium-N-bromo-
di¯uoromethyl bromide 41) shows two irreversible reduction
steps in CH3CN or DMF at respective potentials close to
À0.89 and À1.54 V versus saturated calomel electrode
4SCE; peak potentials at 0.2 V/s on a glassy carbon elec-
trode). The ®rst reduction step corresponds to the uptake of
1.6 electrons 4as compared to the one-electron oxidation
wave of ferrocene) and to the cleavage of the carbon±
bromine bond and the second reduction step, located at a
more negative potential, corresponds to the reduction of the
4-dimethylamino-pyridinium-N-di¯uoromethyl bromide, as
was shown with comparison to an authentic sample 4peak
potential at 0.2 V/s ˆ À1:55 V versus SCE). This was also
con®rmed by a preparative electrolysis in CH3CN contain-
ing 0.1 M Bu4NPF6, at a carbon felt cathode, at a potential
close to À0.92 V versus SCE giving after consuming close
to 1.5 F/mol of starting material, a major product identi®ed
as the 4-dimethylamino-pyridinium-N-di¯uoromethyl
2.3. Synthesis of the N-bromodifluoromethyl
heterocycles
Deprotonation of imidazoles 6a,b with potassium tert-
butylate followed by the reaction with dibromodi¯uoro-
methane produces N-bromodi¯uoromethyl imidazoles
8a,b. This method provides an important possibility to
generate a bromodi¯uoromethyl fragment at the heterocyc-
lic nitrogen, contrary to previous reports on the interaction
of the imidazolyl anion with CF3Br or RFI leading only to a
mixture of 2- and 4-per¯uoroalkyl substituted imidazoles
without N-per¯uoroalkylation [22]. One might anticipate a
halogenophilic reaction of the imidazolyl anion 7a with
CF2Br2 generating an imidazole-N-di¯uoromethyl anion
succeeded by the formation of 1-bromodi¯uoromethyl-imi-
dazole 48a) similarly to the interaction of dihalodi¯uoro-
methane with PhOÀ and PhSÀ [23] 4Scheme 2).
2
bromide [19F NMR: dF ˆ À94:9 4d, JHF ˆ 58:0 Hz)].
Surprisingly, the counterion of the imidazolyl anion dras-
‡ ‡
The reduction of 4-dimethylammonium-pyridinium-N-
CF2CF2Br bromide occurs at more negative potentials close
to À1.18 V versus SCE and À1.42 V versus SCE. As
tically in¯uenced the reaction with CF2Br2, with Li or Na
the reaction proceeded slowly at room temperature and was
accelerated by a small quantity of Zn powder which also

G. Bissky et al. / Journal of Fluorine Chemistry 109 92001) 173±181
175
Scheme 1.
2.4. Generation of heteroaryl-N-difluoromethyl
anions and their derivatives
The imidazol-N-di¯uoromethyl anion 4B) and 2-methyl-
1-di¯uoromethyl-benzimidazole anion had to be generated
in situ from 1-bromodi¯uoromethyl-imidazole 48a) [26], 1-
di¯uoromethyl-2-phenyl-imidazole 48b) [26] and 1-di¯uor-
omethyl-2-methyl-benzimidazole 411) [24] using tris4-
Scheme 2.
diethylamino)phosphine
under
Marchenko±Ruppert
increases the amount of the 1-di¯uoromethyl-imidazole by-
product, e.g. 2-methyl-benzimidazolyl sodium reacts with
200% excess of CF2Br2 4THF, 208C, 2d) to afford 1-bro-
modi¯uoromethyl-2-methylbenzimidazole 411) in 12% iso-
lated yield. This reaction under the same conditions in
acetonitrile gave 32% 19F NMR yield. When this work
was in progress, brief communications describing a synth-
esis of N-bromodi¯uoromethylated benzimidazole deriva-
tives and N-bromodi¯uoromethyl imidazole under reaction
conditions mentioned in our previous publication [10] was
published [24,25], where, contrary to our work, the yield of
8a and 11 have been reported to be 9 and 46%, respectively,
using zinc as a catalyst and sodium salts of imidazole and 2-
methylbenzimidazole in acetonitrile. At room temperature
without a catalyst in our case, the reaction of CF2Br2 with
imidazolyl potassium 47a) and 2-methyl-benzimidazolyl
potassium 410) lead to 8a in 43% yield 42d, THF), in
71% yield 412 h, DMF) and 11 in 70% yield 4DMF),
respectively. Only negligible amounts 41 mol%) of N-
di¯uoromethylated heterocyles were obtained 4Scheme 3).
reaction conditions [27,28] 4Schemes 4 and 5) and trapped
in the presence of the appropriate electrophile, namely,
benzaldehyde, chlorotrimethylsilane and chlorodiphenyl-
phosphine 4Scheme 4).
In the presence of a 10-fold excess of Me3SiCl in
CH2Cl2 at À708C, the reaction yielded imidazol-1-yl-
di¯uoromethyltrimethylsilane 412a), 2-phenyl-imidazole-
1-yl-di¯uoromethyl-trimethylsilane 412b) and 2-methyl-
benzimidazole-1-yl-di¯uoromethyl trimethylsilane 420)
4Scheme 5) in 85, 75 and 82%, isolated yields, respectively
[26]. These compounds have been easily prepared with
aluminium powder and one-fold excess of chlorotrimethyl-
silane in monoglyme or N-methyl-pyrrolidone [29], in 71,
75 and 73% yields, respectively. They, in the presence of a
catalytic amount of ¯uoride, formed imidazol-1-di¯uoro-
methyl anions which could be trapped with benzaldehyde to
give the 1-41,1-di¯uoro-2-phenyl-2-trimethylsiloxy-ethyl)-
imidazoles 414a,b). Compound 14b, after hydrolysis
furnished the corresponding alcohol 15b 4Scheme 4). The
reactions of heteroaryl-N-di¯uoromethyltrimethylsilanes
Scheme 3.

176
G. Bissky et al. / Journal of Fluorine Chemistry 109 92001) 173±181
Scheme 4.
with enolizable ketones, e.g. cyclohexanone, was successful
with a stoichiometrical amount of tetramethylammonium
¯uoride. In contrast to tri¯uoromethyltrimethylsilane,
CF2 ˆ CFSiMe3, 4EtO)24O)PCF2SiMe3 and C6F5SiMe3
give carbanion addition products only with aldehydes, with
enolizable ketones, silylated enols only [30±32]. All these
reactions proceed using ¯uoride ion catalysis. If only
1 mol% of Me4NF or KF was added to the silane mono-
glyme solution of 12b and cyclohexanone at either 08C or at
ambient temperature, the main reaction product formed was
1-di¯uoromethyl-2-phenyl-imidazole 419b) 499%). The tar-
get 1-42-phenyl-imidazol-1-yl-1,1-di¯uoromethyl)-1-cyclo-
hexanol 416b) was observed only as an impurity 41%) in the
19F NMR spectrum. Whereas an equimolar amount of
Me4NF favors the formation of the carbanion addition
product and after hydrolysis 16b was obtained in 64%
470% 19F NMR) yield, a one-fold excess of cyclohexanone
improves the yield to 77% 483% 19F NMR) 4Scheme 4).
Hydrolysis of 1-41,1-di¯uoro-2-phenyl-2-trimethylsi-
loxy-ethyl)-2-methyl-benzimidazole yielded 2-42-methyl-
benzimidazole)-1-yl-2,2-di¯uoro-1-phenyl-ethanol
421)
481% yield). In addition, the 1-di¯uoromethyl-2-methyl-
benzimidazole anion could be produced by reductive deb-
romination of 11 [24] using TDAE in benzaldehyde as a
solvent to give 2-42-methyl-benzimidazole)-1-yl-2,2-
di¯uoro-1-phenyl-ethanol 421) 4Scheme 5).
Obviously, the electron withdrawing effect of the hetero-
cyclic nuclei rendered the heteroaryl-N-CF2 substituted
alcohols stable towards hydrolysis, unlike compounds
containing the Alk2NCF2 moiety which proved to be
soft ¯uorinating agents for the substitution of alco-
holic hydroxy groups [33]. 1-41,1-Di¯uoro-2-hydroxy-2-
phenyl-ethyl)-3,3-diphenyl-aziridine-2-carboxylic
acid
ethyl ester, the only example of a heteroaryl-N-di¯uoro-
methyl carbinol was recently isolated in 5% yield from a
complex mixture resulting from the reaction of the corre-
sponding iminiodi¯uoromethylide with benzaldehyde [16].
Anionic imidazole-N-di¯uoromethylation of Ph2PCl furn-
ished imidazol-1-yl-di¯uoromethyl diphenylphosphine
417a) 478% yield) 4Scheme 5). Compound 8a was success-
fully ¯uorinated using antimony tri¯uoride to furnish 1-
tri¯uoromethylimidazole 418a). 1-Di¯uoromethylimidazole
419a) 4Scheme 4) or 1-di¯uoromethyl-2-methyl-
benzimidazole 422) could be obtained in 95% yield by
reduction of N-bromodi¯uoromethyl derivatives with Zn
Scheme 5.

G. Bissky et al. / Journal of Fluorine Chemistry 109 92001) 173±181
177
2.6. Heteroarylium-N-difluoromethylides
Similarly to DMAP [10,11], 1-methyl-imidazole 423a)
reacted rapidly with dibromodi¯uoromethane in CH3CN
under TDAE, Zn or Cu powder catalysis [13] to yield 1-
methyl-3-bromodi¯uoromethyl-imidazolium bromide 424a-
Br) 475% isolated yield). Similar tri¯ate salts 24a,b-OTf
have been prepared in 100% yield by bromodi¯uoromethy-
lation of imidazoles 6a,b followed by methylation in the
3-position using methyl tri¯ate. 3-Methyl-imidazolium-N-
di¯uoromethylide generated from 1-methyl-3-bromodi-
¯uoromethyl-imidazolium tri¯ate 424-Otf) in the presence
of TDAE reacted with benzaldehyde like 4-dimethylamino-
pyridinium-N-di¯uoromethylide. After hydrolysis 1-41,1-
di¯uoro-2-hydroxy-2-phenyl-ethyl)-3-methyl-imidazolium
tri¯ate 425a-Otf) was obtained. The generation of 3-methyl-
imidazolium-N-di¯uoromethylides can also be easily
realized by reacting imidazolium-1-yl-di¯uoromethyltri-
methylsilane tri¯ates 413a,b) under ¯uoride catalysis. The
corresponding 2-phenyl-imidazolyl-1-di¯uoromethyl anion
was generated and its derivatives were produced under
the same conditions. Like heteroaryl-N-di¯uoromethyltri-
Fig. 1. Molecular structure of 12b 4thermal ellipsoids with 50%
probability). Selected bond lengths 4pm) and angles 48) Si41)±C42)
185.344), Si41)±C41) 193.844), F41)±C41) 138.344), F42)±C41) 137.544),
N41)±C47) 138.844), N41)±C45) 139.444), N41)±C41) 144.244), N42)±C47)
132.144), N42)±C46) 137.745), C43)±Si41)±C42) 112.242), C42)±Si41)±C41)
101.41417), C47)±N42)±C46) 106.343), F42)±C41)±F41) 104.943), F42)±
C41)±N41) 106.343), N41)±C41)±Si41) 121.342).
powder in a methanol/water mixture at room temperature
[34] 4Scheme 5).
methylsilanes,
1-trimethylsilyldi¯uoromethyl-3-methyl-
imidazolium tri¯ate 413a) and cyclohexanone in presence
of equimolar amounts of tetramethylammonium ¯uoride
reacted to give 1-41,1-di¯uoro-1-cyclohexanol-1-yl-
methyl)-3-methyl-imidazolium tri¯ate with 76% 486% 19F
NMR), 26a-OTf after hydrolysis. In the case of tetramethy-
lammonium ¯uoride catalysis only heteroarylium-N-di¯uor-
omethyl derivatives were observed 4Scheme 6).
2.5. Crystal structure of 2-phenyl-imidazole-1-yl-
difluoromethyltrimethylsilane 912b)
The molecular structure of imidazole 12b exhibited a
relatively long Si41)±C41) 4193.844) pm) bond 4see Fig. 1),
slightly longer than the comparable Si±C bond in bis4tri-
¯uoromethyl) trimethylsiliconate [35] or in tri¯uoromethyl-
triphenylsilane [36]. The angles and bond lengths in the
imidazole ring correspond to ``normal'' imidazole-rings
[37]. The CF2SiMe3 unit is essentially tetrahedral, whereas
the angle N41)±C41)±Si41) 121.342)8 is considerably larger
than expected.
3. Experimental
All reactions were performed under nitrogen in carefully
dried solvents. Mass spectra were recorded on a Finnigan
Scheme 6.

178
G. Bissky et al. / Journal of Fluorine Chemistry 109 92001) 173±181
MAT 8222 spectrometer under EI and FAB conditions, for
the covalent and ionic derivatives, respectively. NMR spec-
tra were recorded on a Bruker DPX-200 spectrometer
operating at 200.13 for 1H 4TMS), 188.31 for 19F 4CClF3),
50.32 MHz for 13C 4TMS), some 13C NMR spectra were
recorded on a Bruker AMX-360 spectrometer at 90.56 MHz
4TMS). Compounds 8a,b, 12a,b, 14a,b, 15b, 20, 26a-OTf
were prepared according to [26], for compound 11 see
also [24]. Cyclic voltammetry was performed using a
`home-made' potentiostat [38] with a positive feedback
Ohmic drop compensation and a Tacussel GSTP4 signal
generator. The working electrode was a glassy carbon
4Tokai Corporation) disc 43 mm diameter) and the reference
electrode a SCE. The supporting electrolyte was tetrabu-
tylammonium hexa¯uorophosphate 4NBu4PF6; Fluka pur-
iss). For puri®cation of solvents used for cyclic
voltammetry cf. [7,8].
JHH ˆ 8:3 Hz); 19F NMR d 4CD3CN† ˆ À80:4 4s, CF3),
À82.2 4d, CF2, 2JPF ˆ 70:7 Hz); 31P NMR
4CD3CN† ˆ 15:7 4t, 1P); HRMS calcd. for C20H20N2F2P
357.13322; found 357.132221.
d
‡
3.4. 1-9Difluoro-trimethylsilyl-methyl)-4-dimethylamino-
pyridinium triflate 94)
Yield 53%; mp 117±1188C; 1H NMR d 4CDCl3† ˆ 0:3 4s,
CH3), 3.3 4s, CH3), 7.2 4d, CH, JHH ˆ 7:8 Hz), 8.0 4d,
JHH ˆ 8:3 Hz), 19F NMR d 4CDCl3† ˆ À79:5 4s, CF3),
À92.9 4s, CF2); 13C NMR d 4CDCl3) À5.0 4CH3), 40.6
4CH3), 120.7 4q, CF3, JCF ˆ 321:0 Hz), 125.6 4t, CF2,
JCF ˆ 303:7 Hz), 108.6±157.3 4m); HRMS calcd. for
‡
C11H19N2F2Si 245.12856; found 245.12877; anal. calcd.
for C12H19N2F5SiO3S: C 36.54, H 4.86, F 24.08; found C
36.48, H 4.79, F 24.0%.
3.1. 1-91,1-Difluoro-2-hydroxy-2-phenyl-ethyl)-4-
dimethylamino-pyridinium bromide 92)
3.5. 1-91,1-Difluoro-2-hydroxy-2-phenyl-ethyl)-3-methyl-
imidazolium triflate 925a-OTf)
To a solution of 2.62 g 47.89 mmol) of 1 and 4.18 g
439.5mmol) of benzaldehyde in 15 ml benzonitrile was
added at À208C in 1.58 g 47.89 mmol) of TDAE, stirred
at À208C for 1 h and for 1 h at ambient temperature. After
®ltrating-off TDAE2‡ 2BrÀ, 20 ml water was added, then
the remaining water evaporated and the residue recrystal-
lized from acetonitrile. Yield of 2 1.3 g 446%), mp 2258C;
1H NMR 4CD3CN) d ˆ 3:3 4s, CH3), 4.7 4s, CH), 5.5 4s,
OH), 7.1 4s, CH), 7.4 4s, CH), 8.3 4s, CH); 19F NMR d
Yield 47%; mp 112±1138C; 1H NMR d 4CDCl3† ˆ 3:9 4s,
CH3), 4.7 4s, CH), 5.5 4s, OH), 7.6 4s, CH), 7.7 4s, CH), 9.2 4s,
CH); 19F NMR d 4CDCl3) À80.5 4s, CF3), À86.9 4dd, CF2,
3
JFF ˆ 209:8, JFH ˆ 3:5 Hz), À98.3 4dd, CF2, JFF 209.8,
3JFH 14.1 Hz); 13C NMR 4&) 4CDCl3† ˆ 39:3 4s, CH3),
2
72.5 4t, CH, JCF ˆ 31:9 Hz), 129.3 4t, JCF ˆ 275:3 Hz),
124.1 4s, CH), 121.9 4q, JCF ˆ 320:8 Hz), 129.5±141.9 4m);
‡
HRMS calcd. for C12H13N2F2O 239.22316; found:
239.22738.
3
4CD3CN† ˆ À91:9 4dd, JFF ˆ 202:7, JFH ˆ 3:6 Hz),
3
À101.3 4dd, JFF ˆ 202:7, JFH ˆ 3:6 Hz); 13C NMR d
3.6. 1-91,1-Difluoro-2-hydroxy-2-phenyl-ethyl)-2-phenyl-
3-methyl-imidazolium triflate 925b-OTf)
4CD3CN† ˆ 41:2 4s, CH3), 73.2 4m, CH), 121.0 4t, CF2,
JCF ˆ 270:5 Hz), 108.0±157.8 4m); HRMS calcd. for
‡
Yield 54%; mp 122±1238C; 1H NMR d 4CDCl3† ˆ 3:8 4s,
CH3), 4.5 4s, CH), 5.7 4s, OH), 7.2±7.7 4m, 7H); 19F NMR d
4CDCl3† ˆ À80:4 4s, CF3), À82.3 4dd, JFF ˆ 201:8, CF2,
C15H17N2F2O 279.13089; found 279.13250; anal. calcd.
for C15H17N2F2OBr: C 50.15, H 4.77, F 10.58; found: C
50.25, C 4.85, F 10.7%.
3JFH ˆ 3:4 Hz),
À92.8
4dd,
CF2,
JFF ˆ 219:3,
3JFH ˆ 13:1 Hz); 13C NMR 4&) 4CDCl3† ˆ 40:1 4s,
3.2. Typical procedure for 3, 4, 25a,b-OTf
CH3), 85.2 4t, CH, 2JCF ˆ 28:1 Hz), 135.2 4t,
1
To a solution of 2.74 g 425.3 mmol) of chlorotrimethyl-
silane and 0.84 g 42.53 mmol) of 1 in 15 ml benzonitrile
was added at À208C in 0.51 g 42.53 mmol) of TDAE,
stirred at À208C for 1 h and for 1 h at ambient tempera-
ture. After ®ltrating-off TDAE2‡ 2BrÀ, trimethylsilyl
tri¯ate 0.42 g 42.53 mmol) was added and the solution
stirred for additional 15 min at ambient temperature. After
evaporation of the solvent under reduced pressure, the
residue was recrystallized from THF. Yield of 4 0.53 g
453%).
1JCF ˆ 289:4 Hz), 121.8 4q, JCF ˆ 320:7 Hz), 124.5±
‡
145.1 4m); HRMS calcd. for C18H17N2F2O 315.31498;
found: 315.31453.
3.7. Tetramethylammonium 1-91,1-difluoro-2-phenyl-
ethylat)-4-dimethylamino-pyridinium triflate 95)
1
Yield 32%; mp 254±2568C; H NMR d 4CD3CN† ˆ 3:1
4s, CH3), 3.2 4s, CH3), 4.7 4s, CH), 7.2 4s, CH), 7.4 4s, CH),
8.3 4s, CH); 19F NMR d 4CD3CN† ˆ À80:4 4s, CF3), À93.8
4dd, JFF ˆ 200:1, 3JFH ˆ 3:0 Hz), À103.6 4dd, JFF ˆ 200:1,
3JFH ˆ 13:8 Hz); 13C NMR d 4CD3CN† ˆ 40:3 4s, CH3),
56.3 4s, CH3), 120.9 4q, CF3, JCF ˆ 321:1 Hz), 125.6 4t, CF2,
JCF ˆ 303:7 Hz), 107.4±159.1 4m); anal. calcd. for
C20H28F5N3O4S: C 47.90, H 5.63, F 18.94; found: C
47.85, H 5.69, F 19.01%.
3.3. 1-9Difluoro-diphenyl-phosphanyl-methyl)-4-
dimethylamino-pyridinium triflate 93)
1
Yield 67%; mp 115±1168C; H NMR d 4CD3CN† ˆ 3:2
4s, CH3), 6.8 4d, CH, JHH ˆ 8:3 Hz), 8.0 4d, CH,

G. Bissky et al. / Journal of Fluorine Chemistry 109 92001) 173±181
179
3.8. 1-Difluoromethyl-2-methyl-benzimidazole 911) [24]
Yield 70%; mp 34±378C; bp 68±708C/0.005 Torr; 1H
tri¯ate. The precipitate was ®ltrated-off and washed with
10 ml of pentane. Yield of 13b 1.53 g.
5
NMR d 4CDCl3† ˆ 2:7 4t, CH3, JFH ˆ 2:9 Hz), 7.3±7.7
3.13. 1-Trimethylsilyldifluoromethyl-3-methyl-
imidazolium triflate 913a)
4m, Ar); 19F NMR d 4CDCl3† ˆ À27:9 4s, CF2); 13C NMR d
4
4CDCl3† ˆ 16:6 4t, CH3, JCF ˆ 4:5 Hz), 109.2 4t, CF2Br,
JCF 307.4 Hz), 112.3 4t, C-CH3, JCF ˆ 5:3 Hz), 119.8±
Yield 100%; mp 62±638C; 1H NMR d 4CDCl3† ˆ 0:0 4s,
CH3), 3.6 4s, CH3), 7.1 4dd, 3JHH 2.3 Hz, 4JHH 0.8 Hz, CH),
7.1 4m, CH), 7.7 4s, CH); 19F NMR d 4CDCl3† ˆ À79:6
4CF3), À78.9 4CF2); 13C NMR d 4CDCl3† ˆ À3:4 4CH3),
39.0 4s, CH3), 121.6 4q, JCF ˆ 322:5 Hz), 121.5 4t,
3
149.3 4Ar, m); HRMS calcd. for C9H7N2F279Br
259.97607; found 259.97648.
3.9. Typical procedure for 12a,b [34], 17a, 20 [31]
‡
JCF ˆ 233:1 Hz); HRMS calcd. for C8H15N2F2Si :
To a solution of 0.59 g 43 mmol) of 8a and 3.6 g
433 mmol) of Me3SiCl in 9 ml CH2Cl2 was added dropwise
in 0.82 g 43.3 mmol) tris4diethylamido)phosphite at À708C.
After stirring for 1 h at this temperature, 0.5 h at ambient
temperature and pumping off of the solvent, the crude
product was extracted from the residue with 3Â5 ml pentane
and recrystallized from hexane. Yield of 12a 0.49 g 485%),
colorless oil.
205.26143; found: 205.26135.
3.14. 1-Trimethylsilyldifluoromethyl-2-phenyl-3-
methyl-imidazolium triflate 913b)
Yield 100%; mp 75±768C; 1H NMR d 4CDCl3† ˆ 0:1 4s,
CH3), 3.7 4s, CH3), 7.5±7.8 4m, 7H); 19F NMR d
4CDCl3† ˆ À79:6 4CF3), À82.8 4CF2); 13C NMR d
4CDCl3† ˆ À3:6 4CH3), 37.7 4s, CH3), 121.6 4q,
JCF ˆ 322:5 Hz), 123.1 4t, JCF ˆ 242:1 Hz), 119.7±145.3
3.10. Imidazol-1-yl-difluoromethyl-diphenyl-
phosphine 917a)
‡
4m); HRMS calcd. for C14H19N2F2Si : 281.12634; found:
281.12598.
Yield 78%; mp 80±828C; 1H NMR d 4CD3CN† ˆ 7:1 4dd,
3
4
CH, JHH ˆ 2:2, JHH ˆ 1:0 Hz), 7.3 4m, CH), 7.3±7.7 4m,
Ar) 7.9 4s, CH), 19F NMR d 4CD3CN† ˆ À72:9 4d, CF2,
2JPF ˆ 79:3 Hz); 31P NMR d 4CD3CN† ˆ À10:5 4t); HRMS
calcd. for C16H13N2F2P: 302.07844; found: 302.07867.
3.15. 1-Bromodifluoromethyl-3-methyl-imidazolium
triflate 924a-OTf)
Yield 100%; mp 49±518C; 1H NMR d 4CDCl3† ˆ 3:9 4s,
CH3), 7.6 4s, CH), 7.9 4s, CH), 9.3 4s, CH); 19F NMR d
4CDCl3† ˆ À34:5 4s, CF2), À80.6 4s, CF3); 13C NMR d
4CDCl3† ˆ 37:9 4CH3), 108.0 4t, CF2, JCF ˆ 309:8 Hz),
118.3 4CH), 121.9 4q, CF3, JCF ˆ 320:9 Hz), 126.8 4s,
3.11. 2-Phenyl-benzimidazole-1-yl-2,2-difluoro-
1-phenyl-ethanol 921) [24]
‡
To a solution of 4.0 g 415.7 mmol) of 20 and 8.32 g
478.5 mmol) of benzaldehyde in 20 ml monoglyme 0.04 g
tetramethylammonium ¯uoride [39] was added and the
mixture stirred for 20 h. The solvent and excess of benzal-
dehyde were evaporated and the residue was treated with
50 ml 10% hydrochloric acid. The precipitate was ®ltrated-
off and washed with a sodium hydrogencarbonate solution,
then extracted with hot chloroform. After evaporation of
chloroform the product was recrystallized from a hexane/
CH), 137.0 4s, CH); HRMS calcd. for C5H6N2F279Br
210.96824; found 210.97041.
3.16. 1-Bromodifluoromethyl-2-phenyl-3-methyl-
imidazolium triflate 924b-OTf)
1
Yield 100%; mp 64±658C; H NMR d 4CDCl3) 3.8 4s,
CH3), 7.3±8.0 4m, 7H); 19F NMR d 4CDCl3) À30.2
4s, CF2Br), 79.6 4s, CF3); 13C NMR d 4CDCl3) 36.8 4s,
CH3), 116.0 4q, JCF 321.0 Hz), 108.6 4t, JCF 308.3 Hz),
100.5±144.6 4m, Ar); anal. calcd. for C12H10N2O3F5SBr:
C 32.97, H 2.31, F 21.73; found C 32.72, H 2.42, F 21.5.
1
chloroform 41/1) mixture. Yield 3.7 g 481%); H NMR d
4CDCl3† ˆ 2:3 4t, CH3, 5JFH ˆ 2:9 Hz), 5.3 4dd, CH), 6.8 4d,
4
OH, JFH ˆ 5:4 Hz), 7.1±7.6 4m, Ar); 19F NMR d
4CDCl3† ˆ À86:5 4d, CF2, JFF ˆ 217:3 Hz), À92.1 4dd,
3
1JFF ˆ 217:2, JFH ˆ 12:1 Hz); 13C NMR d 4CDCl3† ˆ
3.17. 1-Trifluoromethyl-imidazole 918a)
4
16:8 4t, CH3, JCF ˆ 4:5 Hz), 73.8, 74.1 4AB system, CH,
3
To a solution of 1.37 g 47.65 mmol) of antimony tri¯uor-
ide was added 1.5 g 476.5 mmol) 8a. The mixture was
heatedat 608C for 24 h and the product extracted with hot
hexane. After evaporating hexane 0.31 g 430%), bp 63±
JAB ˆ 30:9 Hz), 113.3 4t, JCF ˆ 5:3 Hz), 121.2 4t, CF2,
1JCF ˆ 262:2 Hz), 119.6±151.6 4m, Ar); HRMS calcd. for
C16H14ON2F2: 288.10792; found: 288.10742.
3
3.12. Typical procedure for 13a,b, 24a,b-OTf
648C; 1H NMR d 4CDCl3† ˆ 7:2 4dd, CH, JHH ˆ 2:2,
4JHH ˆ 1:0 Hz), 7.3 4m, CH), 7.9 4s, CH), 19F NMR d
4CDCl3† ˆ À58:5 4CF3); 13C NMR d 4CDCl3† ˆ 115:3
4q, CF3, JCF ˆ 319:4 Hz), 116.0 4s, CH), 130.9 4s, CH),
To a solution of 0.95 g 43.57 mmol) of 12b in 5 ml
pentane was added dropwise in 0.61 g 43.75 mmol) methyl

180
G. Bissky et al. / Journal of Fluorine Chemistry 109 92001) 173±181
133.9 4s, CH); HRMS calcd. for C4H3N2F3 136.07612;
found 136.07635.
4. Conclusions
A convenient synthesis of new N-CF2Br heterocyclic
compounds 4and their N-CF3 derivatives) has been found
and their chemical and electrochemical reactivity studied.
1,3-Dipolar cycloaddition reactions of 4-dimethylaminopyr-
idinium-1-di¯uoromethylide and 3-methyl-imidazolium-1-
di¯uoromethylide with electron de®cient 4¯uorinated)
alkenes and alkynes and other examples of anionic hetero-
aryl-N-di¯uoromethylation reactions with heteroaryl-N-
di¯uoromethyltrimethylsilanes will be published in due
course. Similarly the generation of the N±CF2 radicals
and their synthetic reactions will be studied.
3.18. Typical procedure for 19a,b, 22
In a 10 ml methanol/water 41/1) mixture to 0.7 g
43.6 mmol) 8a were added 0.6 g 49.2 mmol) zinc and stirred
for 24 h. The mixture was re¯uxed and extracted with
5Â10 ml hot hexane. Recrystallization from hexane gave
0.4 g 19a 495%).
3.19. 1-Difluoromethyl-imidazole 919a)
At bp 156±1578C 4155±1568C) [23]; 19F NMR d 4CDCl3)
2
À93.0 4d, JFH ˆ 60:4 Hz).
Acknowledgements
3.20. 1-Difluoromethyl-2-phenyl-imidazole 919b)
Financial support by the Deutsche Forschungsge-
meinschaft 4A.K.), CNRS 4M.M.), Royal Society of Chem-
istry Journals' Grants for International Authors 4A.K.) are
gratefully acknowledged. Dr. S. Pazenok 4former Hoechst
AG) is thanked for helpful discussions.
Yield 95%; mp 67±688C 461±628C) [23]; 19F NMR d
4CDCl3† ˆ À92:0 4d, JFH ˆ 60:4 Hz).
2
3.21. 1-Difluoromethyl-2-methyl-benzimidazole 922)
Yield 95%; bp 738C/0.01 Torr 41028C/1.4 Torr) [24]; 19
NMR d 4CDCl3† ˆ À96:1 42JFH ˆ 58:6 Hz).
F
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