A new synthesis of N-substituted -trifluoroacetylanilines

Article abstract of DOI:10.1016/j.jfluchem.2012.07.002

A method for the synthesis of N-substituted -trifluoroacetylanilines by the reaction of N-substituted isatoic anhydrides with (trifluoromethyl) trimethylsilane (Ruppert-Prakash reagent) has been developed. This method provides easy access to both N-alkyl - trifluoroacetylanilines and N-aryl - trifluoroacetylanilines in high yields. Cyclisation of N-aryl - trifluoroacetylanilines in trifluoroacetic acid gives 9- trifluoromethylacridines.

Full text of DOI:10.1016/j.jfluchem.2012.07.002

Journal of Fluorine Chemistry 143 (2012) 272–280
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
A new synthesis of N-substituted @-trifluoroacetylanilines
*
Alexander F. Shidlovskii, Alexander S. Golubev , Dmitrii V. Gusev, Kyrill Yu. Suponitsky,
Alexander S. Peregudov, Nikolai D. Chkanikov
A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov St. 28, GSP-1, Moscow, Russian Federation
A R T I C L E I N F O
A B S T R A C T
Article history:
A method for the synthesis of N-substituted @-trifluoroacetylanilines by the reaction of N-substituted
isatoic anhydrides with (trifluoromethyl)trimethylsilane (Ruppert–Prakash reagent) has been devel-
oped. This method provides easy access to both N-alkyl-@-trifluoroacetylanilines and N-aryl-@-
trifluoroacetylanilines in high yields. Cyclisation of N-aryl-@-trifluoroacetylanilines in trifluoroacetic
acid gives 9-trifluoromethylacridines.
Received 20 April 2012
Received in revised form 30 June 2012
Accepted 5 July 2012
Available online 16 July 2012
ß 2012 Elsevier B.V. All rights reserved.
Keywords:
N-substituted isatoic anhydrides
Ruppert–Prakash reagent
N-substituted @-trifluoroacetylanilines
9-Trifluoromethylacridines
1. Introduction
lithiated N-Piv(N-Boc)-anilines, strong bases such as n-BuLi or
tert-BuLi are used for obtaining dilithio intermediates in the first
@-Trifluoroacetylanilines are widely used for the synthesis of
physiologically active heterocycles including HIV-1 reverse
transcriptase inhibitors [1], antidiabetic drugs [2], fluorinated
analogues of cytotoxic alkaloid luotonine [3], homocamptothecin
[4], selective androgen receptor modulator [5], and G-type calcium
channel antagonists [6]. @-Trifluoroacetylanilines exhibit antiher-
petic activity [7], they are extensively studied as molecular sensors
[8].
stage of the synthesis [9]. As a result, the lithiation reaction of N-Piv-
toluidine leads to lateral rather than nuclear lithiation [13]. For 3,4-
dichloroaniline, the yield of the target 1-(2-amino-5,6-dichloro-
phenyl)-2,2,2-trifluoroethanoneisrather low(19%) becauseofa side
reaction of HCl elimination. The same limitation operates when
other 3-chloroanilines are applied [9c]. @-Trifluoroacetylanilines
with a nitro group are not available by aniline lithiation approach.
They can be obtained by a tedious multistep synthesis, which
Several approaches towards the synthesis of @-trifluoroacety-
lanilines exist. @-Trifluoroacetylation of lithiated anilines bearing
a N-protecting and ortho-directing group (usually Piv- or Boc-
group) [9], nucleophilic substitution by N-nucleophiles of fluorine
includes a Weinreb amide reduction step [14]. Most 2-fluoro-a,a,a-
trifluoroacetophenones used for the synthesis of @-trifluoroacety-
lanilines were obtained by lithiation (in this case with LDA) of the
corresponding fluorobenzenes [10]. The reaction operates at
cryogenic temperatures and suffers often from lack of regioselec-
tivity [15]. Nucleophilic substitution by N-nucleophiles of dimethy-
lamino group in N,N-dimethyl-2-trifluoroacetyl-naphthylamines is
restricted to the naphthalene nucleus, as N,N-dimethyl-2,4-bis(tri-
fluoroacetyl)aniline does not react [11]. Insertion of arynes proceeds
in the E–N bond of N-aryltrifluoroacetamides. No examples were
given for obtaining of N-alkyl @-trifluoroacetylanilines by this
method [12].
in 2-fluoro-a,a,a-trifluoroacetophenones [10] and dimethyla-
mino group in N,N-dimethyl-2-trifluoroacetyl-naphthylamines
or N,N-dimethyl-5,7-bis(trifluoroacetyl)-8-quinolylamines [11],
and insertion of arynes in the E–N bond of N-aryltrifluoroace-
tamides to give N-aryl-@-trifluoroacetylanilines [12] can be
considered as most important methods for the synthesis of
@-trifluoroacetylanilines.
The above mentioned approaches make it possible to synthesize
@-trifluoroacetylanilines containing various substituents in the
aromatic ring, as well as their N-substituted analogues. However
all these methods have their own limitations. In particular, in the
synthesis of @-trifluoroacetylanilines by trifluoroacetylation of
Moreover, a general method for synthesizing N-substituted @-
trifluoroacetylanilines does not exist.
2. Results and discussion
Our approach to the synthesis of N-substituted @-trifluoroace-
tylanilines is based on the reaction of isatoic anhydride derivatives
(2H-3,1-benzoxazine-2,4(1H)-diones 1) with Ruppert–Prakash
* Corresponding author. Tel.: +7 499 135 9358; fax: +7 499 135 0176.
E-mail address: golubev@ineos.ac.ru (A.S. Golubev).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.07.002

A.F. Shidlovskii et al. / Journal of Fluorine Chemistry 143 (2012) 272–280
273
O
O
F3C
OSiMe3
O
CF3SiMe3
CF3
4
O
2
NH
R
N
R
O
N
R
O
2
A
1
Scheme 1.
reagent (CF3SiMe3 [16]) (Scheme 1). We envisioned that a
nucleophilic attack of Ruppert–Prakash reagent would occur
predominantly at position 4 of heterocycle 1, rather than at
position 2 to provide high regioselectivity of the process as a result.
We also assumed that intermediate compound ! should be
sufficiently stable under the reaction conditions to hinder the
second attack of Ruppert–Prakash reagent with formation of
bis(trifluoromethyl)carbinols as a by-product.
When our research in this direction had been almost completed,
Braese and co-workers published a paper [17] where their attempt
to realize a similar synthetic idea was described. They studied
reaction of 2-methyl-(4H)3,1-benzoxazin-4-one with Ruppert–
Prakash reagent in various solvents in the presence of tetra-
butylammonium fluoride (GB!F) as catalyst. Dimethylsulfoxide
proved to be the solvent of choice. The yields of @-trifluoroace-
tylanilines were low (13–53%) even when applying a 3-fold excess
of Ruppert–Prakash reagent [17].
In this paper we show our results on the synthesis of various N-
substituted @-trifluoroacetylanilines by the reaction of Ruppert–
Prakash reagent with N-substituted 2H-3,1-benzoxazine-
2,4(1H)-diones 1. After initial experiments, we selected DMF as
the solvent of choice, because the transfer of the CF3 group in DMF
is rather fast, and the treatment of the reaction mixture is very
simple. We used a combination of KF and tetrabutylammonium
bromide (GBAB) as catalyst. This combination is rather cheap, and
provides reliable catalysis for CF3-group transfer, and it does not
bring water into the reaction mixture. Tetrabutylammonium
fluoride (TBAF), which is usually used for such reactions, should be
additionally dried, because otherwise the water it contains
hydrolyses the starting reactants under the reaction conditions.
In all reactions studied, we used a 30% excess of Ruppert–Prakash
reagent to achieve the full conversion of starting benzoxazin-2,4-
diones 1.
We have discovered that N-alkylisatoic anhydrides 1a–d
reacted with Ruppert–Prakash reagent in DMF in the presence
of KF + GBAB at room temperature to give N-substituted @-
trifluoroacetylanilines 2a–d in high yields (85–90%, Table 1).
The reaction was monitored by 19F NMR spectroscopy. As
reaction occured, the intensity of the signal at À65.1 ppm
(CF3SiMe3) decreased while the signal at about À85.0 ppm
(assigned to compound A, Scheme 1) increased. Conversion of
benzoxazin-2,4-diones 1a–d was estimated by TLC. The reaction
was treated with a 5% solution of HCl to remove the trimethylsilyl
moiety in ketal A, then with a 10% solution of sodium carbonate to
decompose desilylated ketal A, which is quite stable in solutions of
mineral acids [18].
We failed to avoid the formation of by-product 3a at all by
either decreasing the excess of Ruppert–Prakash reagent or
varying the solvent. The commercial TBAF led to somewhat worse
results in comparison with the combination KF + TBAB, and the
presence of NaOAc resulted in formation of several by-products.
The use of THF decreased the yield of product 2a as a result of
incomplete conversion even upon prolonged (for 24 h) stirring. The
low yield of product 2a was observed in methylene chloride
because of low conversion of starting 1a.
We failed to isolate N-cyanomethylated @-trifluoroacetylaniline
from the reaction of N-cyanomethylisatoic anhydride with
Ruppert–Prakash reagent. Probably, an enhanced acidity of the
cyanomethyl fragment prevents KF + TBAB (and also TBAF) from
catalysis of CF3-group addition reaction. Isatoic anhydride itself did
not react with Ruppert–Prakash reagent under the aforesaid
conditions.
We extended a set of the N-alkylsubstituted @-trifluoroace-
tylanilines obtained by modifying the aromatic ring. For
instance, N-methyl-4-bromo-2-trifluoroacetylaniline 2b gave
4-phenyl derivatives 2e in 95% yield. Therefore the N-alkyla-
mino- and o-trifluoroacetyl groups do not hinder the Suzuki
reaction (Scheme 3).
We have also found that N-arylisatoic anhydrides 4a–d reacted
with Ruppert–Prakash reagent in DMF in the presence of KF + GBAB
at room temperature to give N-arylated @-trifluoroacetylanilines
5a–d in good to high yields (Table 2).
In contrast to N-alkylisatoic anhydrides 1a–d, reaction of N-
phenylisatoic anhydride 4a with Ruppert–Prakash reagent
proceeded much more slowly. It took usually about 16 h to
reach a high conversion of 4a at 25 8C. Moreover, we observed
clear evidences of instability of the initial cyclic ketal A (Scheme
1, R = Ph) in DMF. Monitoring the reaction by 19F NMR
spectroscopy detected along with the signal at À65.1 ppm
(CF3SiMe3) and the signal at about À85.0 ppm (assigned to
cyclic ketal A, Scheme 1), three other intensive signals, a singlet
at À67.8 ppm (ketone 5a), a singlet at À72.81 ppm, and a broad
singlet at À66.17 ppm. While reaction is proceeding, the
intensity of the signal at À85.0 ppm decreases, a singlet at
À67.8 ppm (ketone 5a) increases, and arises a new signal – a
singlet at À71.25 ppm. After CF3SiMe3 was consumed and the
reaction was treated by diluted HCl (an additional treatment
with Na2CO3 was excessive in this case), all 4 initial signals
collapsed to a singlet at À67.87 ppm (ketone 5a). And only the
singlet at À71.25 ppm went unchanged after acidic treatment of
the reaction and clearly indicated presence of a by-product in
this reaction in notable amounts (up to 8%). We isolated this by-
product. Its structure as bridged diazocine 6a was confirmed by
X-ray diffraction method (Fig. 1) [19]. We found that the content
of the by-product 6a in the reaction mixture was increased to
20–25% when running the reaction at 35 8C.
In all cases, the content of by-products in the reaction mixture
did not exceed 5% (according to 19F NMR data). By the example of
reaction of benzoxazine-2,4-dione 1a, we found out formation of
bis(trifluoromethyl)carbinol 3a to account for side reaction to a
great extend. Carbinol 3a was isolated from the reaction mixture
and characterized. Its structure was also confirmed independently
by the reaction of Ruppert–Prakash reagent with o-aminoketone
2a (Scheme 2).
All these observations testify to the fact that instability of the
initial cyclic ketal A in DMF and the formation of by-product 6a are
intrinsically connected. To mention, on monitoring the reaction of
benzoxazin-2,4-diones 1a–d with CF3SiMe3 to give quite stable

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A.F. Shidlovskii et al. / Journal of Fluorine Chemistry 143 (2012) 272–280
Table 1
Reaction conditions and yields for the reaction of N-alkylbenzoxazin-2,4-diones 1a–d with Ruppert’s reagent.
2H-3,1-benzoxazin-2,4(1H)-dione
Solvent
DMF
Eatalyst
Product
Isolated yield, %
87b
KF + TBABa
O
O
O
CF3
N
O
NH
CH3
CH3
1a
1a
2a
2a
DMF
DMF
THF
TBAF
73
1a
1a
1a
NaOAc
2a
65c
61d
40c,e
80
TBAF
2a
CH2Cl2
DMF
KF + TBABa
KF + TBABa
2a
O
N
O
Br
Br
O
CF3
O
NH
CH3
CH3
2b
1b
O
DMF
DMF
KF + TBABa
85
90
O
CF3
O
NH
N
O
CH2Ph
CH2Ph
1c
2c
KF + TBABa
O
O
O
N
CF3
O
NH
CH2CH=CH2
CH2CH=CH2
1d
2d
DMF
KF + TBABa or TBAF
traces of product
–
O
O
N
O
CN
Isatoic anhydride
DMF
KF + TBABa
no reaction
–
a
30 mol% referred to a N-alkylbenzoxazin-2,4-dione, in a ratio 1:1.
Compound 3a (2%) was also isolated.
b
c
In addition to by-products (according to 19F NMR spectral data).
Incomplete conversion for 24 h.
d
e
Incomplete conversion for 164h.
O
O
O
F3C
CF3
OH
Br
Ph
CF3
PhB(OH)2
CF3
CF3SiMe3, cat
CF3
NH
Pd(OAc)2, Cy3P
NH
DMF, 20 oC
NH
NH
CH3
CH3
CH3
CH3
2b
2a
3a
2e
Scheme 2.
Scheme 3.

A.F. Shidlovskii et al. / Journal of Fluorine Chemistry 143 (2012) 272–280
275
cyclic ketals A (R = alkyl, Scheme 1), no analogous to 6a by-
products were detected. A plausible mechanism for the formation
of 6a is shown in Scheme 4.
N-phenylisatoic anhydride was identified as carbonyl dipolar-
ophile [20]. Apparently spectroscopically observed instable in
5a did not react with N-phenylisatoic anhydride in DMF in
presence of KF + TBAB even at 75 8C. It means that the formation of
6a by a reaction sequence including a nucleophilic attack of the
nitrogen atom of N-phenyl-o-trifluoroacetylaniline 5a on the C-4
atom of N-phenylisatoic anhydride followed by intramolecular
cyclisation with formation of diazocine ring can be excluded.
Further investigations to provide support to our interpretation
and to make use of this unusual reaction for diazocine synthesis
are under way.
DMF cyclic ketal
A decarboxylates to provide a putative
intermediate, which can act as 1,4-dipole [21]. 1,4-Cycloadduct
decarboxylates again to afford via a cascade process the formal
[4 + 4] dimer 6a. We found that N-phenyl-o-trifluoroacetylaniline
Table 2
Reaction conditions and yields for the reaction of N-arylbenzoxazin-2,4-diones 4a–d with Ruppert‘s reagent.
2H-3,1-benzoxazin-2,4(1H)-dione
Solvent
DMF
Catalyst
Product
Isolated yield, %
74b
KF + TBABa
O
O
CF3
O
NH
N
O
5a
4a
4b
DMF
KF + TBABa
83
O
O
O
CF3
N
O
NH
5b
O
O
O
DMF
KF + TBABa
67
O
O
CF3
N
O
NH
4c
5c
F
F
O
DMF
KF + TBABa
77 (5d)
5% (7d)c
O
F3C
CF3
OH
O
CF3
N
O
NH
NH
+
4d
CHPh2
5d
CHPh2
7d
CHPh2
a
30 mol % referred to a N-arylbenzoxazin-2,4-dione, in a ratio 1:1.
Compound 6a (6%) was isolated.
b
c
Compound 8d (5%) was also isolated.

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A.F. Shidlovskii et al. / Journal of Fluorine Chemistry 143 (2012) 272–280
O
F3C OSiMe3
CF3
F3C
O+
CF3SiMe3
OSiMe3
O
O
SiMe3
N
-CO2
KF+TBAB
DMF
N
O
N
O
N
Ph
O
Ph
Ph
Ph
O
A
N
O
Ph
CF3
OSiMe3
Ph
Ph
Ph
N
N
N
N
Ph
+
O
O
O
N
OSiMe3
CF3
+
O
+
O
OSiMe3
Me3SiO
CF3
Ph
CF3
-CO2
O
N
N
N
O
O
Ph
Ph
Ph
F3C
Ph
Ph
N
O
N
O
SiMe3
6a
Scheme 4.
Reaction of N-arylisatoic anhydrides 4b–d with Ruppert–
of N-(p-fluorophenyl)isatoic anhydride, but it was not isolated. In
the case of oxazin-2,4-dione 4d, we isolated another minor
component – bis(trifluoromethyl)carbinol 7d from the reaction
mixture (about 5%).
Prakash reagent proceeded faster than with N-phenylisatoic
anhydride 4a. The highest yield was obtained for anhydride 4b
(Table 2). Analogous to 6a by-product was detected in the reaction
We also observed the formation of
a minor fluorinated
component of another type in the reaction of benzoxazine-2,4-
diones 4a–d with Ruppert–Prakash reagent. A by-product of this
type gave a singlet (at about
d
À49 ppm) in the 19F NMR spectrum,
its content was up to 5%. In the case of benzoxazin-2,4-dione 4d,
we isolated this minor component and characterized it as 9-
trifluoromethylacridine 8d.
9-Trifluoromethylacridines as representatives of important
class of acridines [22] are of undoubted practical interest. To
our surprise, there is no any method for the synthesis of 9-
trifluoromethylacridines in literature [23]. We have found that N-
arylsubstituted @-trifluoroacetylanilines 5a–d underwent intra-
molecular cyclisation to give 9-trifluoromethylacridines 8a–d in
50–70% yield upon prolonged (for 3–7 days) stirring in trifluor-
oacetic acid [23a] (Scheme 5).
O
CF3
CF3CO2H
CF3
R
NH
N
8a-d
5a-d
R = H, MeO, F, CHPh2
R
Fig. 1. ORTEP view (drawn at 30% probability of thermal displacement ellipsoids) of
6a.
Scheme 5.

A.F. Shidlovskii et al. / Journal of Fluorine Chemistry 143 (2012) 272–280
277
3. Conclusion
110.5, 29.5 (NHMe).19F NMR (282.38 MHz, CDCl3):
d
À67.69 (d,
5JH,F = 2.5 Hz, 3F, CF3). EIMS 70 eV, m/z: 204 [M+H]+ (33), 203 [M]+
(32), 134 [MÀCF3]+ (100), 106 [MÀCF3ÀCO]+ (28). Anal. Calcd for
C9H8F3NO: C, 53.21; H 3.97. Found C, 52.95; H, 4.22.
Therefore, we have developed a general and efficient method
for the synthesis of N-substituted @-trifluoroacetylanilines by the
reaction of N-substituted isatoic anhydrides with Ruppert–Prakash
reagent. This method provides easy access to both N-alkyl-@-
trifluoroacetylanilines and N-aryl-@-trifluoroacetylanilines in high
yields. Various N-alkyl- and N-arylisatoic anhydrides are commer-
cially available or can be easily prepared [24]. This makes it
The aqueous layer from the above reaction was extracted with
EtOAc (15 ml  3), dried over anhydrous MgSO4, and concentrated
under reduced pressure. The residue was purified by preparative
TLC on silica gel (toluene/hexanes/EtOAc = 2:1:1) to give
1,1,1,3,3,3-hexafluoro-2-[2-(methylamino)phenyl]propan-2-ol
(3a) (42 mg, 0.15 mmol, yield 2%) as a yellowish powder. Mp 80–
81 8C. 1H NMR (300.13 MHz, Me2SO-d6):
d 9.82 (1H, br s, NHMe),
7.29 (2H, m, Ar), 6.78 (1H, d, J = 8.8 Hz, Ar), 6.72 (1H, m, Ar), 6.15
(1H, br s, OH), 2.79 (3H, d, J = 4.2 Hz, NHMe). 13C (150.93 MHz,
possible to synthesize
a wide variety of N-substituted @-
trifluoroacetylanilines using the developed method. A method
for the synthesis of 9-trifluoromethylacridines has been developed
using the intramolecular cyclisation of N-aryl-@-trifluoroacetyla-
nilines in trifluoroacetic acid.
3
CDCl3):
d
147.3, 130.8, 128.7 m, JC,F = 3 Hz, CC(OH)(CF3)2, 125.8,
125.5, 123.4, 123.3 (q, 1JC,F = 291 Hz, CF3), 80.3 (sept, 2JC,F = 30 Hz,
C(CF3)2), 36.2 (NHMe).19F NMR (282.38 MHz, CDCl3):
4. Experimental
d
À74.43 (s,
6F, (CF3)2). EIMS 70 eV, m/z: 274 [M+H]+ (12), 273 [M]+ (58), 204
[MÀCF3]+ (100), 186 [MÀCF3ÀH2O]+ (52), 166 [MÀCF3ÀH2OÀHF]+
(90). Anal. Calcd for C10H9F9NO: C, 43.97; H 3.32; N 5.13. Found C,
43.62; H, 3.08; N, 4.88.
4.1. General
1H and 13C{1H} NMR spectra were recorded on a Bruker
AvanceTM 300 spectrometer (300.13 MHz and 75.46 MHz,
respectively), and on
a
Bruker AvanceTM 600 spectrometer
4.2.2. 2,2,2-Trifluoro 1-[5-bromo-2-(methylamino)phenyl]ethanone
(2b)
(600.21 MHz and 150.93 MHz, respectively). Chemical shifts for
protons and 13C nuclei were determined with respect to the
residual signal for chloroform (7.27 ppm) or the signal for CDCl3
(77.0 ppm), respectively and recalculated from the SiMe4 signal.
Chemical shifts were determined with accuracy no less than
0.001 ppm and 0.03 ppm, respectively. 19F NMR spectra were
recorded on a Bruker AvanceTM 300 spectrometer (282.38 MHz).
Chemical shifts for 19F nuclei were determined with respect to
trifluoroacetic acid as an external standard with accuracy no less
than 0.01 ppm and recalculated relative to CFCl3.
Mass spectra were obtained on a Finnigan Polaris Q instrument
(ion trap, 70 eV, the DIP procedure was used for the sample
injection). Silica gel with the particle size of 0.06—0.20 mm (Merck
Kieselgel 60) was used for column chromatography. Monitoring
the reaction course and purity of products obtained was performed
using Merck Kieselgel 60 F254 TLC plates. N,N-dimethylformamide
(99.8%, Panreac) was used as received.
Yellow powder. Yield 80%. Mp 101–102 8C. 1H NMR (300.13
MHz, CDCl3):
d 8.79 (1H, br s, NHMe), 7.91 (1H, pent, J = 2.0 Hz, Ar),
7.60 (1H, dd, J1 = 9.3 Hz, J2 = 2.0 Hz, Ar), 6.76 (1H, d, J = 9.3 Hz, Ar),
3.05 (3H, d, J = 5.3 Hz, NHMe). 13C (100.61 MHz, CDCl3):
d 179.4 (q,
2JC,F = 33 Hz, C(O)CF3), 152.9, 139.7, 133.5 (q, JC,F = 4 Hz,
3
1
CC(O)CF3), 116.7 (q, JC,F = 291 Hz, CF3), 113.7, 111.7, 105.9, 29.4
(NHMe).19F NMR (282.38 MHz, CDCl3):
d
À67.87 (d, JH,F = 2.0 Hz,
5
3F, CF3). EIMS 70 eV, m/z: 284 [M+H]+ (7), 283 [M+]+ (28), 282
[M+H]+ (10), 281 [M+]+ (31), 279 [M]+ (52), 215 [M+HÀCF3]+ (9),
214 [MÀCF3]+ (70), 213 [M+HÀCF3]+ (8), 212 [MÀCF3]+ (77), 134
[M+HÀCF3ÀBr]+ (14), 133 [MÀCF3ÀBr]+ (100). Anal. Calcd for
C9H7BrF3NO: C, 38.33; H 2.50; N 4.97. Found C, 38.55; H, 2.80; N,
4.62.
4.2.3. 2,2,2-Trifluoro-1-[2-(benzylamino)phenyl]ethanone (2c)
Yellow powder. Yield 85%. Mp 51–52 8C. 1H NMR (300.13 MHz,
Compounds 1a–1d and 4a–d were synthesized according to the
literature [24].
CDCl3):
d 9.20 (1H, br s, NHCH2), 7.87 (1H, m, Ar), 7.42 (6H, m, Ar),
6.82 (1H, d, J = 8.6 Hz, Ar), 6.74 (1H, dd, J1 = 8.1 Hz, J2 = 7.3 Hz, Ar),
4.59 (3H, d, J = 5.5 Hz, NHCH2). 13C (150.93 MHz, CDCl3):
d 180.7 (q,
3
4.2. General procedure for the synthesis of compounds 2a–d
2JC,F = 33 Hz, C(O)CF3), 153.3, 137.5, 137.3, 132.2 (q, JC,F = 4 Hz,
CC(O)CF3), 128.89, 127.8, 127.1, 117.3 (q, 1JC,F = 291 Hz, CF3), 115.4,
To a solution of the corresponding 1-alkyl-2H-3,1-benzoxazine-
2,4(1H)-dione (N-alkylisatoic anhydride) 1a–d (10 mmol), KF
(174 mg, 3 mmol) and TBAB (967 mg, 3 mmol) in dry DMF
(20 ml) was added trimethyl(trifluoromethyl)silane (1.85 g,
13 mmol) dropwise at 0 8C under argon. After completion of
addition, the reaction mixture was allowed to warm to rt and
stirred for 5 h. The reaction was quenched with 5% aq HCl solution
(10 ml) at 0 8C, allowed to warm to rt, and stirred for 0.5 h. To the
reaction mixture was added 10% aq Na2CO3 solution (50 ml) with
vigorous stirring, and stirring was continued for 1 h at rt. The
resulting emulsion was extracted with hexanes (60 ml  3). The
organic layer was separated, washed with brine (30 ml  2), dried
over anhydrous MgSO4, and concentrated under reduced pressure.
112.8, 110.8, 47.0 (NHCH2).19F NMR (282.38 MHz, CDCl3):
d
À76.53
(br. s, 3F, CF3). EIMS 70 eV, m/z: 280 [M+H]+ (13), 279 [M]+ (52), 210
[MÀCF3]+ (100), 208 [MÀCF3À2H]+ (32), 132 [MÀCF3ÀPh]+ (83).
Anal. Calcd for C15H12F3NO: C, 64.51; H 4.33; N 5.02. Found C,
64.33; H, 4.37; N, 5.12.
4.2.4. 2,2,2-Trifluoro-1-[2-(allylamino)phenyl]ethanone (2d)
Isolated by column chromatography on silica gel (chloroform/
hexanes = 1:3). Yellow oil. Yield 90%. 1H NMR (400.13 MHz, CDCl3):
d
8.74 (1H, br s, NHCH2CH=CH2), 7.83 (1H, m, J1 = 7.8 Hz,
J2 = 1.5 Hz, Ar), 7.47 (1H, ddd, J1 = 8.8 Hz, J2 = 7.6 Hz, J3 = 1.5 Hz,
Ar), 6.80 (1H, br. d, J = 8.8 Hz, Ar), 6.69 (1H, ddd, J1 = 7.8 Hz,
J2 = 7.6 Hz, J2 = 1.0 Hz, Ar), 5.98 (1H, m, CH=CH2), 5.32 (2H, m,
CH=CH2), 3.98 (2H, m, NHCH2CH=CH2). 13C (100.61 MHz, CDCl3):
d
2
4.2.1. 2,2,2-Trifluoro-1-[2-(methylamino)phenyl]ethanone (2a)
180.4 (q, JC,F = 33 Hz, C(O)CF3), 153.2, 137.0, 133.0, 131.9 (q,
Yellow oil. Yield 87%. 1H NMR (300.13 MHz, CDCl3):
d
8.79 (1H,
3JC,F = 5 Hz, CC(O)CF3), 117.1 (q, JC,F = 291 Hz, CF3), 116.6, 114.9,
1
5
br. s, NHMe), 7.84 (1H, dqd, J1 = 7.8 Hz, JH,F = 2.5 Hz, J2 = 1.4 Hz,
Ar), 7.55 (1H, ddd, J1 = 8.8 Hz, J2 = 7.3 Hz, J3 = 1.4 Hz, Ar), 6.84 (1H,
br. d, J = 8.8 Hz, Ar), 6.71 (1H, ddd, J1 = 7.8 Hz, J2 = 7.3 Hz,
112.5, 110.6, 44.9 (s, NHCH2CH=CH2).19F NMR: (282.38 MHz,
CDCl3)
d
À67.71 (br. s, 3F, CF3). EIMS 70 eV, m/z: 230 [M+H]+ (11),
229 [M]+ (33), 160 [MÀCF3]+ (58), 132 [MÀCF3ÀCO]+ (100), 130
[MÀCF3ÀCOÀ2H]+ (30), 117 [MÀCF3ÀCOÀCH3]+ (30). Anal. Calcd
for C11H10F3NO: C, 57.64; H 4.40; N 6.11. Found C, 57.95; H, 4.67;
N, 6.32.
J2 = 1.4 Hz, Ar), 3.05 (3H, d, J = 5.0 Hz, NHMe). 13C (150.93 MHz,
2
CDCl3):
d
180.4 (q, JC,F = 33 Hz, C(O)CF3), 154.4, 137.3, 132.1 (q,
3JC,F = 4 Hz, CC(O)CF3), 117.3 (q, JC,F = 291 Hz, CF3), 114.8, 111.9,
1

278
A.F. Shidlovskii et al. / Journal of Fluorine Chemistry 143 (2012) 272–280
4.2.5. Synthesis of 2,2,2-trifluoro-1-[2-
was added trimethyl(trifluoromethyl)silane (1.85 g, 13 mmol)
dropwise at 0 8C under argon. After completion of addition, the
reaction mixture was allowed to warm to rt and stirred for 16 h.
The reaction was quenched with 5% aq HCl solution (10 ml) at 0 8C,
allowed to warm to rt, and stirred 0.5 h.
(methylamino)phenyl]ethanone (2a) by the reaction in THF
To a solution of 1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione
1a (0.61 g, 3.45 mmol) and trimethyl(trifluoromethyl)silane
(638 mg, 4.49 mmol) in dry THF (15 ml) was added TBAF (1M in
THF; 0.52 ml, 0.52 mmol) dropwise at 0 8C under argon. After
completion of addition, the reaction mixture was allowed to warm
to rt and stirred for 24 h. The reaction was quenched with 5% aq HCl
solution (10 ml) at 0 8C, allowed to warm to rt, and stirred 0.5 h.To
the reaction mixture was added 10% aq Na2CO3 solution (50 ml)
under vigorous stirring, and stirring was continued for 1 h at rt. The
resulting solution was extracted with hexanes (60 ml  3). The
organic layer was washed with brine (30 ml  2), dried over
anhydrous MgSO4, and concentrated under reduced pressure to
afford ethanone 2a (0.43 g, 61% yield) as a yellow oil.
4.5.1. 2,2,2-Trifluoro-1-(2-anilinophenyl)ethanone (5a)
The isolation proceeded as follows. The reaction mixture
treated as above was extracted with hexanes (60 ml  3). The
organic layer was washed with brine (30 ml  2), dried over
anhydrous MgSO4, and concentrated under reduced pressure. The
residue was dissolved in 20 ml n-hexane, stored at À20 8C
overnight. Precipitate that formed was filtered off to afford
5,11-diphenyl-6-(trifluoromethyl)-12-[(trimethylsilyl)oxy]-
5,6,11,12-tetrahydro-6,12-epoxydi-benzo[b,f][1,5]diazocine (6a)
(150 mg, 0.28 mmol, 6%) as a yellowish powder. Mp 168 8C.1H
4.3. Synthesis of 1,1,1,3,3,3-hexafluoro-2-[2-
(methylamino)phenyl]propan-2-ol (3a) by reaction of Ruppert‘s
reagent with compound 2a
NMR (600.21 MHz, CDCl3): d 7.5–7.2 (12H, m, Ar), 7.10 (1H, td,
J1 = 7.6 Hz, J2 = 1.1 Hz, Ar), 6.97 (1H, td, J1 = 7.6 Hz, J2 = 1.5 Hz, Ar),
6.81 (1H, t, J = 7.8 Hz, Ar), 6.77 (1H, t, J = 7.8 Hz, Ar), 6.58 (1H, d,
J = 8.4 Hz, Ar), 6.20 (1H, d, J = 8.1 Hz, Ar), 0.02 (9H, s, SiMe3). 13C
To a solution of compound 2a (0.36 g, 1.77 mmol), KF (30 mg,
0.52 mmol) and TBAB (168 mg, 0.52 mmol) in dry DMF (4 ml) was
added trimethyl(trifluoromethyl)silane (0.71 g, 5.00 mmol) drop-
wise at 0 8C under argon. After completion of addition, the reaction
mixture was allowed to warm to rt and stirred for 20 h. The
reaction was quenched with 10% aq HCl solution (10 ml) at 0 8C,
allowed to warm to rt, and stirred 2 h. The resulting solution was
extracted with EtOAc (15 ml  3). The organic layer was washed
with brine (15 ml  2), dried over anhydrous MgSO4, and
concentrated under reduced pressure. The residue was purified
by preparative TLC on silica gel (toluene/hexanes/EtOAc = 2:1:1) to
afford compound 3a (266 mg, 55% yield) as a yellowish powder.
NMR (150.93 MHz, CDCl3): d 145.1, 143.9, 142.7, 142.2, 132.7,
132.1, 131.1, 129.6, 128.9, 128.8, 128.5, 128.0, 126.8, 126.4, 126.0,
1
122.9 (q, JC,F = 286 Hz, CF3), 120.3, 119.7, 119.5, 119.4, 117.2,
2
101.6, 88.8 (q, JC,F = 30 Hz, C–CF3), 0.9 (SiMe3).19F NMR (282.38
MHz, CDCl3):
d
À71.84 (s, 3F, CF3). EIMS 70 eV, m/z: 532 [M]+ (27),
517 [MÀCH3]+ (12), 463 [MÀCF3]+ (22), 440 [MÀCH3ÀPh]+ (16),
373 [MÀCF3ÀCH3ÀPh+2H]+ (47), 345 [MÀCH3À2PhÀF+H]+ (19),
324
[MÀCH3À2PhÀ2F+H]+
(100).
Anal.
Calcd
for
C30H27F3N2O2Si: C, 67.65; H 5.11; N 5.26. Found C, 67.25; H,
4.98; N, 5.02.
The filtrate was concentrated under reduced pressure, and the
residue was purified by column chromatography (toluene/hexanes
1:25) on silica gel to afford ethanone 5a. Orange oil [22b]. Yield
4.4. Synthesis of 2,2,2-trifluoro-1-[4-(methylamino)biphenyl-3-
74%. 1H NMR (300.13 MHz, CDCl3):
d 10.31 (1H, br s, NHPh), 7.92
yl]ethanone (2e) by Suzuki coupling.
(1H, dqd, J1 = 8.4 Hz, 5JH,F = 2.1 Hz, J2 = 1.4 Hz, Ar), 7.47 (3H, m, Ar),
7.30 (4H, m, Ar), 6.83 (1H, ddd, J1 = 8.4 Hz, J2 = 7.0 Hz, J3 = 1.1 Hz,
Ar). 13C NMR spectral data completely agreed with the data
Bromide 2b (630 mg, 2.23 mmol), phenylboronic acid (410 mg,
3.35 mmol), tricyclohexyl phosphine (Cy3P) (60 mg, 0.21mmol)
and K3PO4*H2O (1.94 g, 8.43 mmol) were combined in water
(2.1 ml) and toluene (15 ml). To the mixture obtained was added
Pd(OAc)2 (25 mg, 0.11 mmol) and reaction stirred for 1.5 h at rt
under argon. When the reaction completed, the reaction mixture
was filtered through Celite, washed with toluene (40 ml) and water
(10 ml). The organic layer was washed with a satd NaHCO3
solution (20 ml  2), dried over anhydrous MgSO4, and concen-
trated under reduced pressure. The residue was purified by
preparative TLC on silica gel (toluene/hexanes = 3:7) to afford
compound 2e (590 mg, 2.12 mmol, 95% yield) as an orange
reported in the literature [12]. 19F NMR (282.38 MHz, CDCl3):
d
À67.87 (d, J = 2.1 Hz, 3F, CF3).
4.5.2. 2,2,2-Trifluoro-1-{2-[(4-
methoxyphenyl)amino]phenyl}ethanone (5b)
The reaction time was 5 h. The isolation proceeded as follows.
When stirred, the reaction mixture treated as above formed a
precipitate, which was filtered off, washed with water (50 ml) and
dried in vacuum to give 5b. Yellow powder. Yield 83%. Mp 80 8C,
ref. [12] mp 77–78 8C. 1H NMR (600.21 MHz, CDCl3):
d 10.15 (br s,
1H, NHPh), 7.85 (d, J = 7.8 Hz, 1H, Ar), 7.37 (t, J = 7.8 Hz, 1H, Ar),
7.21 (d, J = 8.7 Hz, 2H, Ar), 7.00 (d, J = 7.8 Hz, 1H, Ar), 6.97 (d,
J = 8.7 Hz, 2H, Ar), 6.73 (d, J = 7.8 Hz, 1H, Ar), 3.86 (s, 3H, OMe). 13
C
powder. Mp 86–87 8C.1H NMR (300.13 MHz, CDCl3):
d 8.82 (1H,
br s, NHMe), 8.06 (1H, pent, J = 2.0 Hz, Ar), 7.83 (1H, dd, J1 = 9.1 Hz,
J2 = 2.2 Hz, Ar), 7.59 (2H, m, Ar), 7.51 (2H, m, Ar), 7.40 (1H, m, Ar),
6.91 (1H, d, J = 9.1 Hz, Ar), 3.11 (3H, d, J = 5.1 Hz, NHMe). 13C
NMR spectral data completely agreed with the data reported in the
literature [12]. 19F NMR (282.38 MHz, CDCl3):
CF3).
d
À67.84 (br. s, 3F,
2
(100.15 MHz, CDCl3):
d
180.4 (q, JC,F = 33 Hz, C(O)CF3), 153.5,
3
139.6, 136.1, 129.8 (q, JC,F = 6 Hz, CC(O)CF3), 128.8, 127.7, 126.7,
126.0, 117.2 (q, JC,F = 291 Hz, CF3), 112.4, 110.7, 29.4 (NHMe).19
F
4.5.3. 2,2,2-Trifluoro-1-{2-[(4-fluorophenyl)amino]phenyl}ethanone
(5c)
1
NMR (282.38 MHz, CDCl3):
d
À67.51 (d, 5JH,F = 2.2 Hz, 3F, CF3). EIMS
70 eV, m/z: 280 [M+H]+ (14), 279 [M]+ (66), 211 [M+HÀCF3]+ (17),
The reaction time was 5 h.The isolation proceeded as follows.
The reaction mixture was treated as above, extracted with hexanes
(60 ml  3). The organic layer was washed with brine (30 ml  2),
dried over anhydrous MgSO4, and concentrated under reduced
pressure. The residue was purified by column chromatography
(PhH/hexanes/EtOAc 1:40:5) on silica gel to afford ethanone 5c.
Yellow powder. Yield 67%. Mp 65–66 8C. 1H NMR (300.13 MHz,
210
[MÀCF3]+
(100),
182
[MÀCF3ÀCO]+
(33),
165
[MÀCF3ÀCOÀNH3]+ (33). Anal. Calcd for C15H12F3NO: C, 64.51;
H 4.33; N 5.02. Found C, 64.35; H, 4.37; N, 5.23.
4.5. General procedure for synthesis of compounds 5a–d
To a solution of the corresponding 1-aryl-2H-3,1-benzoxazine-
2,4(1H)-dione (N-arylisatoic anhydride) (4a–d) (10 mmol), KF
(174 mg, 3 mmol) and TBAB (967 mg, 3 mmol) in dry DMF (20 ml)
CDCl3):
7.30 (2H, m, Ar), 7.14 (3H, m, Ar), 6.82 (1H, ddd, J1 = 8.4 Hz,
J2 = 6.9 Hz, J3 = 1.0 Hz, Ar). 13C (150.93 MHz, CDCl3):
181.1 (q,
d 10.19 (1H, br s, NHAr), 7.92 (1H, m, Ar), 7.45 (3H, m, Ar),
d

A.F. Shidlovskii et al. / Journal of Fluorine Chemistry 143 (2012) 272–280
279
1
2JC,F = 33 Hz, C(O)CF3), 160.6 (d, JC,F = 245 Hz, C–F), 151.8, 137.0,
solution (30 ml). The organic layer was washed with brine
(20 ml  2), dried over anhydrous MgSO4, and concentrated under
reduced pressure. The residue was purified by recrystallization
from acetone to give acridine 8a–d.
4
3
134.7 (d, JC,F = 3 Hz), 132.0 (q, JC,F = 4 Hz, CC(O)CF3), 126.8 (d,
3JC,F = 9 Hz), 117.1 (q, JC,F = 291 Hz, CF3), 116.9, 116.5 (d,
1
2JC,F = 27 Hz), 114.1, 111.7. 19F {1H} NMR (282.38 MHz, CDCl3):
d
À67.91 (s, 3F, CF3), À114.86 (s, 1F, 4-FC6H4). EIMS 70 eV, m/z: 284
[M+H]+ (14), 283 [M]+ (87), 215 [MÀCF3]+ (16), 214 [MÀCF3]+
(100), 186 [MÀCF3ÀCO]+ (8), 185 [MÀCF3ÀCOÀH]+ (35), 166
[MÀCF3ÀCOÀHF]+ (17). Anal. Calcd for C14H9F4NO: C, 59.37; H
3.20; N 4.95. Found C, 59.05; H, 3.18; N, 5.12.
4.6.1. 9-(Trifluoromethyl)acridine (8a)
Reaction time 72 h. Yellowish powder. Yield 86%. Mp 108 8C
(acetone). 1H NMR (300.13 MHz, CDCl3):
d 8.56 (2H, br. d, J = 9.0 Hz,
H-1, H-8), 8.36 (2H, d, J = 9.0 Hz, J = 1.0 Hz, H-4, H-5), 7.89 (2H, dt,
J = 9.0 Hz, J = 1.0 Hz, H-3, H-6), 7.64 (2H, ddd, J1 = 9.0 Hz,
4.5.4. 2,2,2-Trifluoro-1-(2-{[4-
J2 = 7.0 Hz, J3 = 1.0 Hz, H-2, H-7). 13C (150.93 MHz, CDCl3):
d
2
(diphenylmethyl)phenyl]amino}phenyl)ethanone (5d)
148.5, 130.3, 130.1, 129.8 (q, JC,F = 28 Hz, 9CCF3), 128.2, 128.1,
The reaction time was 10 h. The isolation proceeded as follows.
The reaction mixture was treated as above, extracted with hexanes
(60 ml  3). The organic layer was washed with brine (30 ml  2),
dried over anhydrous MgSO4, and concentrated under reduced
pressure. The residue was purified by column chromatography
(hexanes/toluene/EtOAc 7:2:1) on silica gel to afford compound
125.5 (q, 1JC,F = 279 Hz, CF3), 124.3 (q, 4JC,F = 6 Hz, C-1, C-8), 122.7.
19F NMR (282.38 MHz, CDCl3):
d
À48.93 (s, 3F, CF3). EIMS 70 eV, m/
z: 248 [M+H]+ (18), 247 [M]+ (100), 198 [M+HÀCF2]+ (11), 197
[MÀCF2]+ (64), 178 [MÀCF3]+ (9). Anal. Calcd for C14H8F3N: C,
68.02; H 3.26; N 5.67. Found C, 67.95; H, 3.37; N, 5.42.
5d. Yellow–orange oil. Yield 77%. 1H NMR (300.13 MHz, CDCl3):
10.30 (1H, s, NHAr), 7.91 (1H, m, Ar), 7.51–7.21 (16H, m, Ar), 6.82
(1H, m, Ar), 5.64 (1H, s, CHPh2).13C (75.46 MHz, CDCl3):
180.9 (q,
2JC,F = 33 Hz, C(O)CF3), 151.3, 143.7, 141.3, 137.0, 136.9, 132.0 (q,
3JC,F = 4 Hz, CC(O)CF3), 130.6, 129.4, 128.4, 126.5, 124.2, 117.2 (q,
1JC,F = 291 Hz, CF3), 116.8, 114.6, 111.8, 56.4. 19F NMR (282.38 MHz,
d
4.6.2. 2-Methoxy-9-(trifluoromethyl)acridine (8b)
Reaction time 120 h. Green powder. Yield 64%. Mp 91–92 8C
d
(acetone). 1H NMR (600.21 MHz, CDCl3):
d 8.39 (1H, d, J = 9.0 Hz,
Ar), 8.25 (1H, d, J = 9.0 Hz, Ar), 8.15 (1H, d, J = 9.4 Hz, Ar), 7.73 (1H,
dd, J1 = 6.6 Hz, J2 = 9.0 Hz,Ar), 7.62 (1H, ddd, J1 = 6.6 Hz, J2 = 9.0 Hz,
J3 = 1.1 Hz), 7.54 (1H, br. s, Ar), 7.46 (1H, dd, J1 = 6.6 Hz,
J2 = 9.0 Hz,Ar), 3.97 (3H, s, OCH3). 13C (150.93 MHz, CDCl3):
d
CDCl3):
d
À67.85 (br. s, 3F, CF3). EIMS 70 eV, m/z: 432 [M+H]+ (32),
431 [M]+ (100), 413 [M+HÀF]+ (29), 363 [M+HÀCF3]+ (29), 362
[MÀCF3]+ (90), 354 [MÀPh]+ (80), 284 [MÀHCF3ÀPh]+ (24). Anal.
Calcd for C27H20F3NO: C, 75.16; H 4.67; N 3.25. Found C, 75.44; H,
4.89; N, 3.42.
158.7, 146.7, 146.0, 131.9, 130.4, 128.8, 128.2, 126.8 (q,
1
2JC,F = 29 Hz, C-9), 125.8 (q, JC,F = 277 Hz, CF3), 125.5, 124.1,
4
4
123.8 (q, JC,F = 6 Hz, C-8), 123.1, 99.9 (q, JC,F = 6 Hz, C-1), 55.5.
19F NMR (282.38 MHz, CDCl3):
d
À49.73 (s, 3F, CF3). EIMS 70 eV, m/
By the further eluation of the column was isolated 2-(2-{[4-
(diphenylmethyl)phenyl]amino}phenyl)-1,1,1,3,3,3-hexafluoro-
propan-2-ol (7d). Brown oil, yield 5%. 1H NMR (600.21 MHz,
z: 278 [M+H]+ (18), 277 [M]+ (100), 247 [MÀOCH2]+ (8), 234
[MÀCOCH3]+
(81),
214
[MÀHFÀCOCH3]+
(11),
184
[MÀCF2ÀCOCH3]+ (16). Anal. Calcd for C15H10F3NO: C, 64.98; H
CDCl3):
d
7.74 (1H, d, J = 7.7 Hz, Ar), 7.45 (1H, dd, J1 = 7.5 Hz,
3.64; N 5.05. Found C, 64.63; H, 3.47; N, 5.66.
J2 = 7.0 Hz, Ar), 7.38 (1H, dd, J1 = 7.7 Hz, J2 = 7.5 Hz, Ar), 7.33–7.14
(11H, m, Ar), 7.05 (2H, d, J = 8.1 Hz, Ar), 6.76 (2H, d, J = 8.1 Hz, Ar),
4.6.3. 2-Fluoro-9-(trifluoromethyl)acridine (8c)
5.53 (1H, s, CHPh2). 13C (150.93 MHz, CDCl3):
d
143.8, 143.4, 143.2,
Reaction time 168 h. Yellowish powder. Yield 53%. Mp 82–83 8C
138.7, 131.1, 130.5, 130.1, 129.4, 128.7, 128.4, 127.3, 126.4, 125.6,
(acetone). 1H NMR (600.21 MHz, CDCl3):
d 8.45 (1H, d, J = 9.0 Hz,
1
2
123.1 (q, JC,F = 290 Hz, CF3), 118.9, 80.0 (sept, JC,F = 31 Hz,
C(CF3)2), 56.2.19F NMR (282.38 MHz, CDCl3):
Ar), 8.31 (1H, dd, J = 9.0 Hz, J = 6.2 Hz, Ar), 8.29 (1H, d, J = 9.0 Hz Ar),
8.10 (1H, d, JH–F = 11.5 Hz, Ar), 7.83 (1H, dd, J1 = 6.6 Hz, J2 = 9.0 Hz,
Ar), 7.70 (1H, ddd, J1 = 6.6 Hz, J2 = 9.0 Hz, J3 = 1.1 Hz, Ar), 7.64 (1H,
d
À74.12 (s, 6F,
(CF3)2). EIMS 70 eV, m/z: 502 [M+H]+ (33), 501 [M]+ (99), 424
[MÀPh]+ (100), 336 [MÀPhÀCF3ÀH2OÀH]+ (25), 229
[MÀ2PhÀH2O]+ (43). Anal. Calcd for C28H21F6NO: C, 67.06; H
4.22; N 2.79. Found C, 67.35; H, 4.37; N, 2.49.
m, Ar). 13C (150.93 MHz, CDCl3):
d
161.1 (d, JC,F = 252 Hz, C–F),
1
4
4
148.3 (d, JC,F = 3 Hz), 146.4, 134.7 (d, JC,F = 3 Hz), 132.0 (q,
3JC,F = 4 Hz, CC(O)CF3), 133.5 (d, JC,F = 10 Hz), 128.9 (dq,
3
4
1
By the further eluation of the column was isolated 2-
(diphenylmethyl)-9-(trifluoromethyl)acridine (8d). Brown pow-
2JC,F = 25 Hz, JC,F = 8 Hz, C-9), 128.8, 125.4 (q, JC,F = 279 Hz, CF3),
4
2
123.4 (q, JC,F = 6 Hz), 123.1, 123.0, 121.9 (d, JC,F = 28 Hz), 107.2
der. Yield 5%. Mp 131–132 8C. 1H NMR (600.21 MHz, CDCl3):
d
8.46
(dq, JC,F = 28 Hz, JC,F = 7 Hz, C-1). 19F {1H} NMR (282.38 MHz,
2
4
(1H, d, J = 9.0 Hz, Ar), 8.31 (1H, d, J = 9.0 Hz, Ar), 8.23 (1H, d,
J = 9.0 Hz, Ar), 8.16 (1H, br. s, Ar), 7.82 (1H, dd, J1 = 6.6 Hz,
J2 = 9.0 Hz,Ar), 7.70 (1H, dd, J1 = 9.0 Hz, J2 = 1.3 Hz, Ar), 7.64 (1H,
ddd, J1 = 6.6 Hz, J2 = 9.0 Hz, J3 = 1.3 Hz), 7.37 (4H, m, Ar), 7.31 (2H,
m, Ar), 7.24 (4H, m, Ar), 5.81 (1H, s, CHPh2). 13C (150.93 MHz,
CDCl3):
d
À49.63 (s, 3F, CF3), À106.53 (s, 1F, 4-FC6H4). EIMS 70 eV,
m/z: 266 [M+H]+ (18), 265 [M]+ (100), 246 [MÀF]+ (9), 216
[M+HÀCF2]+ (11), 215 [MÀCF2]+ (72), 195 [MÀHÀCF3]+ (10). Anal.
Calcd for C14H7F4N: C, 63.40; H 2.66; N 5.28. Found C, 63.25; H,
2.47; N, 5.12.
CDCl3):
d 148.7, 148.3, 144.0, 142.7, 132.4, 130.6, 130.4, 129.7,
2
129.5, 129.1 (q, JC,F = 29 Hz, 9CCF3), 128.6, 128.1, 126.9, 125.5 (q,
4.6.4. 2-(Diphenylmethyl)-9-(trifluoromethyl)acridine (8d)
1JC,F = 279 Hz, CF3), 124.3 (q, JC,F = 6 Hz), 123.8 (q, JC,F = 6 Hz),
123.0, 122.7, 57.5.19F NMR (282.38 MHz, CDCl3):
CF3). EIMS 70 eV, m/z: 414 [M+H]+ (28), 413 [M]+ (100), 412
[MÀH]+ (61), 336 [MÀPh]+ (35), 266 [MÀPhÀHCF3]+ (31). Anal.
Calcd for C27H18F3N: C, 78.44; H 4.39; N 3.39. Found C, 78.73; H,
4.47; N, 3.12.
Reaction time 72 h. Brown powder. Yield 83%.
4
4
d
À48.98 (s, 3F,
4.7. X-ray diffraction experiment
Yellow single crystal samples of 6a in the form of thin plates
suitable for the X-ray study were obtained by slow evaporation of
solution of 6a in diethyl ether. At room temperature (294K),
crystals 6a (C30H27F3N2O2Si) are triclinic, space group P-1:
4.6. General procedure for synthesis of acridines 8a–d
˚
˚
˚
3
a = 9.169(3) A, b = 11.706(4) A, c = 13.853(5) A,
a = 86.544(8),
˚
To a solution of ethanone 5a–d (3 mmol) in CHCl3 (7 ml) was
added TFA (4.0 g) and reaction mixture stirred for the specified
time. The solvents were removed under reduced pressure, the
residue was diluted by EtOAc (50 ml) and a satd aq NaHCO3
b
= 73.189(7),
g
= 67.937(7), V = 1317.1(8) A , Z = 2, dcalc
= 0.141 mmÀ1. The 7660 reflections were collect-
˚
=
1.343 g cmÀ3
,
m
ed at SMART APEX2 CCD difractometer (l(Mo-Ka) = 0.71073 A,
graphite monochromator,
v-scans, 2u < 60) at 294 K. An analysis

280
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structure was solved by the direct methods and refined by the full-
matrix least-squares procedure against F2 in anisotropic approxi-
mation. The 5046 independent reflections (R(int) = 0.0376) were
used in the refinement procedure that was converged to
wR2 = 0.1066 calculated on Fh2kl (GOF = 0.987, R1 = 0.0513 calculated
(b) M. Patel, S.S. Ko, R.J. McHugh Jr., J.A. Markwalder, A.S. Srivastava, B.C. Cordova,
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bond lengths, bond angles and thermal parameters have been
deposited at the Cambridge Crystallographic Data Centre (CCDC).
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif. Any request to the CCDC should quote the full literature
citation and the reference number 876706.
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Acknowledgment
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This work was financially supported by the Russian Foundation
for Basic Research (Project ofi-ts no. 08-04-13562).
Appendix A. Supplementary data
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