General and efficient synthesis of polyfluorinated 2-aminotolans and 2-arylindoles

Article abstract of DOI:10.1016/j.jfluchem.2016.06.010

It was established here that cross-coupling of polyfluorinated 2-iodoanilines with arylacetylenes in MeCN in the presence catalytic amounts of Pd(PPh₃)₂Cl₂, CuI and Et₃N produces the corresponding 2-aminotolans although their yields are decreased from 98% to 40% with increasing fluorination of the substrates. It was shown that the 2-aminotolans with six or fewer fluorine atoms in their rings can be heterocyclised by heating in ethanol containing p-TSA to produce the corresponding polyfluorinated indoles. Cyclisation of tolans containing larger numbers of fluorine atoms in their rings proceeds most efficiently in the presence of KOH, resulting in 2-phenylindoles containing the current maximum of eight fluorine atoms.

Full text of DOI:10.1016/j.jfluchem.2016.06.010

Journal of Fluorine Chemistry 188 (2016) 85–98
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
General and efficient synthesis of polyfluorinated 2-aminotolans and
2
-arylindoles
1
Larisa V. Politanskaya*, Vitalij D. Shteingarts , Evgeny V. Tretyakov
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Ac. Lavrentiev Ave., 9,
6
30090 Novosibirsk, Russian Federation
A R T I C L E I N F O
A B S T R A C T
Article history:
Received 9 May 2016
It was established here that cross-coupling of polyfluorinated 2-iodoanilines with arylacetylenes in
Received in revised form 14 June 2016
Accepted 18 June 2016
Available online 20 June 2016
MeCN in the presence catalytic amounts of Pd(PPh ) Cl , CuI and Et N produces the corresponding 2-
3
2
2
3
aminotolans although their yields are decreased from 98% to 40% with increasing fluorination of the
substrates. It was shown that the 2-aminotolans with six or fewer fluorine atoms in their rings can be
heterocyclised by heating in ethanol containing p-TSA to produce the corresponding polyfluorinated
indoles. Cyclisation of tolans containing larger numbers of fluorine atoms in their rings proceeds most
efficiently in the presence of KOH, resulting in 2-phenylindoles containing the current maximum of eight
fluorine atoms.
Keywords:
Polyfluorinated compounds
Sonogashira cross-coupling
Retro-Favorsky reaction
Heterocyclization
Indoles
ã 2016 Elsevier B.V. All rights reserved.
1. Introduction
inhibitors [17–19]. It is also obvious that despite much interest in
the chemistry of indole, its polyfluorinated derivatives remain a
An indole moiety is present in numerous substances produced
naturally in living organisms and in a vast array of biologically
active compounds and pharmaceutical agents. For this reason,
indole is referred to as one of the so-called privileged structures,
poorly studied class of compounds. Meanwhile, it is known that
introduction of a fluorine atom into biologically active substances
is an effective way to alter their therapeutic potency [20–22].
Additionally, the presence of several fluorine atoms in an indole
nucleus and its substituents opens up new opportunities to obtain
polyfluorinated indole derivatives and heterocyclic systems
containing indole moieties. All these observations motivated us
to conduct the present study on the synthesis of a large series of
polyfluorinated 2-arylindoles, including the syntheis of octafluoro-
phenylindole with the current maximal extent of fluorination.
whose presence in more complex systems means
a high
probability that such compounds will have well-pronounced
and targeted biological effects [1]. Accordingly, increased attention
is given to research on the synthesis of various polyfunctional
indole derivatives and on their biological and pharmaceutical
activities. According to the ‘Web of Science’, more than 23000
articles were published only in the last five years on the subject of
production of biologically active compounds of the indole series.
Because it is not practical to cite all the works deserving attention,
we can mention a few selected publications illustrating the range
of biological effects of some indole derivatives. For example, it is
worthwhile to consider the series of substituted 2-arylindoles [2],
considering that it contains effective antineoplastic agents [3–7]
and modulators of tubulin dynamics [7,8] together with proges-
terone receptors [9], antioxidants [10], antibacterial [11–14] and
antimicrobial [15] drugs, anti-inflammatory, analgesic and antipy-
retic medicines [16] as well as selective cyclooxygenase (COX-2)
2. Results and discussion
The basic methods for synthesis of the indole nucleus comprise
heterocyclisation of 2-aminotolans [23,24]; this reaction, in the
case of polyfluorinated compounds, may be promoted specifically
by NaAuCl
bases such as KOH, Et
4
ꢀ
H
2
O [25], Pd(II) salts [26] or p-TSA [27] as well as by
NF [26] and EtONa [28]. To construct
4
aminotolans, it is best to use the well-known reaction of cross-
coupling of terminal acetylenes and iodo-arenes [29]. Thus, this
approach involves the retrosynthesis of polyfluorinated 2-arylin-
doles (compound 1, Scheme 1) from 2-aminotolans (compound 2)
prepared from fluorinated 2-iodoanilines (compound 3) and
ethynylarenes (compound 4, Scheme 1). Acetylene derivatives 5
may serve as precursors of the latter, which are produced by cross-
coupling of iodo-arenes 6 and 2-methylbut-3-yn-2-ol (Scheme 1).
*
Corresponding author.
E-mail address: plv@nioch.nsc.ru (L.V. Politanskaya).
Deceased.
1
http://dx.doi.org/10.1016/j.jfluchem.2016.06.010
022-1139/ã 2016 Elsevier B.V. All rights reserved.
0

8
6
L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
ethynyltetrafluoroaniline (4c). This result is due to the low
Fk
reactivity of 4c, which prevents the full extent of conversion of
the initial compound, even when the reaction time is doubled. The
fact that the polyfluorination of substrates decreases the reactivity
was confirmed by an attempt to perform the opposite type of the
cross-coupling reaction between 4-iodoaniline 6c and 2-ethynyl-
I
Fk
N
H
Fn
NH2
Fn
Fn
NH2
1
3
3
,5,6-trifluoro-4-(trifluoromethyl)aniline (4d). In this case, even
2
Fk
after 6 h, we achieved only 25% conversion of ethynylarene 4d into
the target 2-aminotolan (2dc), with a yield of 19% after isolation.
Fk
Fk
2
ꢁ
,3,5,6-Tetrafluoroaniline (8) was a by-product with a yield of
20%, while unreacted compounds 4d and 6c were isolated from
the reaction mixture with yields of 25% and 33%, respectively
Scheme 5). Therefore, the cross-coupling of polyfluorinated
I
5
HO
4
6
(
Scheme 1. Retrosynthesis of polyfluorinated 2-arylindoles.
compounds 4d and 6c is noticeably slower than that of the less
fluorinated substrates, and this reaction is complicated by parallel
processes such as deiodination of compound 6c.
The successful synthesis of polyfluorinated 2-aminotolans 2
allowed us to proceed to the main task of the study, i.e.,
investigation of the heterocyclisation of tolans 2 into indoles. It is
known that this process may be implemented through activation
of either electrophilic or nucleophilic functions of the molecule.
The first type of heterocyclisation mentioned can be induced by
This strategy to obtain polyfluoroindoles 1 seemed fairly reliable.
Nevertheless, before the experiments were carried out, there had
been some doubts about the feasibility of smooth cleavage of
acetylenic alcohols 5 bearing polyfluorinated aromatic rings and
about heterocyclisation of polyfluorinated 2-aminotolans 2.
2
.1. Synthesis of polyfluorinated 4-iodoanilines and 4-ethynylanilines
2
transition metal compounds (method A, Fig. 1), e.g. PdCl [26], or
A decision was made to generate a series of 4-iodoanilines
fluorinated to various degrees: 3-fluoro- (6a), 2,5-difluoro- (6b)
and 2,3,5,6-tetrafluoro-4-iodoaniline (6c). Mono-fluoro-derivative
proton donor acids (method B), e.g. p-TSA [27], due to formation of
a partial positive charge on the carbon atom of the substrate’s
triple bond. The second type heterocyclisation involves activation
6
a was described earlier [30]. Compound 6b was synthesised here
with a 91% yield via iodination of 2,5-difluoroaniline in an I
NaHCO /water system. Tetrafluorinated substrate 6c was produced
of the amine group under the influence of bases (method
32].
In our study, the initial emphasis was on heterocyclisation
E, Fig. 1)
2
/
[
3
as shown in Scheme 2: by amination of pentafluoro(trifluoro-
methyl)benzene, removal of the trifluoromethyl group in 2,3,5,6-
tetrafluoro-4-(trifluoromethyl)aniline (7) and iodination of the
resulting 2,3,5,6-tetrafluoroaniline (8).
method B, which, judging by our experience [27], ensured a good
yield of 2-phenylindoles. Nevertheless, the experiments we
conducted revealed that an increased number of fluorine atoms
in the tolan scaffold significantly decreased the yield, whereas in
the case of substrates with the highest fluorine content, the
heterocyclisation did not occur at all. Therefore, we tested
alternative methods, A and C, to obtain polyfluorinated indoles,
4
-Iodoanilines 6 were cross-coupled with 2-methyl-3-butyn-2-
ol in MeCN in the presence of Pd(PPh Cl (4 mol%), CuI (9 mol%)
and Et N as catalysts to obtain acetylenic alcohols 5a–c with the
3
)
2
2
3
yield of 54–83% (Scheme 3). The resulting compounds (5a–c) were
cleaved via the retro-Favorsky reaction by the action of K?= in
benzene as described previously [31], thus producing fluorinated
ethynylarenes 4a–c with yields of 67–91%. The use of toluene in
this reaction resulted in a significant decrease in the yield of the
target products because of losses at the stage of isolation of volatile
compounds 4a–c.
2
using the systems of PdCl /MeCN and KOH/MeCN, respectively.
The data on the structure and yields of the reaction products under
various experimental conditions are summarised in Table 2.
Table 2 shows that the cyclisation of polyfluorinated 2-
aminotolans 2 containing six or fewer fluorine atoms proceeds
smoothly in the p-TSA/AlkOH system and in the PdCl
system, producing the target 2-arylindoles (1) with yields of 45–
1%. In addition, the acid-catalysed cyclisation of compounds
2
/MeCN
8
2
.2. Synthesis of polyfluorinated 2-(arylethynyl)anilines and 2-
arylindoles
containing one or two fluorine atoms in the peripheral ring
proceeded more effectively than the reaction catalysed by the
transition metal cation (the yield of 1 is higher with p-TSA than the
In this work, a representative series of polyfluorinated 2-
2
yield in the case of PdCl ; reaction 1 versus 2; reaction 3 vs. 4 in
iodoanilines 3a–d was used. It appeared that compounds 3a–d
smoothly entered into the Sonogashira cross-coupling reaction
with fluorinated ethynylarenes 4a–c, producing the target
polyfluorinated 2-aminotolans 2(a–d)(a–c). Meanwhile, small
amounts of the corresponding diynes (9a–c, Scheme 4) were
always detected among the reaction products. The yields of the 2-
aminotolans are presented in Table 1.
Table 2). On the other hand, as soon as the number of fluorine
atoms is increased, the situation is reversed. In the presence of p-
TSA, 2-aminotolans with four fluorine atoms in the peripheral ring
2
cyclised with a lower yield than in the presence of PdCl (reaction 5
vs. 6; reaction 9 vs. 10 in Table 2), or the heterocyclisation reaction
did not occur at all (reaction 13 vs. 14; reaction 19 vs. 21, Table 2).
With a larger number of fluorine atoms on both aromatic
fragments of a tolane, strong deactivation of the triple bond takes
Table 1 shows that the lowest yields of 2-aminotolans 2 were
obtained in the reaction between 2-iodoanilines 3b–d and
Scheme 2. Preparation of 4-iodoaniline 6c.

L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
87
Scheme 3. Synthesis of 4-ethynylanilines 4a–c.
Scheme 4. Sonogashira cross-coupling of iodoanilines 3a–d with ethynylarenes 4a–c.
place toward its interaction with a cation. This outcome is
especially well-pronounced in the case of conversion of 2dc into
distilled and kept over CaH
treated powder) were kept over P O
2
before use, KOH (ꢂ90%, flakes or heat-
. 2-Iodo-4,5-difluoroaniline
2 5
1
dc, which, under the influence of p-TSA, takes place only when the
(3a) [33], 2-iodo-3,4,6-trifluoroaniline (3b) [31], 2-iodo-3,5,6-
trifluoro-4-(trifluoromethyl)aniline (3d) [31], 3-fluoro-4-iodoani-
line (6a) [30], 2-ethynyl-3,5,6-trifluoro-4-(trifluoromethyl)aniline
(4d) [26], Pd(PPh ) Cl [34] were prepared according to literature
3 2 2
data. Other starting materials were obtained from commercial
suppliers and used without purification.
reaction is carried out at the boiling point of n-BuOH, whereas even
boiling the reaction mixture in EtOH for 6 h yielded no detectable
production of 1dc (reactions 19 and 20, Table 2). The method that
was found to be effective in this case consisted in carrying out the
reaction in the presence of PdCl or, even better, in K?=; both of
2
these approaches ensured production of polyfluoroindoles with an
acceptable yield (reactions 21 and 22, Table 2). For cyclisation of 2-
aminotolan 2cc, which contains eight fluorine atoms, base
catalysis appeared to be the most effective (reactions 13–15).
Analytical thin-layer chromatography (TLC) was performed on
Merck precoated silica gel 60 PF254 containing gypsum. Visualisa-
tion of the developed chromatograms was performed under UV
light. To obtain analytically pure samples, the synthesised
compounds were crystallized from hexane.
3
. Conclusion
NMR spectra were recorded on
a
Bruker Avance-300
1
19
(
300.13 MHz for
H
and 282.37 MHz for
F), Avance-400
1
19
13
We demonstrated feasibility of the synthesis of a wide
(400.13 MHz for H, 376.44 MHz for F and 100.62 MHz for C)
1
13
spectrum of polyfluorinated aromatic moieties of 2-aminotolans
and 2-arylindoles. This work may open up new opportunities for
the synthesis of novel biologically active compounds. It was
established that with the increased number of fluorine atoms in
and DRX-500 (500.13 MHz for H, 125.76 MHz for C) spectrom-
eters. Deuterochloroform (CDCl ) and acetone-d were used as
solvents, with residual CHCl = 7.26 ppm) or CDCl = 77.0
ppm) and acetone ( = 2.15 ppm) or acetone-d = 28.6 and
205.0 ppm) serving as internal standards. C 163.0 ppm) was
3
6
3
(d
H
3 C
(d
d
H
6 C
(d
the peripheral ring of 2-aminotolans, it is preferable to use PdCl
2
6 6 F
F (d
19
13
rather than p-TSA as the cyclising agent. Cyclisation of 2-
aminotolans 2dc and 2cc (containing the greatest numbers of
fluorine atoms) proceeds efficiently only under the conditions of
base catalysis (KOH/MeCN). The latter finding is a valuable
contribution to the field of synthesis of perfluoroindoles (currently,
a challenge for researchers).
used as an external reference ( F NMR). C NMR spectra were
registered with C ꢃꢃ H spin decoupling. Masses of molecular ions
were determined by HRMS on a DFS Thermo scientific instrument
(EI, 70 eV). Melting points were recorded on a Melter-Toledo FP81
Thermosystem apparatus. The infrared (IR) spectra were recorded
on a Bruker Vector 22 spectrometer (KBr or thin layer). The Raman
spectra were recorded on Ramanscope Senterra (25 mV, 785 nm).
Elemental analyses were performed on a Euro EA-3000 CHNS
analyser or a Carlo Erba 1106 CHN elemental analyser.
4. Experimental section
4
.1. General methods
The structures of all the polyfluorinated 2-(arylethynyl)anilines
and indoles prepared here were corroborated by their F, H and
C NMR, high-resolution mass spectrometry, and IR-spectroscopy
19
1
13
All the cross-coupling reactions were carried out in oven-dried
glassware in an argon atmosphere. All solvents were purified using
standard procedures and dried before use. Et N, MeCN were
data (see Supplementary data). Signals in the NMR spectra of
anilines 2 and indoles 1 were assigned on the basis of spin coupling
3

8
8
L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
Table 1
Synthesis of polyfluorinated 2-aminotolans 2(a–d)(a–c).
constants, which are typical for polyfluorinated benzenes
26,27,31].
[
4
4
0
.2. Synthetic procedures
.2.1. 2,3,5,6-Tetrafluoro-4-(trifluoromethyl)aniline (7)
1,2,3,4,5-Pentafluoro-6-(trifluoromethyl)benzene
(50 g,
.3 mol) and liquid ammonia were placed into the autoclave
(
volumetric capability 0.1 L). The reaction mixture was stirred at
room temperature (r.t.) for 6 h. After completion of ammonia
evaporation, H O (50 mL) was added to the residue. The reaction
product was separated by steam distillation. The distillate was
extracted with CH Cl ). After
(2 ꢄ100 mL) and dried (MgSO
evaporation of the solvent in vacuo, the title product (47 g, 93%)
2
2
2
4
1
19
was obtained as colorless liquid (the H and F NMR spectra agree
well with the literature data [35].
4
.2.2. 2,3,5,6-Tetrafluoroaniline (8)
Aniline 7 (15 g, 64 mmol) in concentrated H
stirred with a condenser at 150 C for 2 h. Then, H
2
SO
4
(50 mL) was
ꢅ
2
O (100 mL) was
added into the reaction flask, and the reaction product was
separated by steam distillation. The distillate was extracted with
CH
2
Cl
2
(3 ꢄ 50 mL), washed with H
2 4
O (50 mL) and dried (MgSO ).
After evaporation of the solvent in vacuo, the title product (7 g, 66%)
was obtained as light yellow liquid (the H and F NMR spectra
1
19
closely match the literature data [36]. max (KBr): 3501, 3414 (NH ),
664, 1618, 1524, 1400, 1269, 1178, 1090, 887, 804, 716 cm
NMR (300.13 MHz, CDCl ): = 6.36 (tt,1H, J 3 = 10.5; J 2 = 7.3 Hz,
); C NMR (100.62 MHz, CDCl
n
2
ꢃ1
1
1
; H
3
d
H
,
F
H F
,
13
H
ar), 4.03 (br s, 2H, NH
2
3
):
d
= 146.2
1
2
3
1
(
dm,
C
J 3,
F
= 243.4,
J
C
3,
= 12.6 Hz, C ), 136.3 (ddt, J 2, = 238.1,
F C F
2
2
2
3
1
J
C
2,
F
4,
F
F
= 16.2 Hz, C ), 126.7 (tt, J
1,
C F
= 14.3, J
C
1,
F
= 4.3 Hz, C ), 93.0 (t,
):
= ꢃ142.9 (m,
2, 3 = 24, J 2, = 7
6 3 4
; , found 165.0205. C H F N requires
2J
= 23.2 Hz, C ); F NMR (282.37 MHz, CDCl
4
19
d
C
3
3
2
F, J
3,
F
2 = 24, J
F
3,
H
= 10 Hz, F ), ꢃ163.3 (m, 2F, J
F
F
F
H
2
+
Hz, F ); HRMS (EI):
65.0196.
1
4
.2.3. 2,5-Difluoro-4-iodoaniline (6b)
A mixture of 2,5-difluoroaniline (0.5 g, 3.9 mmol), NaHCO
0.8 g, 9.8 mmol), I (2.5 g, 9.8 mmol) and H O (50 mL) was stirred
at r.t. for 2 h. Than Na SO (1 g, 8 mmol) was added, and the
reaction mixture was extracted with CH
combined organic layers were washed with H
MgSO
tion of the solvent was performed in vacuo to obtain 6b (0.9 g, 91%)
3
(
2
2
2
3
2
Cl
2
(2 ꢄ 50 mL). The
2
O (50 mL), dried
(
4 2 3
) and purified by flash chromatography on Al O . Evapora-
1
13
as brown solid (the H and C NMR spectra closely agree with the
literature data [37]); max (KBr): 3464, 3379, 3042, 2926, 2855,
632, 1501, 1414, 1323, 1298, 1234, 1184, 1167, 864, 837, 795, 733,
n
1
5
ꢃ1
1
96, 444 cm
3, 2 = 9.9, J
Hz, H ), 3.91 (br s, 2H, NH
;
H NMR (500.13 MHz, CDCl
3
):
6,
); C NMR (125.76 MHz, CDCl
d
= 7.27 (dd, 1H,
5 = 8.7, J 6, 2 = 7.7
):
3
J
H
F
H
3,
F
5 = 5.6 Hz, H ), 6.52 (d, 1H, J
H
F
H
F
6
13
2
3
2
1
5
1
d
= 158.0 (d, J
C
5,
F
5 = 239.1 Hz, C ), 147.4 (d, J
C
2,
F
2 = 239.6 Hz, C ),
2
3
1
2
135.7 (dd,
J
C
1,
F
2 = 14.7,
J
C
1,
F
5 = 10.6 Hz, C ), 123.8 (dd,
J
C F
3, 2 =
3
3
2
3
2
2.8,
J
C
3,
C ), 62.8 (dd,
282.37 MHz, CDCl
F
5 = 3.5 Hz, C ), 102.7 (dd,
J
C
6,
2 = 8.1 Hz, C );
= ꢃ101.5 (ddd, 1F, J 5, 2 = 13.4, J
3 = 5.6 Hz, F ), ꢃ140.0 (ddd,1F, J 2, 5 = 13.4, J 2, 3 = 9.9, J
, found 254.9356. C IN requires
5 = 29.9, J 6, 2 = 3.7 Hz,
F C F
6
2
3
4
19
J
C
4,
):
F
5 = 29.1,
d
C
J 4,
F
F
NMR
(
3
F
F
F
5,
H
6 = 8.7,
5
J
F
5,
.7 Hz, F ); HRMS (EI):
54.9351.
H
F
F
F
H
F H
2, 6 =
2
+
7
2
;
6 4 2
H F
4
.2.4. 2,3,5,6-Tetrafluoro-4-iodoaniline (6c)
To a stirred solution of aniline 7 (3.0 g, 18 mmol) in dioxane
70 mL), we added fine-ground I (2.3 g, 9 mmol) and a solution of
O (12 mL). The reaction mixture was
O (50 mL) and
(3 ꢄ 50 mL). The combined organic layers
were washed with a saturated water solution of Na SO (50 mL)
(
2
3 2
HIO (3.2 g, 18 mmol) in H
refluxed for 4 h, cooled to r.t., poured into H
extracted with CH Cl
2
2
2
2
3

L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
89
Scheme 5. Sonogashira cross-coupling of iodoaniline 6c with ethynyl-3,5,6-trifluoro-4-(trifluoromethyl)aniline 4d.
Fig. 1. Different ways of activation of the 2-aminotolan molecule.
solution several times, then with H
After evaporation of the solvent in vacuo, the crude product was
2
O (100 mL) and dried (MgSO
4
).
31.3 (s, C|C ꢃꢃ C(CH
(dd, 1F, 2 = 10.8, J
193.0898. C11 12FNO requires 193.0897.
3
)
2
OH); 19F NMR (282.37 MHz, CDCl
5 = 7.7 Hz, F); HRMS (EI): ; , found
3
):
d
= ꢃ108.1
+
J
F
,
H
F
,
H
recrystallized from hexane to obtain the title product (5.0 g, 96%) as
H
ꢅ
ꢅ
light brown solid; m.p. 73.4–74.0 C (lit. data: 76.9–77.7 C [36]);
Found: C, 24.38; H, 0.75; N, 4.44. C IN requires C, 24.77; H,
max (KBr): 3483, 3389, 1655, 1491, 1173, 1101, 920,
[
H
6 2
F
4
4.2.5.2.
4-(4-Amino-2,5-difluorophenyl)-2-methylbut-3-yn-2-ol
0
.69; N 4.81%];
n
(5b). Preparative TLC (Merck precoated plates, hexane/ethyl
acetate, 5:1) was used to obtain 5b (160 mg, 83%) as light brown
ꢃ1
1
8
02 cm
;
H NMR (500.13 MHz, CDCl
C NMR (125.76 MHz, CDCl ): = 146.8 (dm, J
= 242.0, J
3
):
d
= 4.12 (br s, 2H, NH
2
);
=
1
3
1
2
3
d
3,
C F
= 240.9, J
C
3,
F
f
oil material; R 0.12; nmax (thin layer): 3364, 3225, 3080,2982,
3
1
2
2
1
1.8 Hz, C ), 136.0 (ddt, J
C
2,
F
C
2,
F
= 17.3 Hz, C ), 126.8 (tt,
2928, 2855, 2230, 1641, 1514, 1437, 1364, 1258, 1228, 1202, 1171,
2
3
1
2
4
19
ꢃ1
1
J
C
1,
282.37 MHz, CDCl
dm, 2F, J 2,
3 ꢆ16 Hz, F ); HRMS (EI):
IN requires 290.9168.
F
= 14.3, J
C
1,
F
= 3.5 Hz, C ), 55.1 (t, J
C
4,
F
= 28.1 Hz, C ); F NMR
1144, 1097, 962, 907, 876, 849, 733, 554, 438 cm
;
H NMR
5 = 6.3 Hz,
F
2 = 7.5 Hz, H ), 3.95 (br s, 2H,
3
(
(
C
3
):
d
= ꢃ122.4 (dm, 2F, J
F
3,
F
2 ꢆ16 Hz, F ), ꢃ157.6
(300.13 MHz, CDCl
H ), 6.42 (dd, 1H, J
3
):
d
= 6.97 (dd, 1H, J
5 = 10.1, J 6,
3 2
OH), 1.58 (s, 6H, C(CH ) OH); C NMR
H F H F
3, 2 = 11.0, J 3,
2
+
3
6
F
F
;
, found 290.9166.
H
6,
F
H
13
6
H F
2 4
NH
2
), 2.05 (br s, 1H, C(CH
3
)
2
1
5
(
100.62 MHz, CDCl
3
2
): = 159.9 (d, J
d
C
5,
F
5 = 245.9 Hz, C ), 146.6 (d,
1
2
3
1
4
.2.5. General procedure for synthesis of alkynylanilines 5(a,b)
Pd(PPh Cl (28 mg, 0.04 mmol), CuI (17 mg, 0.09 mmol) and
N (3 mL) were added to a stirred solution of iodoaniline 6
J
2,
C F
2 = 235.7 Hz, C ), 136.3 (dd, J
1,
C F
2 = 15.0, J
C
1,
F
5 = 11.2 Hz, C ),
2
3
3
2
3
)
2
2
118.7 (dd, J
C
3,
F
2 = 21.9, J
3,
C F
5 = 3.4 Hz, C ), 102.8 (dd, J
C
6,
F
5 = 27.1,
3
6
2
3
4
Et
3
J
6,
C F
2 = 4.1 Hz, C ), 99.4 (dd, J
C
4,
OH), 75.2 (d, J
OH), 65.6 (s, C|C ꢃꢃ C(CH OH), 31.3 (s, C|C ꢃꢃ C(CH
NMR (282.37 MHz, CDCl ): (ddd, 1F,
= ꢃ116.4
3 = 6.3 Hz, F ), ꢃ142.3 (ddd, 1F,
F
5 = 18.7, J
C
4,
F
2 = 8.8 Hz, C ), 96.9
= 2.2 Hz, C|C ꢃꢃ C
OH);
(
1 mmol) and 2-methylbut-3-yn-2-ol (168 mg, 2 mmol) in dry
(d, J
C
,
F
= 3.4 Hz, C|C ꢃꢃ C(CH
3
)
2
C F
,
MeCN (10 mL) at r.t. in an argon atmosphere. The mixture was
(CH
3
)
2
3
)
2
3 2
)
ꢅ
19
heated at 60 C for 1.5 h with stirring. The reaction mixture was
F
3
d
5
allowed to cool down to r.t., and CH
mixture was poured into H O (20 mL) and extracted with CH
3 ꢄ 50 mL). The combined organic layers were washed with H
20 mL) and dried (MgSO ). After evaporation of the solvent in
2
Cl
2
(10 mL) was added. The
J
J
F
5,
2,
F
F
2 = 14.2, J
5 = 14.2, J
F
5,
2,
H
H
6 = 10.1, J
3 = 11.0, J
NO requires 211.0803.
F
5,
H
2
+
2
2
Cl
2
F
F
F
2,
H
6 = 7.5 Hz, F ); HRMS (EI): ; ,
(
(
2
O
found 211.0805. C11
H
11
F
2
4
vacuo, the crude product was purified by preparative TLC to obtain
4.2.6. 4-(4-Amino-2,3,5,6-tetrafluorophenyl)-2-methylbut-3-yn-2-ol
(5c)
5.
Pd(PPh
were added to a stirred solution of 6c (1 g, 3.4 mmol) and 2-
methylbut-3-yn-2-ol (580 mg, 6.9 mmol) in dry Et N (15 mL) at r.t.
in an argon atmosphere. The mixture was stirred at r.t. for 88 h. The
reaction mixture was diluted with H O (20 mL) and extracted with
CH Cl
(3 ꢄ 50 mL). The combined organic layers were washed
with H O (20 mL) and dried (MgSO ). After evaporation of the
3 2 2
) Cl (95 mg, 0.14 mmol) and CuI (58 mg, 0.31 mmol)
4
.2.5.1.
4-(4-Amino-2-fluorophenyl)-2-methylbut-3-yn-2-ol
(
5a). Preparative TLC (Merck precoated plates, hexane/ethyl
acetate, 5:1 three times) was used to obtain 5a (114 mg, 54%) as
brown oil material; R 0.29; max (thin layer): 3362, 3235, 2982,
3
f
n
2
2
932, 2870, 2225, 1628, 1564, 1512, 1452, 1364, 1331, 1283, 1234,
2
2
ꢃ1
1
5
1
(
6
169, 1121, 962, 903, 843, 816, 627, 604, 554, 459 cm
300.13 MHz, CDCl ): = 7.12 (t, 1H, J 5, 5,
.29 (m, 2H, H , H ), 3.92 (br s, 2H, NH
;
H NMR
2
4
3
6
d
H
F
ꢆ J
H
H
6 ꢆ 9 Hz, H ), 6.35–
solvent in vacuo, the crude product was purified by preparative TLC
(Merck precoated plates, hexane/ethyl acetate, 5:1, twice) to obtain
2
2
), 2.38 (br s,1H, C(CH
3
)
2
OH),
13
1
.57 (s, 6H, C(CH
3
)
2
OH); C NMR (100.62 MHz, CDCl ): = 163.6 (d,
3
d
the title product (679 mg, 80%) as light brown solid; m.p. 91.9–
1
3
3
1
ꢅ
J
J
C
3,
C
5,
C
2,
F
F
F
= 249.0 Hz, C ), 148.3 (d,
J
C
1,
6,
F
= 10.9 Hz, C ), 134.0 (d,
= 2.3 Hz, C ), 101.5 (d,
92.5 C; R
f
0.34; [Found: C, 53.46; H, 3.98; N, 5.79. C11
9 4
H F NO
3
= 3.1 Hz, C ), 110.3 (d, 4J
5
6
C
F
requires C, 53.45; H, 3.67; N 5.67%];
n
max (KBr): 3397, 3331, 3267,
2J
= 24.5 Hz, C ), 100.0 (d,
2
2
J
4,
= 16.2 Hz, C ), 96.3 (s, C|C ꢃꢃ C
4
2984, 2939, 1661, 1609, 1504, 1458, 1379, 1366, 1315, 1221, 1196,
C
F
ꢃ1
(
CH
3
)
2
OH), 75.9 (s, C|C ꢃꢃ C(CH
3
)
2
OH), 65.5 (s, C|C ꢃꢃ C(CH
3
)
2
OH),
1167, 1115, 1011, 953, 868, 789, 716, 569, 557 cm
; nmax (Raman):

9
0
L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
Table 2
Synthesis of polyfluorinated 2-arylindoles 1(a–d)(a–c).
Reaction #
1
Substrate
Reagent
Solvent
EtOH
Time (h)
6
Product
Yield (%)
45
2aa
p-TSA
2
3
PdCl
p-TSA
2
MeCN
EtOH
6
7
12
63
2ab
4
5
PdCl
p-TSA
2
MeCN
EtOH
5
3
21
53
2ac
6
7
PdCl
2
MeCN
EtOH
4
7.5
67
78
2ba
2bb
2bc
p-TSA
p-TSA
p-TSA
8
9
EtOH
EtOH
3 or 4
60
45
8
1
11
0
PdCl
p-TSA
2
MeCN
EtOH
6
15
57
72
2ca
2cb
12
p-TSA
EtOH
1.5
73

L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
91
Table 2 (Continued)
Reaction #
Substrate
Reagent
Solvent
EtOH
Time (h)
5
Product
Yield (%)
13
2cc
p-TSA
n.r.
1
4
PdCl
KOH
p-TSA
2
MeCN
MeCN
n-BuOH
4.5
6
20
66
71
73
1
5
16
2da
1
18
7
PdCl
2
MeCN
EtOH
5
9
15
81
2db
2dc
p-TSA
p-TSA
p-TSA
19
EtOH
6
n.r.
2
0
n-BuOH
MeCN
MeCN
22
6
6
9
22
54
2
1
PdCl
KOH
2
2
2
237 (s), 1660, 1441, 1315, 866, 521 cm ; 1H NMR (300.13 MHz,
ꢃ1
4.2.7.1. 4-Ethynyl-2-fluoroaniline (4a). Preparative TLC (Merck
2
Acetone-d
H, C(CH
6
): 5.66 (br s, 2H, NH
2
), 4.66 (br s,1H, C(CH
3
)
d
2,
2
OH),1.54 (s,
= 147.1 (dm,
precoated plates, hexane/ethyl acetate, 6:1 twice) was used to
obtain 4a (271 mg, 67%) as brown oil material; R 0.35; nmax (thin
f
layer): 3480, 3391, 3292, 3225, 3067, 3046, 2926, 2853, 2106, 1632,
1605,1559,1510,1491,1450,1420,1369,1331,1298,1250,1171,1121,
13
6
3
)
2
OH); C NMR (100.62 MHz, Acetone-d ):
6
1
3
1
2
J
C
3,
F
3 = 243.8 Hz, C ), 135.9 (ddm, J
2,
C F
2 = 237.1,
J
C
F
3 = 15.5 Hz,
2
2
3
1
C ), 129.0 (tt, J
C
1,
F
2 = 14.4, J
C
1,
4,
F
3 = 4.0 Hz, C ), 104.0 (t, J
3 = 18.6 Hz, C ), 66.6 (t, J
C
,
,
F
= 3.4 Hz,
= 4.0 Hz,
2
4
ꢃ1
1
C|C ꢃꢃ C(CH
3
)
)
2
OH), 88.9 (t, J
C
F
C
F
1101, 961, 839, 743, 664, 604, 432 cm
CDCl ): = 7.21 (t, 1H, J 5, 5, 6 ꢆ 8 Hz, H ), 6.36–6.32 (m, 2H,
ꢆ J
H , H ), 3.91 (br s, 2H, NH
; H NMR (400.13 MHz,
5
C|C ꢃꢃ C(CH
3
2
OH), 64.6 (s, C|C ꢃꢃ C(CH
3
)
2
OH), 30.9 (s, C|C ꢃꢃ C
):
= ꢃ143.8 (dm,
3 ꢆ 21 Hz, F ); HRMS (EI):
NO requires 247.0615.
3
d
H
F
H
H
1
9
2
6
13
(
CH
3
)
2
OH); F NMR (282.37 MHz, Acetone-d
6
d
2
), 3.15 (s, 1H, C|CH); C NMR
3
2
1
3
2
;
F, J
F
3,
F
2 ꢆ 21 Hz, F ), ꢃ165.1 (dm, 2F, J
F
2,
F
(100.62 MHz, CDCl
3
):
d
= 164.4 (d,
J
C
3,
5,
2,
= 3.0 Hz C|CH), 77.7 (s, C|CH);
CDCl ): (dd,
= ꢃ111.0
5 = 7.6 Hz, F); HRMS (EI):
FN requires 135.0479.
F
= 249.9 Hz, C ), 148.8 (d,
+
3
4
= 11.0 Hz, C ), 134.6 (d, 3J
1
5
, found 247.0611. C11
9
H F
4
J
J
C
C
C
1,
6,
4,
F
C
F
= 3.3 Hz, C ), 110.3 (d,
6
2
2
F
= 2.6 Hz, C ), 101.4 (d,
J
C
F
= 24.4 Hz, C ), 99.4 (d,
2J
= 16.1 Hz, C ), 79.7 (d, J
4
,
C F
19
F
4.2.7. General procedure for synthesis of ethynylanilines 4(a–c)
F
Powdered KOH (336 mg, 6 mmol) was added to a stirred
solution of 5 (3 mmol) in benzene (25 mL) at r.t. The mixture was
heated under reflux with stirring for 4 h. The reaction mixture was
NMR
2 = 10.7, J
(282.37 MHz,
3
d
1F,
+
J
F
,
H
F
,
H
; , found 135.0476.
C H
8 6
2 2
allowed to cool down to r.t., diluted with CH Cl (20 mL) and
passed through Al (flash chromatography). Evaporation of the
solvent and purification of the crude product by preparative TLC
yielded 4.
2
O
3
4.2.7.2. 4-Ethynyl-2,5-difluoroaniline (4b). Preparative TLC (Merck
precoated plates, hexane/ethyl acetate, 5:1) was used to obtain 4b
(399 mg, 87%) as brown oil material; R 0.28; nmax (thin layer):
f

9
2
L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
+
3
493, 3379, 3314, 2953, 2922, 2853, 2112, 1742, 1641, 1524, 1462,
J
F
4, 3 = 11.1, J
F
5 = 22.5, J
F
4,
H
F H
4, ; , found
6 = 7.3 Hz, F11); HRMS (EI):
ꢃ1
1
1377, 1302, 1240, 1213, 1177, 876, 839, 721, 590 cm
;
H NMR
5 = 6.2 Hz,
2 = 7.5 Hz, H ), 3.99 (br s, 2H,
262.0707. C14H F N requires 262.0712.
9 3 2
(
400.13 MHz, CDCl
3
):
d
= 7.04 (dd, 1H, J
5 = 10.1, J 6,
H F H F
3, 2 = 11.0, J 3,
3
6
H ), 6.44 (dd, 1H, J
NH ), 3.16 (d, 1H, J
CDCl
H
6,
F
H
F
4.2.8.2. 2-((4-Amino-2,5-difluorophenyl)ethynyl)-4,5-difluoroaniline
(2ab). Preparative TLC (Merck precoated plates, hexane/ethyl
acetate, 5:1 twice) was used to obtain 2ab (262 mg, 88%) as light
13
2
H
,
F
= 0.5 Hz, C|C ꢃꢃ H); C NMR (125.77 MHz,
1
4
5
3
):
d
= 160.2 (dd, J
C
5,
F
5 = 246.6, J
C
5,
F
2 = 1.8 Hz, C ), 146.5 (dd,
1
4
2
2
ꢅ
J
C
2,
F
2 = 236.1,
J
C
1
2,
F
5 = 2.3 Hz, C ), 136.9 (dd,
J
1,
C F
2 = 14.8,
brown solid; m.p. 122.5 C (decomp.); R
2.80; N,10.08. C14
f
0.42; [Found: C, 60.23; H,
requires C, 60.01; H, 2.88; N,10.00%]; n
3J
5 = 11.3 Hz, C ), 119.1 (dd, 2J
3,
2 = 4.1 Hz, C ), 98.6 (dd, J
= 3.3 Hz, C|C ꢃꢃ H), 76.7 (d,
):
= ꢃ116.2
3 = 6.2 Hz, F ), ꢃ142.1 (ddd,
2 = 22.0,
3
J
3,
C F
5 = 3.4 Hz, C ),
3
H
F
8 4
N
C
1,
F
C
F
2
max
2
3
6
2
1
J
02.7 (dd, J
C
6,
F
5 = 27.0, J
2 = 8.6 Hz, C ), 80.4 (d,
C
6,
F
C
4,
F
5 = 18.3,
(KBr): 3500, 3454, 3404, 3331, 3205, 3086, 3063, 1639, 1603, 1529,
1518, 1437, 1375, 1300, 1259, 1232, 1209, 1186, 1169, 1134, 874, 841,
3
4
C
4,
F
J
C
,
F
1
9
ꢃ1
ꢃ1 1
J
C
,
F
= 3.5 Hz, C|C ꢃꢃ H); F NMR (282.37 MHz, CDCl
3
d
820, 742, 717, 642, 511 cm
(300.13 MHz, acetone-d ):
(m, 2H, H , H ), 5.39 (br s, 2H, NH
(100.62 MHz, acetone-d ): = 164.0 (d,
= 12.2 Hz,
; nmax (Raman): 2214 (s) cm ; H NMR
5
7
3
(
1
ddd, 1F, J
F, J 2, 5 = 14.3, J
found 153.0383. C
F
5,
F
2 = 14.3, J
F
5,
3 = 11.0, J
N requires 153.0385.
H
6 = 10.1, J
F
5,
H
6
d= 7.20–7.11 (m, 2H, H , H ), 6.71–6.62
2
+
6
10
13
F
F
F
2,
H
F
2, 6 = 7.5 Hz, F ); HRMS (EI):
H
;
,
2 2
), 5.21 (br s, 2H, NH ); C NMR
1
10
8
H
5
F
2
6
d
J
C
10,
F
= 244.5 Hz, C ),
5 = 245.8,
J 1, 5 = 9.6 Hz, C ), 141.6 (dd,
3
12
1
1
51.2 (d,
J
C
12,
F
C
), 150.9 (dd,
J
C
5,
F
2
5
3
1
4.2.7.3. 4-Ethynyl-2,3,5,6-tetrafluoroaniline (4c). Preparative TLC
J
C
5,
4,
F
4 = 13.8 Hz, C ), 146.8 (d,
C F
(
Merck precoated plates, hexane/ethyl acetate, 7:1, twice) was used
1J
C
C
1
F
4 = 234.1,
2
C
J 4,
F
5 = 13.6 Hz, C ), 133.8 (d,
4
3
J
6,
C
14,
F
10 = 10.7 Hz,
5 = 23.0 Hz C ),
4
), 119.5 (d, 2J
4 = 18.9 Hz, C ), 103.3 (d, 2J
3
6
to isolate the title product (516 mg, 91%) as brown solid; m.p.
C
3,
F
C
F
ꢅ
2
9
3
4
50.1 C (decomp.); R
f
0.37;
n
max (KBr): 3483, 3385, 3302, 3198,
103.2 (d, J
C ), 102.0 (d,
C
9,
F
10 ꢆ14 Hz C ), 102.9 (dd, J
C
2,
F
4 = 7.5, J
C
2,
F
5 = 2.6 Hz
2
4
13
2
2932, 2120, 1665, 1622, 1504, 1433, 1364, 1310, 1250, 1173, 1146,
J
C
13,
7, 10 = 1.1 Hz C |C ), 88.2 (d, J
NMR (282.37 MHz, acetone-d ):
8 = 13.8, J 11, 10 = 11.0, J 11,
7 = 6.4 Hz, F ), ꢃ135.2 (ddd, 1F,
4 = 22.5, J 5, 6 = 12.6, J 5,
3 = 8.8 Hz, F ), ꢃ140.3 (ddd, 1F,
11 = 13.8, J 7 = 11.5, J 8,
5 = 22.5, J 3 = 11.1, J 4, 6 = 7.4 Hz, F ); HRMS (EI):
requires 280.0618.
F
10 = 21.1 Hz, C ), 100.2 (d,
J
C
11,
10 = 1.3 Hz, C |C );
= ꢃ114.8 (ddd, 1F,
11
F
10 = 25.6 Hz,
ꢃ1
1
11
7
8
7
8
1113, 953, 935, 802, 689, 627 cm ; H NMR (400.13 MHz, Acetone-
C
), 90.5 (d, J
C
F
C F
8,
1
3
19
d
6
): 5.87 (br s, 2H, NH
): = 147.8 (dm,
2 = 237.4,
3 = 4.3 Hz, C ), 87.6 (t, 2J
= 3.2 Hz, C|C ꢃꢃ H), 69.3 (t, J
282.37 MHz, Acetone-d ):
= ꢃ140.6 (dm, 2F, J
2,
3 ꢆ 22 Hz, F ); HRMS (EI):
N requires 189.0196.
2
), 4.10 (s,1H, C|C ꢃꢃ H); C NMR (100.62 MHz,
F
6
d
1
3
Acetone-d
6
d
J
C
3,
3 = 15.3 Hz, C ), 129.9 (tt,
4,
F
3 = 244.5 Hz, C ), 136.8 (ddm,
J
J
J
J
F
F
F
F
11,
F
F
H
F
H
1
2
2
2
4
5
J
C
2,
F
J
C
2,
F
J
C
1,
F
2 = 14.2,
5,
8,
4,
F
F
F
F
H
F
H
3J
1,
F
1
3 = 18.5 Hz, C ), 87.5 (t,
8,
10 = 7.7 Hz, F ), ꢃ153.3 (ddd, 1F,
8
C
C
F
F
H
F
H
1
9
4 +
J
C
,
F
,
C F
= 3.8 Hz, C|C ꢃꢃ H);
3,
2 ꢆ 22 Hz, F ),
, found 189.0192.
F NMR
F
4,
H
F
H
; , found
3
(
6
d
F
+
F
8 4 2
280.0617. C14H F N
2
ꢃ163.5 (dm, 2F, J
F
F
;
C
8
H
3
F
4
4.2.8.3.
4-((2-Amino-4,5-difluorophenyl)ethynyl)-2,3,5,6-
tetrafluoroaniline (2ac). Preparative TLC (Merck precoated
4
.2.8. General procedure for synthesis of 2-aminotolans 2(a–d)(a–c)
Pd(PPh Cl (28 mg, 0.04 mmol), CuI (17 mg, 0.09 mmol) and
N (3 mL) were added to a stirred solution of 2-iodaniline 3
plates, hexane/ethyl acetate, 5:1) was used to isolate 2ac
ꢅ
3
)
2
2
(310 mg, 98%) as light brown solid; m.p. 163.0 C (decomp.); R
f
Et
3
6 6 2
0.42; [Found: C, 53.29; H, 2.27. C14H F N requires C, 53.18; H,
(
1 mmol) and ethynylaniline 4 (1.3 mmol) in MeCN (12 mL) at r.t. in
1.91%]; max (KBr): 3510, 3471, 3406, 3377, 3199, 3059, 2220 (ww),
1622, 1664, 1593, 1525, 1500, 1458, 1431, 1358, 1313, 1292, 1227,
n
ꢅ
an argon atmosphere. The reaction mixture was stirred at 60 C for
4
CH
(
(
ꢃ1
h and allowed to cool to r.t. Then, the mixture was diluted with
1192, 1161, 1103, 958, 935, 883, 845, 833, 742, 685, 633, 542 cm
;
ꢃ1
1
2
Cl
3 ꢄ 50 mL). The combined organic layers were washed with H
30 mL) and dried (MgSO
2
(10 mL), poured into H
2
O (40 mL) and extracted with CH
2
Cl
2
n
max (Raman): 2218 (s) cm ; H NMR (300.13 MHz, acetone-d
6
):
3
2
O
d
= 7.20 (dd, 1H, J
6, 5 = 12.7, J 6, 4 = 7.2 Hz, H ), 5.81 (br s, 2H, NH
NH NMR (100.62 MHz, acetone-d ):
H
3,
F
4 = 10.9, J
H
3,
F
5 = 8.8 Hz, H ), 6.72 (dd, 1H,
), 5.23 (br s, 2H,
= 151.6 (d,
C F
J 1, = 10.1 Hz, C ), 146.8 (dm,
6
4
). Evaporation of the solvent in vacuo
J
H
F
H
F
2
1
3
yielded crude product 2 and a small amount of 9 that were
separated and purified by preparative TLC.
2
);
C
6
d
1
5
3
1
J
C
5, = 247.5 Hz, C ), 147.3 (d,
F
1J
10,
= 248.8 Hz, C ), 141.7 (dd,
10
1
J
= 234.9,
2
C
4
F
C
F
C F
4, J 4, = 13.8 Hz,
= 15.4 Hz, C ), 129.5 (td,
1
2
11
4
(
.2.8.1.
2-[(4-Amino-2-fluorophenyl)ethynyl]-4,5-difluoroaniline
C ), 135.8 (dm,
J
C
11,
12, = 4.1 Hz,
= 2.0 Hz, C ), 102.2 (d,
F
= 237.6,
J
C
11,
F
2
= 14.4, 3J
12
2
2aa). Preparative TLC (Merck precoated plates, hexane/ethyl
J
J
J
C
C
C
C
12,
F
C
F
C
), 119.1 (dd,
C
J 3,
F
= 19.1,
3
3
3
2
6
acetate, 5:1 twice) was used to isolate 2aa (252 mg, 96%) as light
brown solid; m.p. 92.4 C (decomp.); R
3
3
1
1
3,
2,
9,
F
F
F
J 6, = 21.1 Hz, C ), 101.5 (dd,
C F
ꢅ
4
2
4
7
8
f
0.35; [Found: C, 64.02; H,
max (KBr): 3485,
400, 3377, 3219, 3053, 2974, 2927, 2854, 2200, 1699, 1626, 1562,
= 7.2,
J
C
2,
F
= 2.7 Hz C ), 92.9 (t,
J
C
7,
F
19
= 2.3 Hz C |C ), 88.7 (t,
F NMR (282.37 MHz,
(ddd, 1F,
2J
10 = 18.7 Hz, C ), 80.2 (s, C |C );
9
7
8
.25. C14
H
9
F
3
N
2
requires C, 64.12; H, 3.46%];
n
acetone-d
6
):
4 = 22.5, J
8 ꢆ 21 Hz,
5 = 22.5, J
d
= ꢃ133.9
5,
5
518, 1471, 1441, 1362, 1327, 1302, 1281, 1236, 1203, 1165, 1122,
J
J
J
J
F
F
F
F
5,
7,
4,
8,
F
F
5,
4,
H
H
6 = 12.7, J
F ),
F H
3 = 10.9, J 4,
F
H
3 = 8.8 Hz, F ), ꢃ140.2 (dm, 2F,
ꢃ1
3
1
7
066, 958, 887, 854, 820, 764, 741, 627, 488, 463 cm
;
H NMR
F
ꢃ152.9
(ddd,
1F,
7
4
(
300.13 MHz, acetone-d
6
):
4 = 7.3 Hz,
8 = 2.6 Hz,
8,
.28 (br s, 2H, NH
d
= 7.39–7.27 (m, 2H, H , H ), 6.71 (dd,
F
F
6 = 7.2 Hz, F ), ꢃ161.9 (dm, 2F,
6
8
+
1
H,
10,
8,
J
H
6,
11 = 11.5, J
7 ꢆ J 8, 11 ꢆ9, J
F
5 = 12.8, J
H
6,
F
H ),
6.55
6.37
(dd,
(td,
1H,
1H,
F
6 6 2
7 ꢆ21 Hz, F ); HRMS (EI): ; , found 316.0431. C14H F N
J
J
H
F
10,
H H
H10),
requires 316.0430.
8
H
H
H
F
H
H
10 = 2.6 Hz, H ), 5.46 (br s, 2H, NH
2
),
):
C F
J 12, = 12.2 Hz,
13
5
d
2
);
C
NMR (100.62 MHz, acetone-d
6
4.2.8.4. 2-((4-Amino-2-fluorophenyl)ethynyl)-3,4,6-trifluoroaniline
(2ba). Preparative TLC (Merck precoated plates, hexane/ethyl
acetate, 10:1 twice) was used to obtain 2ba (221 mg, 79%) as light
1
10
3
= 164.0 (d,
), 150.9 (dd,
J
C
10,
F
= 244.5 Hz, C ), 151.2 (d,
1
2
1
5 = 245.8, 2J
5
C
J
C
5,
F
C
5,
F
4 = 13.8 Hz, C ), 146.8 (d,
3
1
1
2
4
J
C
1,
33.8 (d,
03.3 (d, 2J
F
5 = 9.6 Hz, C ), 141.6 (dd, J
C
4,
F
4 = 234.1,
J
C
4,
3,
F
5 = 13.6 Hz, C ),
4 = 18.9 Hz, C ),
f
brown solid; (decomp. befor melt.); R 0.22; nmax (KBr): 3481, 3385,
3
10 = 10.7 Hz, C ), 119.5 (d, 2J
14
3
1
1
(
C
8
d
1
J
C
14,
6, 5 = 23.0 Hz C ), 103.2 (d,
4 = 7.5,
F
C
F
3227, 3067, 2205, 1618, 1591, 1562, 1501, 1385, 1335, 1310, 1219,
6
2
9
ꢃ1 1
C
F
J
C
9,
F
10 ꢆ14 Hz C ), 102.9
1173, 1119, 984, 957, 910, 839, 814, 745, 708, 692, 606, 532 cm ; H
3
4
2
4
dd,
J
C
2,
),100.2 (d, J
8.2 (d, J 8, 10 = 1.3 Hz, C |C ); F NMR (282.37 MHz, acetone-d
= ꢃ109.8 (dd, 1F, J
F, J 5, 4 = 22.5, J 5,
F
J
C
2,
F
5 = 2.6 Hz C ), 102.0 (d,
J
C
13,
10 = 1.1 Hz C |C ),
):
7 = 8.0 Hz, F ), ꢃ135.5 (ddd,
F
10 = 21.1 Hz,
NMR
(300.13 MHz,
acetone-d
H ),
6
):
d
= 7.32
(t,
1H,
1
3
2
11
7
8
7
C
11,
F
10 = 25.6 Hz, C ), 90.5 (d, J
7,
C F
J
J
H
7,
5,
H
8 ꢆ J
H
7,
F
= 8.2 Hz,
7.10
(td,
1H,
7
8
19
5
10
C
F
6
H
8
F
6 ꢆ J
H
5,
F
4 = 10.6, J
H
5,
F
3 = 7.3 Hz, H ), 6.57–6.50 (m, 2H, H ,
11
13
F
11,
H
10 = 11.5, J
5,
F
11,
3 = 8.8 Hz, F ), ꢃ153.1 (ddd, 1F,
H
H ), 5.47 (br s, 2H, NH
acetone-d ): = 164.0 (d,
= 11.8 Hz, C ), 146.4 (ddd,
2
), 5.08 (br s, 2H, NH ); C NMR (125.77 MHz,
2
5
1
10
F
F
F
H
6 = 12.8, J
F
H
6
d
J 10,
C F
= 246.9 Hz,
C
), 151.3 (d,
3, = 13.6 Hz,
3
12
1
= 243.0, 2J
C
J 12,
F
J
C
3,
F
C
F

L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
93
C ), 145.3 (dd, 1J
3
6,
= 237.0, 3
J
6,
= 10.9, 4
J
6,
= 3.2 Hz, C ), 140.4
6
J
J
J
3,
4,
8,
4 = 21.7, J
3 = 21.7, J
7 ꢆ19 Hz, F ); HRMS (EI):
3,
4,
6 = 13.4, J
5 = 10.5, J
3,
4,
5 = 7.3 Hz, F ), ꢃ151.7 (ddd, 1F,
3
C
F
C
3
F
C
F
F
F
F
F
F
F
F
F
F
H
1
2
4
4
(
dt,
J
C
4,
F
= 235.8,
C
J 4,
F
ꢆ J
C
4,
C
F
14
= 13.9 Hz, C ), 134.7 (d,
F
H
8
F
F
6 = 2.8 Hz, F ), ꢃ161.9 (dm, 2F,
2
1
), 110.4 (s, C13), 104.8 (t,
+
J
C
1,
5,
F
= 15.0 Hz, C ), 134.0 (s,
;
, found 334.0337. C14
H
5
F
7
N
2
2J
4 ꢆ J
2
5,
6 = 24.8 Hz, C ), 101.1 (d,
5
2
F
J
C
2,
= 24.1 Hz, C ), 99.3
2
requires 334.0336.
C
F
C
F
F
2
= 24.1 Hz, C ), 97.2 (d, 2
11
9
(
J
(
J
J
J
J
d,
8,
282.37 MHz,
11, 10 = 11.8, J
3 = 13.5, J 6,
J
C
11,
F
J
C
9,
= 16.2 Hz, C ), 96.2 (d,
7
8
7
8
19
C
F
= 3.4 Hz C |C ), 80.0 (m,
acetone-d ):
7 = 8.6 Hz,
5 = 11.1, J 6,
6 = 13.5, J 3,
5 = 10.5, J 4,
requires 280.0618.
J
7,
C F
= 2.6 Hz, C |C );
F
NMR
1F,
4.2.8.7.
2-((4-Amino-2-fluorophenyl)ethynyl)-3,4,5,6-
tetrafluoroaniline (2ca). Preparative TLC (Merck precoated
plates, hexane/ethyl acetate, 10:1 twice) was used to obtain 2ca
(241 mg, 81%) as light brown solid; m.p.112.5 C (decomp.); R
max (KBr): 3497, 3420, 3387, 3219, 3044, 3959, 2212, 1630, 1562,
1524, 1497, 1439, 1342, 1325, 1306, 1229, 1173, 1121, 984, 934, 839,
6
d
= ꢃ109.7
(dd,
(ddd,
11,
H
F11),
ꢃ136.0
1F,
F
H
F
6
ꢅ
F
F
F
6,
3,
4,
F
F
F
F
H
F
F
4 = 3.1 Hz, F ), ꢃ141.2 (ddd, 1F,
f
0.25;
3
4 = 21.8, J
3 = 21.8, J
F
3,
4,
F
F
H
5 = 7.3 Hz, F ), ꢃ151.9 (ddd, 1F,
n
4
+
F
H
F
F
6 = 3.1 Hz, F ); HRMS (EI): ; , found
ꢃ1
1
2
80.0613. C14
H
8
F
4
N
2
814, 745, 694, 625, 602, 532, 451 cm
acetone-d ): = 7.29 (t, 1H, J 7,
8 ꢆ J
2
(m, 2H, H , H ), 5.49 (br s, 2H, NH ), 5.41 (br s, 2H, NH ); C NMR
; H NMR (300.13 MHz,
7
6
d
H
H
H F
7, = 8.2 Hz, H ), 6.54–6.47
1
0
8
13
4
.2.8.5.
2-((4-Amino-2,5-difluorophenyl)ethynyl)-3,4,6-
2
1
10
trifluoroaniline (2bb). Preparative TLC (Merck precoated plates,
hexane/ethyl acetate, 5:1 twice) was used to obtain 2bb (253 mg,
(125.77 MHz, CDCl
3
12
):
d
= 164.0 (d, J
C
10,
F
= 249.7 Hz, C ), 149.5 (d,
= 247.5, J 3, = 11.2 Hz, C ),
C F
5, = 14.0, J 5, = 5.3 Hz, C ),136.3 (ddm,
F C F
= 13.3 Hz, C ), 134.0 (s, C ), 133.3 (dm,
3
1
2
3
J
C
12,
F
= 11.1 Hz, C ), 147.5 (ddd, J
C
3,
F
ꢅ
1
2
3
5
8
5
9
5%) as brown solid; m.p. 125.2 C (decomp.); R
f
0.44; [Found: C,
requires C, 56.39; H, 2.37; N,
max (KBr): 3496, 3479, 3449, 3394, 3353, 3100, 3075, 2213,
639,1610,1586,1529,1505,1438, 395,1366,1311,1289,1242,1219,
141.4 (dtd, J
C
5,
F
2
= 251.5, J
C
1
6
14
6.44; H, 2.61; N, 9.05. C14
H
7
F
5
N
2
J
J
J
C
C
C
C
6,
F
= 239.0,
ꢆ 14 Hz,
J
C
6,
F
2
2
1
1
.39%];
n
1,
4,
11,
F
C ),
132.9
(dtm,
13, = 2.2 Hz, C ), 101.6 (d,
9, = 16.1 Hz, C ), 95.4 (t,
= 16.6 Hz, C ), 79.8 (m, C |
):
ꢃ139.2
ꢃ158.3
ꢃ162.3
C F
J 4, = 244.2,
3
= 13.3 Hz, C ), 110.7 (d, 4J
4
13
1
1
F
ꢆ J
C
4,
F
C
F
ꢃ1
1
2J
11
), 99.9 (d, 2J
9
174, 1112, 982, 912, 873, 838, 747, 689, 545 cm
;
H NMR
1H,
F
= 24.4 Hz,
C
C
F
7
8
2
2
7
(
300.13 MHz,
7, 8 = 11.4, J
5, 5,
6 ꢆ J
10, 11 = 11.0, J
acetone-d
6
):
d
= 7.28
7.15
6.70
8 = 7.5 Hz, H ), 5.54 (br s, 2H, NH
); C NMR (100.62 MHz, acetone-d ):
(dd,
J
C
8,
F
= 3.2 Hz C |C ), 95.1 (dm,
J
C
2,
F
H7),
(td,
1H,
C );
8
19
F NMR (282.37 MHz, acetone-d
d
= ꢃ109.7 (dd, 1F,
J
J
J
H
F
H
7,
F
11 = 6.4 Hz,
6
4 = 10.7, J
10,
H
5,
F
3 = 7.3 Hz,
H5),
(dd,
), 5.17 (br
= 160.5 (d,
1H,
J
F
J
F
J
F
J
F
J
F
11,
H
10 = 11.7, J
4 = 22.2, J 3,
6 ꢆ J 5, 4 ꢆ 21 Hz,
5 = 19.9, J 6, 3 = 9.1, J
4, 4, 6 = 6.6 Hz, F ); HRMS (EI):
5 ꢆ 21, J
requires 298.0529.
F
11,
H
7 = 8.2 Hz,
F
11
),
(dd,
(t,
1F,
1F,
1F,
H
H
F
H
F
10
3
F
H
F
2
3,
5,
6,
4,
F
F
F
F
F
F
6 = 9.1 Hz,
F ),
1
3
5
s, 2H, NH
2
6
d
F
F
F ),
(m,
1
10
1
13
6
J
J
J
J
C
C
C
C
C
10,
F
= 244.2 Hz, C ), 147.3 (d, J
C
13, = 235.0 Hz, C ), 147.2 (ddd,
= 3.6 Hz, C ), 146.0 (ddd,
= 3.3 Hz, C ), 140.9 (dt,
F
F
F
F
6,
F
4 = 6.6 Hz, F ), ꢃ175.9 (tm, 1F,
1
1
1
2
4
3
4 +
3,
6,
4,
F
F
F
= 243.6,
J
C
3,
F
= 13.7,
J
C
3,
F
3 ꢆ J
F
F
F
F
; , found
3
4
6
= 237.2,
J
C
6,
F
= 10.8,
J
C
6,
F
7 5 2
298.0525. C14H F N
= 235.8, 2J
4,
ꢆ J
3
4,
C F
= 13.8 Hz, C ), 140.5 (dd,
4
2
J
12,
= 2.6 Hz, C ),
C
F
12
C
F
= 15.1,
3J
12,
= 12.0 Hz, C ), 135.5 (dm,
2
J
1,
= 3.4 Hz,
= 15.4, 3
J
C
1,
1
4.2.8.8.
2-((4-Amino-2,5-difluorophenyl)ethynyl)-3,4,5,6-
tetrafluoroaniline (2cb). Preparative TLC (Merck precoated
plates, hexane/ethyl acetate, 7:1 twice) was used to isolate 2cb
(234 mg, 74%) as brown solid; m.p. 94.5 C (decomp.); R 0.22; n
f max
(KBr): 3483, 3412, 3310, 3196, 2955, 2928, 2868, 2216, 1641, 1530,
1499, 1452, 1429, 1366, 1312, 1246, 1221, 1184, 1119, 1086, 986, 937,
F
C
F
C
F
2
3
14
1
19.0 (dd,
J
C
14,
F
= 22.2,
J
C
14,
F
), 105.9 (t,
2J
11, = 27.0,
2, = 7.1,
= 9.0 Hz, C ), 95.5
2
3
2
5
J
J
C
C
C
5,
11,
2,
F
4 ꢆ J
C
5,
F
6 = 23.7 Hz,
C ),
102.8
(dd,
C
3
F
11
), 100.0 (ddd, 2J
ꢅ
F
= 5.0 Hz,
= 1.7 Hz, C ), 97.3 (dd,
C
C
2,
F
= 17.4,
J
C
9
F
3J
2
2
J
= 18.8, 3
J
F
C
9,
F
C
9,
F
7
8
7
8
19
(
m, J
282.37 MHz,
11, 8 = 13.8, J
3 = 13.7, J 6,
11 = 13.8, J
7,
C F
= 2.2 Hz C |C ), 81.4 (m, J
acetone-d ):
10 = 11.0, J 11,
5 = 11.1, J 6,
4 = 2.9 Hz, F ), ꢃ140.2 (ddd, 1F,
7 = 11.4, J 8,
3,
5 = 7.3 Hz, F ), ꢃ151.7 (ddd, 1F,
4,
C
8,
F
= 2.2 Hz, C |C ); F NMR
ꢃ1
1
(
6
d
= ꢃ114.2 (ddd, 1F,
870, 841, 824, 691, 544, 482, 436 cm
acetone-d ): = 7.18 (dd, 1H, J 7, 8 = 11.5, J
(dd, 1H, J 10, 11 = 11.0, J 10, 8 = 7.5 Hz, H ), 5.44 (br s, 2H, NH
5.36 (br s, 2H, NH ); C NMR (100.62 MHz, acetone-d ): = 159.8
; H NMR (300.13 MHz,
11
7
J
J
J
J
J
F
F
F
11,
H
F
H
7 = 6.4 Hz, F ), ꢃ135.8 (ddd, 1F,
6
d
H
F
H
10
7,
F
11 = 6.4 Hz, H ), 6.63
),
6
F
F
F
F
6,
8,
3,
4,
F
F
F
F
F
H
F
F
H
F
H
F
2
8
13
F
8,
H
F
H
10 = 7.5 Hz, F ), ꢃ140.8 (ddd, 1F,
2
6
d
3
1
10
1
3
4 = 21.8, J
3 = 21.8, J
F
3,
4,
F
6 = 13.7, J
F
H
(d,
C F C F
J 10, = 243.8 Hz, C ), 147.2 (dm, J 3, = 241.0 Hz, C ), 146.5
4
+
1
13
1
2
F
H
5 = 10.5, J
F
F
6 = 2.9 Hz, F ); HRMS (EI):
requires 298.0524.
;
,
(dm,
C
J 13,
F
= 234.9 Hz, C ), 141.2 (dtd,
J
C
5,
F
3
= 248.5,
J
C
5,
F
= 14.2,
3
5
2
12
found 298.0526. C14
7
H F
5
N
2
J
C
5,
F
= 5.7 Hz, C ), 139.8 (dd,
J
C
12,
F
= 15.4,
J 12, = 12.3 Hz, C ),
C F
1
2
6
1
35.8 (ddm,
J
C
6,
F
= 238.5,
J 6, = 12.4 Hz, C ), 135.1 (dm,
C F
2
1
1
2
4
.2.8.6.
4-((2-Amino-3,5,6-trifluorophenyl)ethynyl)-2,3,5,6-
J
C
1,
4,
F
= 11.3 Hz, C ), 131.6 (dtm,
J
C
4,
F
= 239.6,
J
C
4,
F
= 14.7,
3J
= 3.4 Hz, C ), 118.2 (dd,
4
2
J
= 22.2,
3
J 14, = 3.0 Hz, C ),
14
tetrafluoroaniline (2bc). Preparative TLC (Merck precoated
plates, hexane/ethyl acetate, 5:1 twice) was used to isolate 2bc
C
F
C
14,
F
C F
2
3
11
2
101.9 (dd,
J
C
11,
F
9
= 27.1,
J
C
11,
F
= 5.3 Hz, C ), 96.3 (dd,
J
C
9,
= 16.9 Hz, C ),
= 2.0 Hz C |C ); F NMR (282.37 MHz, acetone-d ):
= ꢃ114.2 (ddd, 1F, 11, 8 = 13.7, J 11, 10 = 11.0, J 11, 7 = 6.5 Hz,
), ꢃ138.7 (ddd, 1F, J 3, 4 = 22.1, J 3, 6 = 9.1, J 3, 5 = 1.5 Hz, F ),
ꢃ140.2 (ddd, 1F, 8, 11 = 13.7, J 8, 7 = 11.5, J 8, 10 = 7.5 Hz, F ),
ꢃ157.4 (td, 1F, J 5, 6 ꢆ J 5, 4 ꢆ 21, J 5, 3 = 1.5 Hz, F ), ꢃ162.0 (m,
1F, 6, 5 = 19.8, J 6, 3 = 9.1, J 6,
4 = 6.6 Hz, F ), ꢃ175.4 (td, 1F,
4, 4, 5 ꢆ 21, J 4, 6 = 6.6 Hz, F ); HRMS (EI):
3 ꢆ J
316.0429. C14 requires 316.0430.
F
= 18.6,
ꢅ
3
7
8
2
2
(
[
157 mg, 47%) as light brown solid; m.p.135.1 C (decomp.); R
f
0.53;
requires C, 50.32; H,
max (KBr): 3491, 3452, 3385, 3203, 3064, 2968,
931, 2220, 1664, 1608, 1504, 1433, 1387, 1329, 1306, 1279, 1173,
J
C
9,
F C F
= 9.4 Hz, C ), 94.4 (m, C |C ), 93.8 (dm, J 2,
7
8
19
Found: C, 49.84; H, 1.76; N, 8.18. C14
H
5
F
7
N
2
79.2 (m, J
d
F
C
7,
F
6
1
.51; N, 8.38%];
n
J
F
F
F
H
F
H
11
3
2
1
F
F
F
F
F
F
ꢃ1
1
8
130, 1115, 1038, 939, 920, 843, 725, 694, 642, 617, 579 cm
NMR (300.13 MHz, acetone-d ): = 7.23 (td,
5, 5, 4 = 10.7, J 3 = 7.3 Hz, H ), 6.02 (br s, 2H, NH
6 ꢆ J
br s, 2H, NH
;
H
J
F
F
F
H
F
H
5
6
5
d
1H,
), 5.22
= 146.9 (dm,
F
F
F
F
F
F
6
J
H
F
H
F
H
5,
F
2
J
F
F
F
F
F
F
1
3
4
+
(
2
); C NMR (100.62 MHz, acetone-d
6
):
d
J
F
F
F
F
F
F
; , found
1
4
10
1
1
2
J
J
C
C
C
10,
F
= 251.2 Hz,
C
), 146.4 (ddd,
J
J
C
3,
6,
F
= 244.7,
J
C
3,
F
= 14.0,
= 11.1,
= 13.0 Hz,
6 6 2
H F N
3
3
3,
6,
F
= 3.6 Hz, C ), 145.2 (ddd,
C
F
= 237.1,
C F
J 6,
4J
= 3.5 Hz, C ), 140.0 (dt, 1J
6
4,
= 235.6, 2J
4,
ꢆ J
3
4.2.8.9.
2-((4-Amino-2,3,5,6-tetrafluorophenyl)ethynyl)-3,4,5,6-
tetrafluoroaniline (2cc). Preparative TLC (Merck precoated
plates, hexane/ethyl acetate, 4:1 twice) was used to obtain 2cc
(169 mg, 48%) as white solid; m.p. 151.3 C (decomp.); R
(KBr): 3510, 3416, 3397, 3202, 2926, 2230, 1665, 1609, 1530, 1504,
1460,1337,1321,1306,1169,1115,1013, 972, 939, 746, 692, 573, 523,
F
C
F
C
F
C
4,
F
4
1
2
11
C ), 135.9 (dm,
J
C
11,
F
= 237.2,
J
C
11,
F
= 14.7 Hz, C ), 135.1 (dm,
2
3
1
2
J
C
1,
F
= 15.3,
J
C
1,
F
= 2.4 Hz, C ), 130.4 (td,
J
C
12,
F
= 14.7,
3J
12,
= 4.7 Hz, C ), 106.0 (t,
12
2
J
C
5,
4 ꢆ J
2
6 = 23.7 Hz, C ), 98.1
5
ꢅ
0.53;
n
max
C
F
F
C
5,
F
f
2
3
3
2
(
ddd,
C
J 2,
F
= 17.7,
J
C
2,
F
= 7.0,
J
C
2,
F
= 1.6 Hz, C ), 87.9 (t,
2
9
7
8
J
C
9,
8,
= ꢃ135.5 (ddd, 1F, J
ꢃ139.8 (dm, 2F,
F
= 18.0 Hz, C ), 86.6 (m,
= 2.7 Hz, C |C );
J
7,
C F
= 4.0 Hz C |C ), 86.1 (m,
):
7
8
19
ꢃ1
1
J
C
F
F
NMR (282.37 MHz, acetone-d
6
453 cm
NH ), 5.52 (br s, 2H, NH
= 148.2 (ddt, J
;
H NMR (300.13 MHz, acetone-d
6
):
d
= 6.00 (br s, 2H,
):
3, = 3.9 Hz, C ),
C F
6
13
d
F
6,
7,
F
3 = 13.6, J
F
6,
H
5 = 11.0, J
F
6,
F
4 = 2.8 Hz, F ),
8 ꢆ 19 Hz, F ), ꢃ140.5 (ddd, 1F,
2
2
); C NMR (100.62 MHz, acetone-d
6
3
7
1
2
3
4
J
F
F
d
C
3,
F
= 245.5, J
C
3,
F
= 11.1, J
C
3,
F
ꢆ J

9
4
L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
6
+
1
J
48.1 (dm, 1J
C
10,
5, = 5.3 Hz, C ), 136.8 (dm, J
C , C ), 136.3 (dm,
F
= 244.6 Hz, C10), 142.8 (dtd, 1J
C
5,
ꢆ 235 Hz,
4, = 235.6,
F
= 249.6,
J
F
6,
F
5 = 19.6, J
F F
6, 3 = 10.4 Hz, F ); HRMS (EI): ; , found 366.0395.
2
= 13.9, 3J
5
1
1
C
5,
F
11
C
F
C
11,
F
ꢆ J
C
6,
J
F
C H F N requires 366.0400.
15 6 8 2
6
2
1
1
J 1,
C F
= 11.6 Hz, C ), 132.5 (dtm,
C
F
2
4
2
3
12
J
C
4,
F
2
= 13.6 Hz, C ),131.2 (m, J
C
12,
F
= 10.1, J
9, = 18.1 Hz, C ), 87.3 (m, C |C ),
5.8 (m, C |C ); F NMR (282.37 MHz, acetone-d ):
= ꢃ138.4
5 = 2.4 Hz, F ), ꢃ139.8 (dm, 2F,
5, 5, 5, 3 = 2.4 Hz,
6,
ꢃ175.4
C
12,
F
= 4.3 Hz, C ), 93.8
4.2.8.12.
2-((4-Amino-2,3,5,6-tetrafluorophenyl)ethynyl)-3,5,6-
trifluoro-4-(trifluoromethyl)aniline (2dc). By preparative TLC
(Merck precoated plates, hexane/ethyl acetate, 5:1 twice), we
obtained 2dc (145 mg, 36%) as light brown solid; m.p. 131.0 C
2
2
9
7
8
(
dm, J
C
2,
F
= 14.8 Hz, C ), 88.8 (t, J
C
F
7
8
19
8
6
d
3
ꢅ
(
ddd, 1F, J
F
3,
F
4 = 21.9, J
F
3,
F
6 = 9.2, J
F
3,
F
7
J
F
7,
F
8 ꢆ 19 Hz, F ), ꢃ156.3 (td, 1F, J
F
F
6 ꢆ J
F
F
4 ꢆ 20, J
F
F
(decomp.); R
requires C, 44.79; H, 1.00; N, 6.97%];
2928, 2642, 2222, 1662, 1606, 1527, 1506, 1446, 1346, 1306, 1244,
f
0.44; [Found: C, 44.56; H, 1.14; N, 6.90. C15
4 10 2
H F N
5
6
F ), ꢃ161.8 (m, 1F, J
dm, 2F,
4, 4,
5 ꢆ 21, J
52.0245. C14
F
6,
F
5 = 19.7, J
F
6,
F
3 = 9.3, J
F
F
4 = 6.5 Hz, F ), ꢃ161.9
n
max (KBr): 3514, 3408, 3199,
8
(
J
F
8,
F
7 ꢆ19 Hz,
F )
(td,
,
1F,
found
4
+
ꢃ1
1
J
F
F
3 ꢆ J
F
F
F
4,
F
6 = 6.5 Hz, F ); HRMS (EI):
;
1180, 1128, 993, 937, 903, 750, 708, 550, 451 cm
(300.13 MHz, acetone-d ): = 6.36 (br s, 2H, NH ), 5.98 (br s, 2H,
): = 157.0 (dm,
= 7.2 Hz, C ), 149.1 (dm,
;
H NMR
3
H
4
F
8
N
2
requires 352.0241.
6
d
2
13
NH
2
);
C
NMR (125.77 MHz, acetone-d
6
d
1
3
5
3
1
4.2.8.10.
2-((4-Amino-2-fluorophenyl)ethynyl)-3,5,6-trifluoro-4-
J
C
3,
5,
F
= 254.6,
J
C
3,
F
J
C
5,
F
= 256.5,
2J
= 9.1 Hz, C ), 147.8 (dm, J
1
10,
= 246.5, 2J
= 10.6 Hz, C ),
10
(
trifluoromethyl)aniline (2da). Preparative TLC (Merck precoated
plates, hexane/ethyl acetate, 10:1 twice) was used to obtain 2da
C
F
C
F
C
10,
F
2
1
1
144.1 (m,
J
C
1,
F
11
= 12.1 Hz, C ), 136.8 (dm,
J
C
11,
F
= 237.8,
ꢅ
2
1
= 237.7, 2
6
(
[
2
2
278 mg, 80%) as light brown solid; m.p.145.1 C (decomp.); R
Found: C, 51.94; H, 2.29; N, 7.63. C15 requires C, 51.74; H,
max (KBr): 3510, 3491, 3402, 3221, 2957, 2926,
858, 2212, 1643, 1628, 1562, 1522, 1503, 1408, 1354, 1329, 1279,
242, 1213, 1175, 1117, 930, 874, 845, 814, 743, 692, 667, 629, 606,
f
0.69;
C
J 11,
F
= 15.1 Hz, C ), 136.3 (ddd, J
C
6,
= 4.3 Hz,
F
J
C
6,
F
= 15.0 Hz, C ),
2
3
12
H
7
F
7
N
2
130.3 (tt,
J
C
12,
F
= 14.2,
J
C
12,
F
C
), 124.6 (q,
1
2
2
.03; N, 8.04%];
n
J
J
CF3
,
F
= 271.9 Hz, CF
3
), 95.3 (m,
= 12.9 Hz, C ), 94.6 (dm,
= 18.4 Hz, C ), 87.4 (m, C |C ), 85.3 (m, C |C ); F NMR
J
C
4,
F
= 34.6,
C F
J 4, = 16.6,
2
4
2
2
C
4,
9,
F
F
J 2, = 21.9 Hz, C ), 88.7 (t,
C F
2J
9
7
8
7
8
19
1
C
ꢃ1
1
5
1
2
11, 494, 451 cm ; H NMR (300.13 MHz, acetone-d
6
):
d
= 7.29 (t,
(282.37 MHz, acetone-d
CF 3,CF3 = 21.8, J
), ꢃ113.3 (qd, 1F, J
5, CF3 ꢆ J 5,
ꢃ161.9 (dm, 2F,
6, 5 = 19.4, J 6, 3 = 10.7 Hz, F ); HRMS (EI):
6
):
d
= ꢃ53.7 (t, 3F, JCF3
,
F
3 ꢆ JCF3
F
, 5 = 21.3 Hz,
7
10
8
3
H, J
H, NH
= 163.6 (d,
H
7,
H
8 ꢆ J
H
7,
F
= 8.2 Hz, H ), 6.53–6.48 (m, 2H, H , H ), 6.23 (br s,
3
F
F
3,
F
6 = 10.7 Hz, F ), ꢃ137.3 (m, 1F,
13
5
7
2
), 5.46 (br s, 2H, NH
2
); C NMR (125.77 MHz, CDCl
3
):
J
F
F
F
6 ꢆ 20 Hz, F ), ꢃ139.6 (dm, 2F, J
F
7,
F
8 ꢆ 19 Hz, F ),
1
= 247.0 Hz, C10), 155.4 (dm,
1
8
d
J
C
10,
F
J
C
3,
F
= 253.2,
F F
J 8,
7 ꢆ20 Hz, F ), ꢃ162.9 (dd, 1F,
3
= 6.8 Hz, C ), 151.9 (d, 3J
3
12
6
+
J
C
3,
5,
F
C
12,
F
= 11.7 Hz, C ), 147.6 (dm,
J
C
F
F
F
F
;
, found 402.0207.
1J
= 255.1,
2
J
5,
= 15.2 Hz, C ), 142.4 (d,
5
2
J 1,
C F
ꢆ 12 Hz, C ),
1
requires 402.0209.
C
F
C
F
15
H
4
10
F N
2
1
2
4
6
1
35.1 (ddd, J
C
6,
F
= 237.5,
J
C
6,
F
= 15.0,
J
C
6,
F
= 3.5 Hz, C ), 133.7 (d,
3
4
14
13
1
0
J
J
C
C
C
14,
13,
F
= 3.1 Hz, C ), 122.0 (q,
= 2.0 Hz,
J
CF3
,
F
= 271.3 Hz, CF
3
), 109.9 (d,
), 96.6 (d,
4.2.8.13.
4,4 -(Buta-1,3-diyne-1,4-diyl)bis(3-fluoroaniline)
(9a). Preparative TLC (Merck precoated plates, hexane/ethyl
acetate, 5:3) was used to isolate 9a (10 mg, 7%) as light brown
2
8
11
F
C
), 99.8 (d,
J
C
11,
F
= 24.1 Hz,
C
2J
9,
= 16.2 Hz, C ), 95.6 (m, C |C ), 94.9 (dm,
9
7
2
J
C
2,
= 21.6 Hz, C ),
2
F
F
2
2
= 16.5, 2
4
7
94.0 (m,
J
C
4,
NMR (282.37 MHz, CDCl
5 = 21.5 Hz, CF ),
ꢃ110.6
10 = 10.9, J 11, 7 = 7.8 Hz,
F11),
ꢃ114.7
3,CF3 = 21.6, J 3, 6 = 11.2 Hz, (dq,
ꢃ138.3
5, ꢃ165.2 (dd,
6 ꢆ 21 Hz,
5 = 20.2, J 6, , found 348.0492.
F
= 34.2, J
C
4,
F
C
J 4,
F
= 12.7 Hz, C ), 77.9 (m, C |
solid; (decomp. befor melt.); R
f
0.58; nmax (KBr): 3444, 3329, 3209,
8
19
C );
F
3
):
d
= ꢃ56.3 (t, 3F,
2956, 2926, 2854, 2145, 1616, 1566, 1502, 1452, 1323, 1246, 1209,
ꢃ1
1
J
J
J
CF3
,
F
3 ꢆ JCF3
,
F
3
(dd,
(dq,
1F,
1F,
1F,
1163, 1128, 1093, 958, 839, 816, 741, 685, 600, 469, 428 cm ; H
NMR (400.13 MHz, acetone-d ): = 7.23 (t, 2H,
5, 6 ꢆ 8 Hz, H ), 6.50–6.43 (m, 4H, H , H ), 5.55 (br s,
ꢆ J
4H, NH
F
F
11,
H
F
H
6
d
3
5
2
6
F
F
F ),
J
F
5,
J
H
F
H
5,
);
H
5
13
CF3 ꢆ J
F
F
F ),
1F,
2
6
C NMR (125.77 MHz, acetone-d ): d= 165.9 (d,
6
+
1
= 247.4 Hz, C3), 153.0 (d,
3
1
J
F
6,
F
F
F
3 = 11.2 Hz, F ); HRMS (EI):
;
C
J 3,
C
J 5,
C
2,
F
F
F
C F
J = 11.7 Hz, C ), 135.6 (d,
1,
6,
= 16.2 Hz, C ), 77.3 (s, C |C ),
= 2.2 Hz, C |C ); F NMR (282.37 MHz, acetone-d ):
3
= 3.0 Hz, C ), 111.1 (d, 4J
5
6
C
15
7
H F
7
N
2
requires 348.0489.
C
F
= 1.9 Hz, C ), 101.0 (d,
2J
2
2
4
7
8
C F
= 23.5 Hz, C ), 97.2 (d, J 4,
3
7
8
19
4.2.8.11. 2-((4-Amino-2,5-difluorophenyl)ethynyl)-3,5,6-trifluoro-4-
77.0 (d,
d
J 7,
C F
6
+
(trifluoromethyl)aniline (2db). By preparative TLC (Merck
= ꢃ109.2 (dd, 2F, J
,
F H
2 = 9.4, J
F H
, 5 = 8.0 Hz, F); HRMS (EI): ; ,
precoated plates, hexane/ethyl acetate, 5:1 three times), we
isolated 2db (234 mg, 64%) as light brown solid; m.p. 203.4 C
found 268.0812. C16H F N requires 268.0807.
10 2 2
ꢅ
0
(
decomp.); R
f
0.28;
nmax (KBr): 3514, 3485, 3402, 2928, 2857, 2216,
4.2.8.14.
4,4 -(Buta-1,3-diyne-1,4-diyl)bis(2,5-difluoroaniline)
1
641, 1612, 1530, 1503, 1489, 1443, 1408, 1371, 1331, 1308, 1259,
(9b). By preparative TLC (Merck precoated plates, hexane/ethyl
acetate, 5:1, three times), we isolated 9b (8 mg, 5%) as light brown
ꢃ1
1
H
215, 1180, 1132, 1080, 932, 881, 845, 816, 746, 660, 517, 438 cm
;
1
NMR (300.13 MHz, acetone-d
6
):
d
6.67
= 7.26 (dd, 1H,
solid; (decomp. befor melt.); R
f
0.14; nmax (KBr):3507, 3406, 2143,
7
J
J
H
7,
10,
F
8 = 11.5, J
11 = 11.0, J
H
7,
F
11 = 6.3 Hz,
10,
H ),
(dd,
1H,
1639, 1574, 1526, 1441, 1362, 1310, 1242, 1215, 1169, 872, 839, 743,
8 = 7.5 Hz, H1 ), 6.37 (br s, 2H, NH
0
), 5.55 (br
671, cm
ꢃ1
;
1
H NMR (400.13 MHz, acetone-d
):
d
= 7.16 (dd, 2H,
(dd, 2H,
); C NMR
H
F
H
F
2
6
1
3
3
s, 2H, NH
2
); C NMR (100.62 MHz, acetone-d
6
):
d
= 159.5 (d,
J
J
H
3,
6,
F
2 = 11.4, J
5 = 11.1, J
(100.62 MHz, acetone-d
H
3,
6,
F
5 = 6.5 Hz,
2 = 7.5 Hz, H ), 5.63 (br s, 4H, NH
H ),
6.62
1
10
1
3
6
13
J
C
10,
F
= 244.4 Hz, C ), 155.5 (dm, J
C
3,
F
= 253.8 Hz, C ), 147.4 (dm,
H
F
H
F
2
1J
= 255.2, J
2
5,
= 13.1 Hz, C ), 146.1 (dm, J
5
1
13,
ꢆ 12 Hz, C ), 139.4 (dd,
= 234.8 Hz, C ),
13
):
d
= 161.2 (d, J
1
5,
5 = 244.7 Hz, C ), 146.4
5
C
5,
F
C
2
F
C
F
6
C
F
1
2
1
2
2
3
1
1
J
42.5 (m,
J
C
1,
F
12
C
J 12,
F
= 15.6,
(d, J
C
2,
F
2 = 235.5 Hz, C ), 140.3 (t, J
C
1,
F
2 ꢆ J
6, 5 = 26.8 Hz, C ), 95.4 (dd,
2 = 8.5 Hz, C ), 76.3 (s, C |C ), 75.7 (s, C |C );
(282.37 MHz, acetone-d ): (dm,
= ꢃ113.8
5,
3 = 6.5 Hz, F ), ꢃ139.9 (m, 2F,
2,
C
1,
F
5 ꢆ14 Hz, C ), 118.8
3
1
= 237.8, 2
2
3
2
6
C
12,
F
= 12.3 Hz, C ), 135.0 (ddm,
J
C
6,
F
J
C
6,
F
= 15.4 Hz,
(d,
J
C
3,
F
2 = 21.5 Hz, C ), 101.9 (d,
J
C
F
6
1
2
2
3
4
7
8
7
8
19
C ), 121.7 (q,
J
CF3
,
F
= 271.2 Hz, CF
3
4
), 117.8 (dd,
J
J
C
14,
11,
F
F
= 22.3,
= 26.9,
J
C
4,
F
5 = 19.3, J
C
4,
F
F
3
14), 103.4 (m, C ), 101.5 (dd,
2
J
C
14,
F
= 3.3 Hz,
C
C
NMR
6
d
2F,
3J
= 4.8 Hz, C ), 95.9 (dd,
11
2
J
C
9,
= 19.0, 3
J
9,
ꢆ 20 Hz, C ), 94.0 (m, C |C ), 78.4 (m, J
NMR (282.37 MHz, acetone-d ):
5 = 21.4 Hz, CF ),
ꢃ114.0
3,CF3 = 21.6, J 3, 6 = 10.4 Hz,
ꢃ114.3
11, 10 = 11.0, J
6 ꢆ 21 Hz,
7 = 11.5, J 8,
= 9.0 Hz, C ), 94.2
9
J
J
5,
2,
2 = 13.4, J
5 = 13.4, J
5,
2,
6 = 11.1, J
3 = 11.4, J
5
C
11,
F
F
7
C
F
F
F
F
H
F
H
2
2
8
7
2
+
(
dm,
J
C
2,
F
F
C
7,
F
= 2.0 Hz C |
F
F
F
H
F
H
6 = 7.5 Hz, F ); HRMS (EI):
requires 304.0618.
; ,
8
19
C );
6
d
= ꢃ53.6 (t, 3F,
found 304.0612. C16
8
H F
4
N
2
J
J
J
J
J
CF3
,
F
3 ꢆ JCF3
,
F
3
(dq,
1F,
1F,
3
0
F
F
F
F
F
F
F ),
(ddd,
4.2.8.15. 4,4 -(Buta-1,3-diyne-1,4-diyl)bis(2,3,5,6-tetrafluoroaniline)
(9c). Preparative TLC (Merck precoated plates, hexane/ethyl
11
11,
5,
F
8 = 13.7, J
F
H
F
11,
H
7 = 6.3 Hz, F ), ꢃ138.5 (dq, 1F,
5
CF3 ꢆ J
F
5,
8,
F
F ),
ꢃ140.4
(ddd,
1F,
acetate, 4:1, twice) was used to obtain 9c (13 mg, 7%) as light
8
ꢅ
8,
F
11 = 13.7, J
F
H
F
H
10 = 7.5 Hz, F ), ꢃ163.3 (dd, 1F,
brown solid; m.p. 280.7 C (decomp.); R
f
0.44;
n
max (KBr): 3518,
3
470, 3416, 3192, 2924, 2648, 2559, 2153, 1661, 1626, 1603, 1508,

L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
95
ꢃ1
1
423, 1306, 1163, 1113, 957, 937 cm ; 1H NMR (300.13 MHz,
5:1, three times) to obtain 1ab (88 mg, 63%) as light brown solid; m.
13
ꢅ
Acetone-d
6
): 5.95 (br s, 4H, NH
2
); C NMR (100.62 MHz, Acetone-
3 = 244.7 Hz, C ),136.8 (ddm, J
p. 156.3 C (decomp.); R
f
0.58; [Found: C, 60.27; H, 3.08; N, 10.00.
1
3
1
d
6
): = 147.0 (dm, J
d
C
3,
F
C
2,
F
2 = 237.7,
C
14
8
H F
4
N
2
requires C, 60.01; H, 2.88; N, 10.00%]; max (KBr): 3475,
n
2
2
2
3
1
J
C
2,
F
3 = 14.7 Hz, C ),130.1 (tt, J
C
1,
3 = 18.2 Hz, C ), 83.4 (m, J
282.37 MHz, Acetone-d ):
= ꢃ140.1 (dm, 4F, J
2,
3 ꢆ 22 Hz, F ); HRMS (EI):
requires 376.0241.
F
2 = 14.4, J
= 3 Hz, C |C );
3,
2 ꢆ 22 Hz, F ),
, found 376.0240.
C
1,
F
3 = 4.2 Hz, C ), 88.1
3414, 3217, 3072, 2956, 2928, 2856, 1703, 1647, 1601, 1560, 1516,
1473, 1439, 1398, 1369, 1335, 1308, 1279, 1219, 1178, 1113, 928, 872,
2
4
7
8
19
(
(
t,
J
C
4,
F
C
,
F
F NMR
3
ꢃ1 1
6
d
F
+
F
854, 802, 783, 744, 629, 602, 494, 465 cm ; H NMR (300.13 MHz,
acetone-d ): = 10.61 (br s, 1H, NH), 7.49 (dd, 1H,
11 = 12.3, J
5 = 11.2, J 4,
6 = 11.0, J 7,
9,
8 ꢆ 13, J
2
ꢃ161.9 (dm, 4F, J
F
F
;
6
d
1
2
C
16
H
4
F
8
N
2
J
J
J
H
H
H
12,
4,
7,
F
H
12,
6 = 8.0 Hz,
F
8 = 7.1 Hz,
H
),
7.42
7.32
3,
11 = 7.6 Hz, H ), 5.26 (br s, 2H, NH
(dd,
(dd,
ꢆ 2 Hz, H ), 6.74
1H,
1H,
H4),
F
H
F
7
3
4
.2.9. General procedure for synthesis of 2-arylindoles 1(a–c)(a–d)
Method A. To a solution of 3 (0.5 mmol) in ethanol (25 mL), p-
TSA (190 mg, 1 mmol) was added, and the mixture was heated at
reflux with stirring. The mixture was allowed to cool to r.t., diluted
F
H
F
5 = 7.0 Hz, H ), 6.79 (m, 1H, J
H
F
9
13
(dd, 1H, J
H
F
H
9,
F
2
);
9 = 241.9,
9 = 1.5 Hz,
5 = 15.9 Hz, C ), 146.2 (dd,
C
1
NMR (100.62 MHz, acetone-d
6
):
d
12,
= 156.2 (dd,
J
C
9,
F
4
9
1
12 = 233.8, 4J
J
C
9,
F
12 = 1.3 Hz, C ), 147.6 (dd,
J
C
F
C
12,
F
1
2
1
2
6
with CH
CH Cl
(3 ꢄ 50 mL). The combined organic layers were washed
with H O (40 mL) and dried (MgSO ). The solvent was evaporated
2
Cl
2
(10 mL), poured into H
2
O (40 mL) and extracted with
C
), 147.4 (dd,
J
C
6,
F
6 = 237.8,
J
C
5
6,
F
1
5 = 234.9, 2J
2
2
2
J
5,
C F
C
5,
F
6 = 14.9 Hz, C ), 137.5 (dd,
J
C
11,
7a, 6 = 10.7 Hz,
13, 12 = 22.6,
C F
8, 12 = 7.2 Hz, C ),
F
12 = 15.3,
3J
11,
9 = 12.6 Hz, C ), 134.4 (s, C ), 132.0 (d, 3J
11
2
2
4
C
F
C
F
7
a
3
3a
2
in vacuo to obtain compound 1, which was then purified by
C
), 124.4 (d,
13,
106.2 (d,
J
C
3a,
F
5 = 8.5 Hz, C ), 113.1 (dd,
J
C
F
3
13
2
3
8
preparative TLC.
J
C
F
9 = 6.2 Hz, C ), 107.3 (dd, J
C
8,
F
9 = 15.1, J
2
4
2
Method B. To a solution of 3 (0.5 mmol) in MeCN (20 mL), PdCl
24 mg, 0.1 mmol) was added, and the mixture was heated at reflux
with stirring in an argon atmosphere. The mixture was allowed to
cool to r.t., diluted with CH Cl (10 mL), filtered, concentrated in
vacuo and applied to Merck precoated plates to purify 1 by
preparative TLC.
2
J
C
4,
F
5 = 19.1 Hz, C ), 103.1 (dd,
J
C
10,
F
9 = 28.6,
= 4.3 Hz, C ), 98.9 (d,
NMR (282.37 MHz, acetone-d ):
12 = 7.1 Hz, F ), ꢃ140.2 (ddd, 1F,
3
10
4
3
(
J
2J
d
C
10,
7, 6 = 21.8 Hz, C );
8,
9 = 7.6 Hz,
F
12 = 4.8 Hz, C ), 100.4 (m,
C F
J 3,
7
19
C
F
F
6
8
2
2
= ꢃ119.4 (m, 1F, J
F
H
9 ꢆ14, J
F H
8,
1
1
J
F
J
F
J
F
11, 12 = 12.3, J 11,
H
F
H
F
),
ꢃ144.9
(ddd,
1F,
6
6,
5,
F
5 = 20.5, J
6 = 20.5, J
F
6,
5,
H
H
7 = 11.0, J
4 = 11.2, J
F
6,
5,
H
4 = 8.0 Hz, F ), ꢃ148.4 (ddd, 1F,
5
+
Method C. To a solution of 3 (0.5 mmol) in MeCN (25 mL), KOH
F
F
F
H
7 = 7.0 Hz, F ); HRMS (EI): ; ,
(
84 mg,1.5 mmol) was added, and the mixture was heated at reflux
with stirring for 6 h. The mixture was allowed to cool to r.t., diluted
with CH Cl (10 mL), poured into H O (40 mL) and extracted with
CH Cl
(3 ꢄ 50 mL). The combined organic layers were washed
with H O (40 mL) and dried (MgSO ). The solvent was evaporated
found 280.0616. C14
8
H F
4
N
2
requires 280.0618.
2
2
2
4.2.9.3.
4-(5,6-Difluoro-1H-indol-2-yl)-2,3,5,6-tetrafluoroaniline
2
2
(1ac). The above-mentioned general procedure (Method B) was
followed, and the crude product was purified by preparative TLC
(Merck precoated plates, hexane/ethyl acetate, 5:1, three times) to
2
4
in vacuo to obtain compound 1, which was then purified by
ꢅ
preparative TLC.
obtain 1ac (106 mg, 67%) as brown solid; m.p. 218.7 C (decomp.);
f
R 0.60; nmax (KBr): 3485, 3385, 3205, 3070, 2962, 2926, 2854,1666,
4
.2.9.1. 4-(5,6-Difluoro-1H-indol-2-yl)-3-fluoroaniline (1aa). The
1639, 1614, 1549, 1502, 1473, 1396, 1344, 1302, 1263, 1207, 1174,
1119, 1078, 1034, 978, 935, 864, 843, 798, 741, 675, 631, 617, 525,
above-mentioned general procedure (Method A) was followed,
and the crude product was purified by preparative TLC (Merck
precoated plates, hexane/ethyl acetate, 5:1, four times) to obtain
ꢃ1
1
467, 446 cm ; H NMR (300.13 MHz, acetone-d
1H, NH), 7.49 (dd, 1H, J 4, 5 = 11.1, J 4, 6 = 8.0 Hz, H ), 7.39 (dd, 1H,
7, 6 = 11.0, J 7, 5 = 7.0 Hz, H ), 6.85 (m, 1H, J
(br s, 2H, NH
6
): d= 10.67 (br s,
4
H
F
H
F
ꢅ
7
3
1
0
3
1
1
aa (59 mg, 45%) as light brown solid; m.p. 176.3 C (decomp.); R
f
J
H
F
H
F
H
3,
F
ꢆ 1 Hz, H ), 5.69
): = 147.7 (dd,
5, 5 = 235.7,
9 ꢆ 243 Hz, C ), 136.5 (dm,
1
3
.36; [Found: C, 64.11; H, 3.81. C14
.46%]; max (KBr): 3510, 3464, 3406, 3219, 3118, 3055, 1635, 1597,
576, 1502, 1471, 1454, 1400, 1360, 1333, 1288, 1232, 1219, 1153,
134, 1113, 1045, 962, 924, 862, 843, 820, 791, 750, 710, 634, 621,
9
H F
3
N
2
requires C, 64.12; H,
2
); C NMR (125.77 MHz, acetone-d
5 = 16.1 Hz, C ), 146.2 (dd,
C F
6 = 15.0 Hz, C ), 144.1 (dm, J 9,
6
d
1
6 = 239.0, 2J
6
1
n
J
J
J
C
C
C
C
6,
5,
10,
11,
F
C
6,
F
J
C
F
2
1
5
1
9
F
10
3
2
F
10 ꢆ 237 Hz, C ), 131.8 (d,
C F
J 7a, 6 = 11.4 Hz, C ), 127.6 (tm,
ꢃ1
1
2J
C
(d,
11
2
3
577, 482 cm ; H NMR (300.13 MHz, acetone-d
6
):
d
= 10.55 (br s,
F
10 = 15.5 Hz, C ), 126.7 (m, C ), 123.4 (d,
J
C
3a,
F
5 = 8.9 Hz,
1
2
3a
2
4
4
3
1
H, NH), 7.56 (t, 1H, J
4, 5 = 11.2, J 4, 6 = 8.0 Hz,
5 = 7.0 Hz,
H
12,
H
11 ꢆ J
H
12,
F
8 ꢆ 9 Hz, H ), 7.39 (dd, 1H,
),106.3 (d, J
C
4,
F
5 = 19.2 Hz, C ),103.7 (m, J
C
3,
9 = 15.5 Hz, C ); F NMR
= ꢃ143.7 (ddd, 1F,
4 = 8.0 Hz, F ), ꢃ144.9 (dm, 2F,
ꢃ147.8 (ddd, 1F,
7 = 7.0 Hz, F ), ꢃ162.1 (dm, 2F,
F
= 4.4 Hz, C ), 99.0
4
2
7
2
8
19
J
J
J
H
F
H
F
H ),
7.32
7.32
(dd,
(dd,
1H,
J
C
7,
F
6 = 21.9 Hz, C ), 97.8 (t,
acetone-d ):
7 = 11.0, J 6,
C F
J 8,
7
H
H
7,
7,
F
6 = 11.2, J
6 = 11.2, J
H
7,
7,
F
H ),
1H,
(282.37 MHz,
6
d
7
3
6
F
H
F
5 = 7.0 Hz, H ), 6.72 (m, 1H, J
H
3,
F
ꢆ 1.4 Hz, H ),
J
F
J
F
J
F
J
F
6,
8,
5,
9,
F
F
F
F
5 ꢆ 20, J
9 ꢆ 20 Hz,
6 = 20.2, J
F
6,
H
F
H
9
11
13
8
6
.63–6.53 (m, 2H, H , H ), 5.24 (br s, 2H, NH
2
); C NMR
F ),
F H
4 = 11.1, J 5,
1
9
5
(
100.62 MHz, acetone-d
6
):
d
= 160.6 (d, J
C
9,
F
= 244.9 Hz, C ), 150.4
F
5,
H
9
2
11
1
2
+
(
d,
J
C
11,
F
= 12.0 Hz, C ), 147.0 (dd, J
C
6,
F
6 = 237.1,
J
C
6,
F
5 = 15.8 Hz,
6 6 2
8 ꢆ 20 Hz, F ); HRMS (EI): ; , found 316.0428. C14H F N
6
1
2
2
5
C ), 146.1 (dd,
J
C
5,
F
5 = 234.4,
C
J 5,
F
6 = 14.8 Hz, C ), 135.7 (m,
6 = 10.7 Hz, C ), 128.4 (d,
5 = 8.7 Hz, C ), 110.8 (d,
F
= 12.6 Hz, C ), 105.9 (d,
9 = 25.7 Hz, C ), 99.3 (m,
6 = 21.7 Hz, C );
requires 316.0430.
3
ꢆ 2.5 Hz, C ), 131.8 (d, 3J
7a
J
J
J
J
C
C
C
C
C
2,
F
C
7a,
F
3
4
2
13
3
3a
13,
12,
F
9 = 5.8 Hz, C ), 124.5 (d,
J
C
3a,
F
4.2.9.4. 3-Fluoro-4-(4,5,7-trifluoro-1H-indol-2-yl)aniline (1ba). The
above-mentioned general procedure (Method A) was followed,
and the crude product was purified by preparative TLC (Merck
12
2
8
F
= 1.7 Hz,
C
), 107.7 (d,
C
J 8,
4
10
4,
3,
F
5 = 19.2 Hz, C ), 101.0 (d, 2J
C
10,
F
4J
= 4.7 Hz, C ), 98.7 (d,
3
2
J
7,
C F
7
19
F
NMR
1F,
1F,
precoated plates, hexane/ethyl acetate, 6:1, three times) to obtain
F
ꢅ
(
282.37 MHz,
acetone-d
12 = 9.0 Hz,
6
):
d
= ꢃ114.7
(dd,
(ddd,
1ba (109 mg, 78%) as brown solid; m.p. 178.3–179.8 C; R
f
0.26;
8
J
J
J
F
8,
6,
5,
H
9 = 13.9, J
F
8,
H
F ),
ꢃ145.6
8 4 2
[Found: C, 59.67; H, 3.21; N, 9.67. C14H F N requires C, 60.01; H,
6
F
F
F
F
5 = 20.5, J
6 = 20.5, J
F
6,
5,
H
H
7 = 11.2, J
4 = 11.2, J
F
6,
5,
H
4 = 8.0 Hz, F ), ꢃ148.7 (ddd, 1F,
2.88; N, 10.00%]; max (KBr): 3481, 3447, 3418, 3344, 3229, 3080,
n
5
+
F
F
H
7 = 7.0 Hz, F ); HRMS (EI):
;
,
2957, 2926, 2857, 1630, 1535, 1491, 1454, 1406, 1385, 1335, 1304,
1217, 1119, 1076, 997, 957, 922, 843, 816, 773, 692, 606, 569,
9 3 2
found 262.0711. C14H F N requires 262.0712.
ꢃ1
1
4
96 cm
;
H NMR (500.13 MHz, acetone-d
12, 12, 8 ꢆ 9 Hz, H ), 7.39 (ddd, 1H,
11 ꢆ J
7 = 10.4, J 6, 4 = 5.7 Hz, H ), 6.84 (m, 1H,
7 = 2.4 Hz, H ), 6.60 (dd, 1H,
6
): d= 10.92 (br s, 1H,
12
4
.2.9.2.
4-(5,6-Difluoro-1H-indol-2-yl)-2,5-difluoroaniline
NH), 7.65 (t, 1H, J
H
H
H
F
6
(1ab). The above-mentioned general procedure (Method A)
J
H
J
H
J
H
6,
3,
F
F
5 = 11.2, J
4 = 5.4, J
9 = 2.2 Hz, H ), 6.56 (dd, 1H, J
H
6,
F
H
F
3
was followed, and the crude product was purified by
preparative TLC (Merck precoated plates, hexane/ethyl acetate,
H
3,
F
J
H
11, 12 = 8.5,
H
1
1
11,
H
H
9,
F
= 14.2, J
H
9,
H
11 = 2.2 Hz,

9
6
L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
9
); 13C NMR (125.77 MHz, acetone-d
1
10 = 237.8, 2
9 = 4.1 Hz, C ), 129.4 (s, C ), 123.9 (dd,
9 = 16.4 Hz, C10), 130.2 (tt, 2
H ), 5.35 (br s, 2H, NH
2
6
):
J
J
C
C
C
10,
F
J
C
10,
F
J
C
11,
F
10 = 14.4,
7a, 7 = 15.5,
= 6.4 Hz,
7 = 23.5,
1
9
3
11
3
11
2
2
d
= 161.1 (d,
43.7 (dd,
J
C
9,
F
= 246.3 Hz, C ), 151.2 (d,
J
C
11,
F
= 12.1 Hz, C ),
11,
F
J
C
F
1
3
7
3J
C
7a
2
4 = 19.8, 3J
1
J
C
7,
F
7 = 242.3,
J
C
7,
F
5 = 11.7 Hz, C ), 142.4 (dt,
7a,
), 102.1 (d,
F
4 = 9.3 Hz, C ), 121.6 (dd,
J
C
3a,
F
C
3a,
6,
F
1
2
3
5
3a
4
3
2
5, 2J
J
C
5,
4,
F
F
5 = 234.6,
J
4,
C
5,
5 = 14.1,
9 = 5.2 Hz,
F
4 ꢆ J
C
5,
F
7 ꢆ12 Hz,
C ),
138.8
(ddd,
C
J 3,
F
= 3.5 Hz, C ), 99.3 (dd,
J
C
J 6,
F
C
F
1J
4 = 240.7, 2J
4
J
4,
F
7 = 4.0 Hz, C ), 137.0 (s, C ),
4
2
25.4 Hz, C ), 98.2 (t,
acetone-d
6
2
9 = 16.4 Hz, C ); F NMR (282.37 MHz,
= ꢃ134.6 (ddd, 1F,
7,
3 = 2.4 1 Hz, F ), ꢃ144.1 (dm, 2F,
9 ꢆ 21 Hz, F ), ꢃ148.8 (dd, 1F, J
8
19
C
C
F
C
C
8,
F
3
13
2
1
29.1 (d,
J
C
13,
F
C
), 122.1 (dd,
J
C
7a,
F
7 = 15.2,
= 6.0 Hz,
6
):
d
3
4 = 9.7 Hz, C ), 121.2 (dd, 2J
7a
4 = 20.2, 3J
7
J
C
7a,
F
C
3a,
F
C
3a,
= 12.8 Hz, C ),
F
J
J
F
7,
8,
F
4 = 20.1, J
F
7,
H
6 = 10.3, J
F
H
3
a
4
12
2
8
8
5
C
), 110.6 (d,
J
C
12,
F
= 1.6 Hz, C ), 106.7 (d,
J
C
8,
F
F
F
F
5,
4,
F
4 = 19.8, J
F H
5, 6 = 11.3 Hz, F ),
2
10
19
2
2
6
4
1
9
d
01.0 (d, J
6.6 (m,
C
10,
F
9 = 25.6 Hz, C ), 96.6 (t, J
ꢆ 6 Hz, C ); F NMR (282.37 MHz, acetone-d
C
6,
F
5 ꢆ J
C
6,
F
7 ꢆ25 Hz, C ),
ꢃ153.6 (td, 1F, J
2F, J 9,
8 ꢆ 21 Hz, F ); HRMS (EI):
requires 334.0335.
F
4,
F
5 ꢆ J
F
4,
F
7 ꢆ20, J
F
H
6 = 5.8 Hz, F ), ꢃ162.0 (dm,
4
3
9
+
J
C
3,
F
6
):
F
F
;
5 7 2
, found 334.0332. C14H F N
8
= ꢃ117.2 (m, 1F, J
F
8,
6 = 10.4, J
4 ꢆ 20, J 5, 6 = 10.7, J
4, 4, 6 = 5.7, J
7 ꢆ20, J
found 280.0616. C14
H
9 = 14.2, J
7,
3 ꢆ 3, J
5,
F
8,
H
12 = 8.6 Hz, F ), ꢃ138.8 (ddd, 1F,
7
J
F
7,
F,
4,
F
4 = 19.8, J
5,
5 ꢆ J
F
7,
H
F
H
F
7,
F
5 ꢆ1 Hz, F ), ꢃ150.0 (ddd,
5
1
J
F
F
F
H
F
F
7 ꢆ1 Hz, F ), ꢃ155.2 (tdd, 1F,
4.2.9.7.
3-Fluoro-4-(4,5,6,7-tetrafluoro-1H-indol-2-yl)aniline
4
+
J
F
F
F
F
F
H
F
4,
H
3 ꢆ 2 Hz, F ); HRMS (EI):
;
,
(1ca). The above-mentioned general procedure (Method A) was
followed, and the crude product was purified by preparative TLC
8
H F
4
N
2
requires 280.
(
Merck precoated plates, hexane/ethyl acetate, 5:1, twice) to obtain
1ca (107 mg, 72%) as light brown solid; (decomp. befor melt.); R
0.47; [Found: C, 56.41; H, 2.72; N, 8.97. C14 requires C, 56.39;
H, 2.37; N, 9.39%]; max (KBr): 3474, 3449, 3337, 3221, 2928, 1628,
4
.2.9.5.
2,5-Difluoro-4-(4,5,7-trifluoro-1H-indol-2-yl)aniline
f
(1bb). The above-mentioned general procedure (Method A)
7 5 2
H F N
was followed and the crude product was purified by preparative
n
TLC (Merck precoated plates, hexane/ethyl acetate, 5:1, twice) to
afford 1bb (89 mg, 60%) as light brown solid; m.p. 202.7 C
1543, 1487, 1456, 1423, 1389, 1346, 1319, 1281, 1227, 1169, 1146,
1130, 1043, 1001, 966, 924, 841, 795, 779, 702, 617, 600, 534,
ꢅ
ꢃ1
1
(
2
1
8
decomp.); R
928, 2852, 1645, 1593, 1568, 1537, 1495, 1456, 1441, 1408, 1335,
300, 1257, 1225, 1257, 1171, 1117, 1076, 1036, 993, 962, 926, 868,
f
0.47;
n
max (KBr): 3475, 3454, 3369, 3219, 3138, 3088,
3
465 cm ; H NMR (400.13 MHz, CDCl d= 8.89 (br s,1H, NH), 7.49
):
12
3
(t, 1H, J
6.53 (dd, 1H, J
9, = 13.9, J 9,
(100.62 MHz, acetone-d
H
12,
H
11 ꢆ J
H
12, ꢆ 3 Hz, H ),
F
8 = 9 Hz, H ), 6.78 (t, 1H, J
H
3,
F
1
1
H
11,
H
12 = 8.4, J 11, 9 = 2.3 Hz, H ), 6.47 (dd, 1H,
H H
ꢃ1
1
9
13
39, 812, 779, 746, 727, 692, 650, 611, 569, 503, 480, 432 cm ; H
): = 10.92 (br s, 1H, NH), 7.60 (dd,
8 = 6.9 Hz,
4 = 5.8 Hz, H , H ), 6.75 (dd, 1H, J
J
H
F
H
H 2
11 = 2.3 Hz, H ), 3.97 (br s, 2H, NH ); C NMR
1
9
NMR (300.13 MHz, acetone-d
1
6
d
6
):
d
= 161.7 (d, J
C
9,
F
= 246.3 Hz, C ), 152.1
1
2
3
11
1
2
H,
J
H
12,
F
11 = 12.1, J
H
12,
F
H
), 6.95–6.87 (m, 2H,
9, 8 = 12.9, J 9, 11 = 7.6 Hz,
); C NMR (100.62 MHz, acetone-d ):
12 = 1.5 Hz, C ), 148.2 (dd,
(d,
J
C
11,
F
= 12.1 Hz, C ), 139.7 (ddt,
J
C
4,
F
4 = 243.4,
J
C
4,
6, 6 = 239.0,
5 = 237.9,
7,
7 ꢆ240,
F
5 = 11.5,
6
3
3
4
4
1
J
H
6,
F
H
F
H
F
J
J
J
J
J
C
C
C
C
C
C
4,
6,
5,
7,
13,
7a,
F
F
F
6 ꢆ J
C
4,
F
7 ꢆ3 Hz,
C ),
136.7
(dtd,
J
C
F
9
13
2
2
2
3
2
3
6
1
H ), 5.36 (br s, 2H, NH
2
6
5 ꢆ J
C
6,
5,
F
7 ꢆ15,
J
C
6,
F
4 = 3.0 Hz, C ), 135.3 (dt,
J
C
5,
F
1
4
9
2
5
1
d
= 157.5 (dd,
J
C
9,
F
9 = 243.5,
12, 9 = 1.5 Hz, C ), 144.6 (ddd, J
4 = 2.7 Hz, C ), 143.2 (dt,
J
C
9,
F
4 ꢆ J
C
F
6 ꢆ16 Hz,
C ),
135.0
(ddm,
J
C F
1
4
12
1
7
3
2
J
C
C
C
C
C
C
C
12,
7,
5,
4,
11,
F
12 = 233.9,
J
C
F
C
7,
5,
4,
F
7 = 242.6,
5 = 235.0,
4 = 241.3,
(t,
F
6 ꢆ14 Hz, C ), 132.8 (d,
J
C
2,
F
9 = 4.8 Hz, C ), 129.7 (d,
3
2
2
2
2
4
7
1
C13),
2
3
J
J
J
J
J
F
5 = 11.6,
J
C
7,
F
J
C
F
F
9 = 5.2 Hz,
121.6
(td,
J
C
7a,
4 = 20.3,
F
7 ꢆ J
C
7a,
5 = 5.1 Hz,
F
4 ꢆ12,
3
5
1
3J
6 ꢆ 4 Hz, C ), 116.1 (dd, 2J
7a
3
F
4 ꢆ J
C
5,
F
7 ꢆ12 Hz,
C ),
139.8
(ddd,
J
C
F
F
C
3a,
F
J
C
3a,
F
4
4
3a
4
12
2
8
F
5 = 14.2,
J
C
4,
F
7 = 4.2 Hz,
C ),
139.2
C
), 111.4 (d,
C
J 12,
F
= 2.0 Hz, C ), 107.3 (d,
J
C
8,
ꢆ 6.5 Hz, C ); F NMR
9 ꢆ14, J 8, 12 = 8.5 Hz,
7 ꢆ18 Hz, F ), ꢃ163.3 (m, 1F,
F
9 = 12.8 Hz, C ),
3
11
2
2
10
3
3
19
F
12 ꢆ J
C
11,
F
9 ꢆ14 Hz,
C
), 136.4 (s, C ), 123.0 (dd,
101.7 (d, J 10,
C F
9 = 25.5 Hz, C ), 96.7 (t, J
):
= ꢃ117.4 (m, 1F, J
4, 4,
5 ꢆ J
4 = 16.4, J 7, 7,
5 ꢆ J
4 ꢆ 2 Hz,
7 ꢆ4 Hz, F ); HRMS (EI):
requires 298.0524.
C
3,
F
3
4 = 9.5 Hz, C ), 121.9 (dd, 2J
7a
7a,
3a,
F
7 = 15.2,
J
C
7a,
F
C
3a,
13, 9 = 5.5 Hz,
12 = 7.2 Hz, C ), 103.8 (dd,
F
4 = 19.9,
(282.37 MHz, CDCl
3
d
F
8,
H
F
H
3J
= 6.0 Hz, C ), 114.5 (dd,
3a
2
J
C
13,
8,
12 = 4.8 Hz,
12 = 22.7, 3
J
F ), ꢃ152.1 (tm, 1F, J
8
4
F
F
C
8
F
F
F
F
F
1
3
), 107.0 (dd, 2J
9 = 15.1, 3J
10,
7
C
C
8,
F
C
F
J
J
J
F
F
F
7,
6,
5,
F
6 = 19.7, J
F
7,
F
F
F
F
H
3 ꢆ 3.5 Hz, F ), ꢃ163.3 (m, 1F,
2
3
10
6
J
C
10,
3,
F
9 = 28.4,
J
C
3
F
C
),
98.4
(t,
F
F
5 ꢆ J
F
6,
5,
F
7 ꢆ20, J
4 ꢆ 20, J
F
6,
5,
F
F ),
ꢃ170.8
(td,
,
1F,
found
3J
C );
ꢆ J
4
ꢆ 7 Hz, C ), 97.9 (dd,
2
J
6,
5,
2
7 = 23.3, 25.4 Hz,
= ꢃ118.0 (m, 1F,
6 ꢆ J
5
;
+
C
6
F
C
3,
F
C
F
C
J 6,
F
F
F
F
F
19
F
NMR (282.37 MHz, acetone-d
6
8
):
d
298.0522. C14
H
7
F
5
N
2
J
J
F
8,
H
9 = 12,9, J
4 = 19.8, J
11,
F
H
8, 12 = 7.1, J 8,
F
H
3 = 5.1 Hz, F ), ꢃ135.0 (ddd, 1F,
7
F
7,
F,
F
F
7, 6 = 10.3, J 7,
12 = 12.2, J 11, 9 = 7.6 Hz,
4 = 20.2, J 5, 6 = 11.2, J 5,
7 ꢆ1 Hz, F ), ꢃ154.2 (td, 1F,
5 ꢆ J 4, 7 ꢆ20, J 4, 6 = 5.8 Hz, F ); HRMS (EI):
requires 298.0524.
H
F
H
3 ꢆ 3, J
F
7,
F
5 ꢆ1 Hz, F ), ꢃ140.2 (m,
4.2.9.8.
2,5-Difluoro-4-(4,5,6,7-tetrafluoro-1H-indol-2-yl)aniline
11
1
J
F
H
F
H
F
), ꢃ151.2 (ddd, 1F,
(1cb). The above-mentioned general procedure (Method A) was
followed, and the crude product was purified by preparative TLC
(Merck precoated plates, hexane/ethyl acetate, 5:1, five times) to
5
J
J
F
5,
4,
F
F
H
F
F
4
+
F
F
F
F
F
H
; , found
2
98.0526. C14
H
7
F
5
N
2
obtain 1cb (115 mg, 73%) as white solid; (decomp. befor melt.); R
.70; max (KBr): 3537, 3510, 3477, 3415, 2928, 2854, 1645, 1614,
1545, 1491, 1454, 1423, 1340, 1227, 1178, 1140, 1115, 995, 928, 872,
f
0
n
4.2.9.6. 2,3,5,6-Tetrafluoro-4-(4,5,7-trifluoro-1H-indol-2-yl)aniline
ꢃ1
1
(1bc). The above-mentioned general procedure (Method B) was
796, 779, 669, 640, 604, 542, 507, 467 cm ; H NMR (400.13 MHz,
acetone-d ): = 11.11 (br s, 1H, NH), 7.58 (dd, 1H,
11 = 12.2, J
4 = 5.5, J 3,
8 = 12.9, J 9,
followed, and the crude product was purified by preparative TLC
6
d
1
2
(
1
Merck precoated plates, hexane/ethyl acetate, 5:1, twice) to obtain
J
J
J
H
H
H
12,
F
H
12,
7 ꢆ3 Hz,
11 = 7.6 Hz, H ), 5.37 (br s, 2H, NH
F
8 = 7.0 Hz,
H
),
6.88
6.74
(dd,
1H,
1H,
ꢅ
H3),
bc (95 mg, 57%) as light brown solid; m.p. 189.6 C (decomp.); R
f
3,
9,
F
H
F
(dd,
9
); 13C NMR
0
.50;
nmax (KBr): 3485, 3410, 3203, 3088, 2929, 1664, 1605, 1539,
F
H
F
2
1
9
1
514, 1495, 1444, 1400, 1336, 1313, 1300, 1207, 1176, 1124, 1086,
(100.62 MHz, acetone-d
6
):
d
= 157.4 (d, J
C
9,
F
= 243.5 Hz, C ), 148.2
ꢃ1
1
1
4
12
1005, 987, 964, 937, 818, 796, 719, 687, 615, 579, 467 cm ; H NMR
(dd,
J
C
12,
4 = 244.0,
12 = 15.2,
F
12 = 235.6,
J
C
12,
F
9 = 1.6 Hz,
C ), 140.2 (ddt,
1
2
3
4
4
(
300.13 MHz, acetone-d
6
):
d
6,
= 11.11 (br s, 1H, NH), 7.03 (ddd, 1H,
J
J
J
J
J
C
C
C
C
C
C
4,
11,
6,
5,
F
J
C
4,
F
5 = 11.5,
J
C
4,
F
6 ꢆ J
C
4,
F
7 ꢆ4 Hz, C ), 139.2 (t,
6
2
2
1
1
3
11
1
J
J
H
6,
3,
F
5 = 11.0, J
H
6,
F
7 = 10.4, J
H
F
4 = 5.8 Hz, H ), 6.92 (m, 1H,
F
J
C
11,
F
9 = 12.7 Hz, C ), 137.0 (dtm,
J
C
6,
F
6 = 239.7,
3
); 13C NMR (125.77 MHz,
2
3
6
2
H
F
= 1.5 Hz, H ), 5.79 (br s, 2H, NH
2
F
5 ꢆ J
C
6,
F
7 ꢆ14,
C F
J 6, 4 = 3.0 Hz, C ), 136.4 (m, C ), 135.4 (dt,
1
9
2
2
5
acetone-d
6
):
7 = 243.4,
5 = 235.7,
4 = 242.7, 2J
d
= 146.0 (dm,
J
C
9,
F
9 ꢆ 245 Hz, C ), 145.3 (ddd,
F
5 = 238.4,
J
C
5,
F
4 ꢆ J
C
5,
F
7
6 ꢆ16 Hz,
C ),
135.1 (ddm,
1
3
4
7
7 ꢆ245, 2J
2
3
J
C
J
C
C
7,
5,
4,
F
J
C
7,
F
5 = 11.7,
J
C
7,
F
4 = 2.7 Hz, C ), 143.8 (dt,
7,
7a,
F
C
7,
F
7a
6 ꢆ16 Hz, C ), 121.8 (td,
J
C
7a,
F
7 ꢆ J
C
7a,
F
4 ꢆ11,
3a
1
2
3
5
3J
2
3
F
J
C
5,
F
4 ꢆ J
C
5,
F
7 ꢆ11 Hz,
C ),
140.3
(ddd,
F
6 ꢆ 4 Hz, C ), 116.1 (dd, J
C
3a,
F
4 = 20.0, J
9 = 5.5 Hz, C ), 106.8 (dd,
C
3a, 5 = 4.8 Hz, C ),
F
1J
4, 5 = 14.3,
4
J
7 = 4.5 Hz, C ), 138.2 (dm,
4
114.4 (dd,
2
J
13,
12 = 22.8,
3
J
13,
13
F
C
F
C
4,
F
C
F
C
F

L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
97
2
9 = 15.1, 3J
12 = 4.8 Hz,
8
2
7
+
J
C
8,
10,
F
C
8,
F
12 = 7.2 Hz, C ), 103.8 (dd,
J
C
10,
F
9 = 28.4,
J
C
F
7,
F
6 = 20.2, J
F
7,
F
4 = 17.7 Hz, F ); HRMS (EI):
;
, found 348.0487.
3J
C
10
), 97.8 (t, 3J
acetone-d ):
12 = 7.0 Hz,
11, 9 = 7.6 Hz,
7 = 16.5, J 4, 6, J
7, 4 = 16.5, J 7,
5 ꢆ J
7 ꢆ19, J 6, 4 ꢆ 2 Hz,
4 ꢆ19, J 5, 7 ꢆ4 Hz, F ); HRMS (EI):
requires 316.0430.
ꢆ 8 Hz, C );
3
19
F
NMR
1F,
requires 348.0492.
C
F
C
3,
F
15
7
H F
7
N
2
(
376.46 MHz,
8, 9 = 13.3, J
11, 12 = 12.2, J
4, 4,
5 ꢆ19, J
7, 6 = 19.8, J
6
d
= ꢃ118.2
ꢃ140.2
(m,
(m,
(tm,
8
J
J
J
J
J
J
F
H
F
8,
H
F ),
1F,
1F,
4.2.9.11.
indol-2-yl)aniline
2,5-Difluoro-4-(4,6,7-trifluoro-5-(trifluoromethyl)-1H-
(1db). The above-mentioned general
procedure (Method A) was followed, and the crude product was
purified by preparative TLC (Merck precoated plates, hexane/ethyl
acetate, 5:1, twice) to obtain 1db (148 mg, 81%) as light brown
F
11),
ꢃ151.3
F
F
F
F
F
H
F
H
4
F
F
F
F
F
F
4,
H
3 ꢆ 2 Hz, F ), ꢃ160.4 (tm, 1F,
7
F
F
F
F
F
F
7,
H
3 ꢆ 4 Hz, F ), ꢃ167.9 (td, 1F,
6
6,
5,
F
F
5 ꢆ J
F
6,
5,
F
F
F
F ),
ꢃ170.9
(td,
1F,
found
5
+
ꢅ
6 ꢆ J
F
F
F
F
;
,
solid; 188.3–189.8 C; R
C
3
f
0.64; [Found: C, 49.53; H, 1.66; N, 7.46.
max (KBr): 3523,
473, 3427, 3211, 3141, 2926, 2856, 1645, 1614, 1525, 1498, 1456,
3
16.0428. C14
H
6
F
6
N
2
15 6 8 2
H F N requires C, 49.20; H, 1.65; N, 7.65%]; n
4
.2.9.9.
2,3,5,6-Tetrafluoro-4-(4,5,6,7-tetrafluoro-1H-indol-2-yl)
1406, 1352, 1311, 1277, 1252, 1207, 1165, 1120, 1024, 999, 928, 874,
ꢃ1
1
aniline (1cc). The above-mentioned general procedure
Method C) was followed, and the crude product was purified by
837, 793, 742, 717, 646, 519 cm ; H NMR (400.13 MHz, acetone-
): = 11.27 (br s, 1H, NH), 7.50 (dd, 1H,
12, 11 = 12.1, J 8 = 7.1 Hz, H ), 6.80 (t, 1H, J 3,
ꢆ 3 Hz, H ),
6.68 (dd, 1H, J 9, 11 = 7.6 Hz, H ), 5.32 (br s, 2H, NH );
= 243.9 Hz,
12 = 234.1,
(
d
6
d
1
2
3
preparative TLC (Merck precoated plates, hexane/ethyl acetate, 5:1,
three times) to obtain 1cc (125 mg, 71%) as white solid; m.p.
J
H
F
H
12,
8 = 13.0, J
F
H
F
9
H
F
H
9,
F
2
ꢅ
13
1
216.4 C (decomp.); R
f
0.67;
nmax (KBr): 3520, 3487, 3419, 3190,
6 C F
C NMR (125.77 MHz, acetone-d ): d= 157.5 (d, J 9,
9
1
4 = 258.4 Hz, C ), 148.2 (dd, 1J
4
2
926, 2854, 1664, 1608, 1545, 1522, 1491, 1419, 1342, 1317, 1242,
C ), 148.6 (dm,
J
C
4,
F
C
12,
F
4
12
1
2
1176, 1101, 1082, 1005, 980, 935, 795, 721, 677, 633, 604, 565,
J
C
12,
F
9 = 1.3 Hz, C ), 142.9 (ddd,
4 = 1.4 Hz, C ), 139.3 (dd,
), 136.7 (s, C ), 135.3 (ddd,
J
C
6,
F
6 = 246.0,
J
C
6,
F
7 = 13.7,
J 11, 9 = 12.8 Hz,
ꢃ1
1
3J
6
2
3
4
47 cm
;
H NMR (400.13 MHz, acetone-d
6
):
d
= 11.31 (br s, 1H,
C
11
6,
F
J
C
11,
F
12 = 15.3,
C F
3
13
2
1
2
NH), 6.91 (m, 1H, J
H
3,
100.62 MHz, acetone-d
F
ꢆ 3 Hz, H ), 5.80 (br s, 2H, NH
2
); C NMR
C
J
C
7,
F
7 = 243.9,
J
C
7,
F
6 = 16.3,
7a,
4 ꢆ12,
), 117.4 (dd,
13, 12 = 22.9,
F C F
9 = 15.0, J 8, 12 = 7.3 Hz, C ),
1
9
4
7
2
3
(
6
):
d
= 145.3 (dm,
5 = 11.4, 3
4,
J
C
9,
F
9 ꢆ 244 Hz, C ),
J
C
C
C
C
7,
F
4 = 4.0 Hz,
C ),
128.5
(tm,
J
C
7a,
F
7 ꢆ J
C
F
1
2
4
4
3
6 ꢆ 5 Hz, C ), 123.5 (q, 1JCF3
7a
139.2 (ddt, J
C
4,
F
4 ꢆ 248,
J
C
4,
F
J
C
F
6 ꢆ J
C
4,
F
7 ꢆ4 Hz, C ),
J
7a,
3a,
13,
F
F
F
,
F
= 272.0 Hz, CF
3
1
10
1
6
2
3
3a
2
137.4 (dm, J
C
10,
F
10 ꢆ 238 Hz, C ),137.3 (dm, J
C
6,
F
6 = 240.6 Hz, C ),
J
4 = 23.6,
J
C
3a,
F
7 = 4.4 Hz, C ), 114.1 (dd,
J
C
F
1
2
2
5
3J
13
2
3
8
1
35.5 (dt,
J
C
5,
F
5 = 239.1,
J
C
5,
F
4 ꢆ J
C
5,
F
6 ꢆ15 Hz, C ), 135.1 (ddm,
9 = 5.4 Hz, C ), 106.3 (dd, J
C
8,
10, 12 = 4.8 Hz,
6 = 13.8 Hz,
= 10.2 Hz, C ); F NMR (376.46 MHz, acetone-d
4 = 24.3, JCF3 6 = 20.6 Hz, CF
), ꢃ117.7 (m, 1F,
8, 12 = 7.1 Hz, (m, 1F,
ꢃ124.9
4, 7 = 18.0, J 4,
12 = 12.1, J 11, 9 = 7.6 Hz,
6, 6, 4 = 5.6 Hz,
7 ꢆ20, J
6 = 19.1, J 7, 4 = 18.0 Hz, F ); HRMS (EI):
requires 366.0398.
1
3
2
2
7
2
2
3
10
J
J
J
C
C
C
C
7,
11,
7a,
3a,
F
7 = 245.5,
9 = 4.3 Hz,
J
C
7,
F
6 = 13.5 Hz, C ), 129.7 (tt,
J 11,
C F
10 = 14.5,
103.7 (dd,
J
C
10,
F
9 = 28.4,
J
5,
C
F
C
), 99.0 (m,
98.4 (d,
):
= ꢃ53.5
11
2
2
2
2J
5
F
C
),
128.8
(s,
6 ꢆ 4 Hz,
C ),
122.1
115.3
(td,
J
C
5,CF3 = 33.1,
J
C
5,
F
4,
C
F
C ),
3
3J
7a
3J
3
19
F
7 ꢆ J
C
7a,
F
3
4 ꢆ11,
C
7a,
F
C
),
(dd,
C
3,
F
6
d
2J
4 = 20.2,
J
3a,
5 = 4.6 Hz, C ), 101.1 (t, 3J
3a
ꢆ 2 Hz, C ),
3
(dd, 3F,
J
,
,
F
C
F
C
3,
F
CF3
F
F
3
2
8
19
8
9
d
7.5 (t,
= ꢃ144.2 (dm, 2F,
4, 4, 7 = 16.4, J
5 ꢆ19, J
7, 6 = 19.4, J 7, 4 = 16.6, J
9,
8 ꢆ 21 Hz, F ), ꢃ166.6 (t, 1F, J
5, 5, 4 ꢆ19, J 5, 7 ꢆ4 Hz, F ); HRMS (EI):
6 ꢆ J
52.0246. C14 requires 352.0241.
J
C
8,
F
9 = 16.0 Hz, C ); F NMR (376.46 MHz, acetone-d
6
):
J
F
J
F
J
F
J
F
J
F
8,
4,CF3 = 24.3, J
11,
H
9 = 13.0, J
F
H
F ),
8
4
J
4,
F
8,
6, J
7,
5 ꢆ J
F
9 ꢆ 21 Hz, F ), ꢃ150.6 (tm, 1F,
F
F
F
F
6 = 5.6 Hz, F ), ꢃ140.2 (m, 1F,
4
11
J
F
J
F
J
F
F
F
F
F
F
F
4,
H
3 ꢆ 2 Hz, F ), ꢃ159.9 (tm, 1F,
H
F
H
F
),
F ),
ꢃ150.2
(m,
(m,
1F,
1F,
7
6
F
F
F
9
F
F
F
7,
6,
H
3 ꢆ 4 Hz, F ), ꢃ162.9 (dm, 2F,
6,CF3 ꢆ J
F
F
F
F
ꢃ161.2
6
7
+
F
F
F
5 ꢆ J
F
6,
F
7 ꢆ19 Hz, F ), ꢃ170.4
7,
F
F
F
;
, found 366.0396.
5
+
(
td, 1F, J
F
F
F
F
F
F
;
, found
C
15
H
6
F
8
N
2
3
4 8 2
H F N
4
.2.9.12.
2,3,5,6-Tetrafluoro-4-(4,6,7-trifluoro-5-(trifluoromethyl)-
4
.2.9.10. 3-Fluoro-4-(4,6,7-trifluoro-5-(trifluoromethyl)-1H-indol-2-
1H-indol-2-yl)aniline (1dc). The above-mentioned general
procedure (Method C) was followed, and the crude product was
purified by preparative TLC (Merck precoated plates, hexane/ethyl
acetate, 5:1) to obtain 1dc (109 mg, 54%) as white solid; 137.2 C
f
(decomp.); R 0.55; nmax (KBr): 3522, 3479, 3423, 3199, 3167, 2966,
yl)aniline (1da). The above-mentioned general procedure
Method A) was followed, and the crude product was purified
(
ꢅ
by preparative TLC (Merck precoated plates, hexane/ethyl acetate,
ꢅ
10:1, twice) to obtain 1da (127 mg, 73%) as brown solid; 141.6 C
(
decomp.); R
requires C, 51.74; H, 2.03; N, 8.04%];
235, 3146, 2959, 2920, 2853, 1659, 1636, 1585, 1526, 1493, 1466,
454, 1354, 1325, 1288, 1246, 1211, 1177, 1124, 1097, 997, 961, 926,
f
0.20; [Found: C, 51.80; H, 2.34; N, 8.03. C15
H
7
F
7
N
2
2937, 2877, 1664, 1610, 1522, 1495, 1462, 1396, 1358, 1323, 1267,
1215, 1174, 1126, 1078, 1003, 937, 883, 802, 748, 712, 679, 644, 611,
nmax (KBr): 3478, 3426, 3362,
ꢃ1
1
3
1
8
532, 515, 490 cm
(br s, 1H, NH), 7.01 (m, 1H, J
NMR (125.77 MHz, acetone-d
;
H NMR (300.13 MHz, acetone-d
6
):
d= 11.68
3
13
H
3,
F
ꢆ 3 Hz, H ), 5.87 (br s, 2H, NH
2
);
C F
d= 149.0 (dm, J 4, 4 = 257.0 Hz,
C
ꢃ1
1
1
72, 851, 822, 793, 743, 719, 631, 611, 507, 447 cm
):
8 = 9 Hz, H ), 6.82 (t, 1H, J
;
H NMR
6
):
9 ꢆ 244 Hz, C ), 143.3 (ddd,
4
1
9
1
(
400.13 MHz, CDCl
12, 12,
11 ꢆ J
dd, 1H, 11,
9, 8 = 14.0, J 9,
125.77 MHz, acetone-d
3
d
= 9.10 (br s, 1H, NH), 7.49 (t, 1H,
C ), 145.3 (dm,
J
C
9, 6,
4 = 4.7 Hz, C ), 137.3 (dm, J 10, 10 = 237 1 Hz,
F
J
C
F
6 = 246.9,
12
3
2
3
6
1
J
H
H
H
F
H
3,
F
ꢆ 3 Hz, H ), 6.54
J
C
C
6,
F
7 = 13.9,
J
C
6,
F
C F
1
1
10
1
2
4
7
(
J
H
H
12 = 8.5,
J
H
11,
H
9 = 2.2 Hz,
H
), 6.47 (dd, 1H,
), 135.5 (ddd, J 7 = 244.4, J 6 = 16.6, J 7, 4 = 4.2 Hz, C ),
C F C F C F
7, 7,
C F
10 = 14.6, J 11, 9 = 4.2 Hz, C ), 129.5 (m, C ), 128.9
9
); 13C NMR
2
3
11
2
J
H
F
H
H
11 = 2.2 Hz, H ), 4.00 (br s, 2H, NH
2
130.0 (tt, J
(tm, J
116.8 (dd, J
C
11,
F
3
1
9
2
7a
1
(
(
(
6
):
d
= 160.8 (d, J
C
9,
F
= 246.7 Hz, C ), 151.2
C
7a,
F
7 ꢆ J
C
7a,
4 = 24.5, J
F
4 ꢆ14 Hz, C ), 123.5 (q, JCF3
F 3
, = 272.0 Hz, CF ),
3
11
1
4
2
3
3a
3
d,
J
C
11,
F
= 12.2 Hz, C ), 147.6 (dm,
6 = 245.7, J
7 = 243.7, J
C
J 4,
F
4 = 256.0 Hz, C ), 141.6
C
3a,
5,CF3 = 33.4,
9 = 16.7 Hz, C8);
= ꢃ53.6 (dd, 3F, JCF3
1F, J 4,CF3 = 24.7, J 4, 7 = 18.1, J
8,
9 ꢆ 20 Hz, F ), ꢃ149.2 (m, 1F, J
F ), ꢃ160.7 (td, 1F, J 7, 6 ꢆ J 7, 4 = 18.4, J
(dm, 2F, J 9,
8 ꢆ 21 Hz, F ); HRMS (EI):
requires 402.0209.
F
C
3a,
F
7 = 4.3 Hz, C ), 102.0 (m, C ), 99.4
1
2
3
6
2
2
2
5
ddd, J
C
6,
F
C
6,
F
7 = 13.6, J
C
6,
F
4 = 4.4 Hz, C ), 134.2 (ddm,
(m,
J
C
J
C
5,
F
F
4,
C
J 5,
F
6 ꢆ13 Hz, C ), 97.0 (t,
1
2
4
7
2
2
19
J
C
7,
F
C
7,
F
6 = 16.2, J
C
7,
F
4 = 4.0 Hz, C ), 137.0 (s, C ), 128.6
J
C
8,
F
6
NMR (282.37 MHz, acetone-d ):
3
13
2
3
(
d,
C
J 13,
F
9 = 5.0 Hz,
C
), 127.4 (tm,
J
C
7a,
F
7 ꢆ J
C
7a,
F
4 ꢆ12,
d
,
F
4 = 24.7, JCF3
4,
6 = 5.3 Hz, F ), ꢃ144.1 (dm, 2F,
6,CF3 ꢆ J 6, 7 ꢆ20, J 6, 4 = 5.3 Hz,
7,
3 = 2.6 Hz, F ), ꢃ161.9
,
F
6 = 20.6 Hz, CF
3
), ꢃ123.8 (m,
3
7a
1
4
J
C
7a,
3a,
05.8 (d, J
F
6 ꢆ 5 Hz, C ), 122.4 (q,
J
CF3
3a
,
F
= 272.0 Hz, CF
3
), 116.5 (dd,
F
F
F
F
F
2J
1
4 = 23.6,
3
J
7 = 4.6 Hz, C ), 110.3 (d,
4
J
12,
ꢆ 2 Hz, C ),
12
J
8
C
F
C
3a,
F
C
F
F
F
F
F
F
F
F
7
2
8
2
10
6
C
8,
F
9 = 12.8 Hz, C ), 101.6 (d, J
C
10,
6 = 14.0 Hz, C ), 96.3 (d,
F
9 = 25.5 Hz, C ), 97.8
F
F
F
F
F H
2
2
2
5
9
+
(
m,
J
C
5,CF3 = 33.0,
J
C
5,
= 8.7 Hz, C ); F NMR (282.37 MHz, CDCl
4 = 24.4, JCF3 6 = 20.6 Hz, CF ),
9 ꢆ14, J 8, 12 = 8.5 Hz, ꢃ122.8
4, 7 = 17.7, J 4,
3 = 2.4 Hz, F ), ꢃ147.1 (m,
6,CF3 ꢆ J 6, 7 ꢆ20, J 6,
F
4,
J
5,
C F
F
F
; , found 402.0212.
3
3
19
J
F,
8,
C
3,
F
3
):
d
= ꢃ53.0 (dd,
15 4 10 2
C H F N
3
J
CF3
,
F
,
F
3
ꢃ114.2
(m, 1F,
8
J
J
F
H
F
H
F ),
(m,
1F,
Acknowledgments
4
F
4,CF3 = 24.4, J
F,
F
F
F
F
F H
6 = 5.3, J 4,
6
1
J
F
F
F
F
F
4 = 5.3 Hz, F ), ꢃ161.2 (m, 1F,
The authors thank the Russian Foundation for Basic Research for
financial support (grant 14-03-00108) and the Multi-Access

9
8
L.V. Politanskaya et al. / Journal of Fluorine Chemistry 188 (2016) 85–98
Chemical Service Center SB RAS for spectral and analytical
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