Synthesis of polyfluorinated ortho-alkynylanilines

Article abstract of DOI:10.1016/j.jfluchem.2011.09.008

A series of polyfluorinated ortho-alkynylanilines - the versatile building blocks for diverse polyfluorobenzo azaheterocycles - have been synthesized by the Sonogashira reaction of polyfluorinated ortho-iodanilines with terminal alkynes.

Full text of DOI:10.1016/j.jfluchem.2011.09.008

Journal of Fluorine Chemistry 135 (2012) 97–107
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of polyfluorinated ortho-alkynylanilines
Larisa V. Politanskaya a, Igor P. Chuikov a, +katerina !. Kolodina b,
Mark S. Shvartsberg b, Vitalij D. Shteingarts a,
*
a N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, Ac. Lavrentiev Avenue 9, 630090 Novosibirsk, Russian Federation
b A.A. Kovalsky Institute of Chemical Kinetics and Combustion, Siberian Branch of Russian Academy of Sciences, Institutskaya Str. 3, 630090 Novosibirsk, Russian Federation
A R T I C L E I N F O
A B S T R A C T
series of polyfluorinated ortho-alkynylanilines
Article history:
A
– the versatile building blocks for diverse
Received 22 July 2011
polyfluorobenzo azaheterocycles – have been synthesized by the Sonogashira reaction of polyfluori-
nated ortho-iodanilines with terminal alkynes.
Received in revised form 9 September 2011
Accepted 15 September 2011
Available online 29 September 2011
ß 2011 Elsevier B.V. All rights reserved.
Keywords:
Polyfluorinated ortho-iodanilines
Polyfluorinated ortho-alkynylanilines
Terminal alkynes
Iodination
Sonogashira coupling
1. Introduction
for diverse constructions of both five- and six-membered azahe-
terocycles. This is of special importance for synthesis of indoles
Fluorinated benzoazaheterocycles are molecular cores of many
bioactive compounds, including active substances of medicines [1–
5]. Therefore, fluorine introduction in the benzene moiety of a
benzoheterocycle is an important structural modification in the
molecular design of bioactive compounds. In this respect
compounds of this type with a polyfluorinated benzene ring are
of their own importance as accumulation of fluorine atoms can
both essentially modify bioactivity and also afford nice opportu-
nities to functionalize the scaffold by nucleophilic substitution of
fluorine. However, until recently this area was in its infancy,
obviously, because of a small accessibility of one of the versatile
precursor types for the diversity of polyfluorobenzo azahetero-
cycles – anilines containing 3–4 fluorine atoms and a nonsub-
stituted position ortho to the amino group. This obstacle was
recently substantially minimized by developing the selective
ortho-defluorination of polyfluoroaniline N-acetyl derivatives [6,7]
and dechlorination of polyfluorochloroanilines [8]. In particular,
this allowed starting the systematic exploration of quinolines
polyfluorinated on the benzene ring [7–11].
polyfluorinated on the benzene ring, as above achievements in the
synthesis of ortho-unsubstituted polyfluoroanilines are not suffi-
cient to surmount their scarce accessibility by virtue of difficulty of
the Fisher indole assembling on the basis of polyfluorinated anilines
[12,13] which originates from the very nature of these building
blocks as polyfluoroarenes. As a consequence, though the Fisher
indole syntheses from anilines containing up to 2 fluorine atoms are
amply presented in literature [14–16], to the best of our knowledge,
only two indoles with the perfluorinated benzene ring were
prepared till now, both with the substituted pyrrole moiety [17].
4,5,6,7-Tetrafluoroindole itself was synthesized from hexafluoro-
benzene via a different multistep course [18], applicability of which
for a wide range of similar compounds being at least not obvious.
By virtue of aforementioned, the methods draw attention which
are based on reactions catalysed by transition metal complexes, the
cyclizations of ortho-alkynylanilines [19–25] or their N-derivatives
[19,20,26–32] seeming most attractive. Such starting materials can
be got from the catalytic cross-condensation of ortho-haloanilines
(preferably, iodoanilines)with terminal alkynes [32,33] and used for
synthesis of a vast diversity of benzoazaheterocycles [34,35]. Only
few applications of the approach to the polyfluorinated building
blocks of this type were reported [25,32–34], apparently, owing to
their previous poor accessibility. Fortunately, the above develop-
ment of a general concise route to the ortho-nonsubstituted
polyfluoroanilines cancels this restriction, thus rendering the
corresponding polyfluorinated ortho-halonanilines and, potentially,
ortho-alkynylanilines, on their ground, quite accessible.
Thescopeofmethodsforazaheteroannelationcanappreciablybe
extended by incorporating various structural units suitable for
heterocyclization in the position ortho to the amino group. Among
those, the alkynyl groups are especially attractive because can serve
* Corresponding author. Fax: +7 383 3309752.
E-mail address: shtein@nioch.nsc.ru (V.D. Shteingarts).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.09.008

98
L.V. Politanskaya, I.P. Chuikov / Journal of Fluorine Chemistry 135 (2012) 97–107
Table 1
In this connection, the purpose of the present work is to
Iodination of anilines 1a–d (I2 + HIO3, aq. dioxane, 70 8C).
examine a possibility to synthesize polyfluorinated ortho-alkyny-
lanilines from corresponding ortho-haloanilines via the Sonoga-
shira reaction.
Entry
Substrate
Product
Time (h)
Yield (%)
97
1
4
2. Results and discussion
2.1. Iodination of polyfluoroanilines
As starting materials we used 2,3,5-trifluoro-4-(trifluoro-
methyl)aniline 1a [6], 2,3,4,5-tetrafluoroaniline 1b [6], 2,4,5-
trifluoroaniline 1c [11], 2,4-difluoroaniline 1d [36] and commer-
cial 3,4-difluoroaniline 1e. To iodinate these amines [37], iodine
was preferred to use as more convenient in comparison with iodine
chloride which was applied earlier to prepare 2-iodo-4,5-
difluoroaniline (2e) [32] and 2-iodo-3,4,5,6-tetrafluoroaniline
(2b) [38] from amines 1e and 1b, respectively. Although 2-iodo-
4,5-difluoroaniline 2e was smoothly prepared from aniline 1e by
the protocol [39] (I2–NaHCO3–H2O, r.t.), aniline 1d gave no a
iodination product with this reagent even at reflux. Therefore, the
silver sulfate additive (I2–Ag2SO4–EtOH, reflux) was used in
iodination of aniline 1a to obtain 2-iodo-3,5,6-trifluoro-4-(tri-
fluoromethyl)aniline (2a) in 93% yield (Scheme 1). However,
probably owing to a high reactivity, this system turned out
nonselective in iodination of aniline 1c: even at an incomplete
consumption of the starting compound (14% in the resulting
mixture) a GC–MS analysis revealed the formation of both isomeric
mono-(43% ortho and 8% meta) and diiodinated (32%) products.
Proceeding from these results, the combination of iodine and iodic
acid in aqueous dioxane was found nicely appropriate for the
selective monoiodination of anilines 1a–d to afford anilines 2a, 2b,
2-iodo-3,4,6-trifluoroaniline (2c) and 2-iodo-4,6-difluoroaniline
(2d) in 88–97% yields (Scheme 1 and Table 1). The structures of 2a–
e are unequivocally evidenced from their 1H and 19F NMR
characteristics which are discussed below.
Besides the synthetic value, the above results are of interest to
compare the reactivity of the iodination systems and substrates. It
seems obvious that, in all the cases, the iodination is electrophilic,
so that the respective reagents should be considered as equivalents
of the cationic I+ synthon (actually, solvated I3+) with a reactivity
depending on a nature of the counterion and solvent. The relatively
high basicity of the I2–NaHCO3–H2O system causes the strongest I+
association with the counterion and the solvent among the
iodination systems we used. As a result, its lowest reactivity among
the used iodination systems allows to iodinate only aniline 1e –
certainly most reactive of the substrates under study. In turn, the
fact that isomeric aniline 1d failed to be iodinated by this system
elucidates clearly the reaction to be crucially retarded by switching
2
3
4
3
3
3
88
97
95
from an activating electron-donating effect of the fluorine para to
the reaction site to a deactivating electron-withdrawing effect of
the meta fluorine. As mentioned above, the I2–Ag2SO4–EtOH
system appeared most active among the iodination systems under
application, likely due to strong counterion binding by an Ag+
cation, the I+ cation thus being relatively weakly associated with I2
or solvent molecules. The I2–HIO3–aq. dioxane system manifests
the medium reactivity obviously due to the association of the I+
cation with counterion and solvent in this system is weaker
compared with the more basic I2–NaHCO3–H2O system and
stronger compared with the less basic I2–Ag2SO4–EtOH system.
The high reactivity and, consequently, low selectivity of the I2–
Ag2SO4–alcohol system is probably responsible for the comparably
low and unnaturally substituent-dependent yields of the selective
ortho iodination products obtained from 4-X-anilines (X = H 46%,
Me 41%, Cl 73%, NO2 75%) by using the I2–Ag2SO4–1,2-ethanediol
system [40]. In turn, the high selectivity of the I2–HIO3 system is in
line with numerous examples of the selective iodination of
substituted phenols [41,42] and 5- or 6-amino-1,4-naphthoqui-
nones [43] at the positions ortho or para to the OH and NH2 group,
accordingly.
Scheme 1.

L.V. Politanskaya, I.P. Chuikov / Journal of Fluorine Chemistry 135 (2012) 97–107
99
Table 2
Synthesis of alkynylanilines 4a–e,f–i.
Entry
1
Substrate
Alkyne
Product
Time (h)
3
Yield (%)
2a
73
2
3
2a
2a
3
3
78
81
4
2a
3
76
5
2b
3f
3
89
6
7
2b
2b
3g
3h
3
3
80
82
8
2b
3i
3
85
9
2c
3f
3
90
10
11
2c
2c
3g
3h
3
3
80
91

100
L.V. Politanskaya, I.P. Chuikov / Journal of Fluorine Chemistry 135 (2012) 97–107
Table 2 (Continued )
Entry
12
Substrate
Alkyne
Product
Time (h)
3
Yield (%)
83
2c
3i
13
2d
3f
3
72
14
15
2d
2d
3g
3h
3
3
73
77
16
2d
3i
3
70
17
2e
3f
3
74
18
19
2e
2e
3g
3h
3
3
95
92
20
2e
3i
3
73
Summing up, we demonstrate a high efficiency of the I2–HIO3
system in the selective iodination of polyfluorinated 2-H-anilines
affording respective polyfluorinated 2-iodoanilines which are
believed to be valuable versatile starting materials to synthesize
a wide diversity of ortho functionalized polyfluoroanilines.
(Scheme 1). According to 19F NMR and GC–MS analyses, conversion
of all the starting compounds to the ortho-alkynylanilines 4a–e,f–i
was complete, and the corresponding diynes derived by alkynes
homo-coupling (cf. [44]) were present in the product mixtures. The
target compounds 4 were isolated by TLC (Table 2).
Though the principal goal of the work has been achieved by the
synthesis of alkynylanilines 4a–e,f–i, the evaluation of substitu-
ent effects in the Sonogashira coupling is of interest. 2-Bromo-4,6-
difluoroaniline, 2-bromo-4-nitro-6-chloroaniline and 2-bromo-
5-(trifluoromethyl)aniline were reported to react with ethynyl-
trimethylsilane in the presence of Pd(PPh3)2Cl2, CuI and Et3N in
2.2. Polyfluorinated 2-iodoanilines in the Sonogashira coupling
In development of the latter possibility, all the ortho-iodoanilines
2a–e were subjected to cross-coupling with terminal alkynes 3f–i in
Et3N with Pd(PPh3)2Cl2 (4 mol.%) and CuI (9 mol.%) as catalysts

L.V. Politanskaya, I.P. Chuikov / Journal of Fluorine Chemistry 135 (2012) 97–107
101
Table 3
1H and 19F NMR chemical shifts (ppm) and coupling constants (Hz) for anilines 2a–e and 5 (CDCl3).
Compound
NH2
R3
R4
R5
R6
2a
4.93 (s)
–95.2 (qd, 1F)
JF3,CF3 = 21.6
JF3,F6 = 9.8
–56.4 (dd, 3F)
JCF3,F3,
–141.6 (dq, 1F)
–161.0 (dd, 1F)
JF6,F5 = 19.4
JF6,F3 = 9.9
JF5,CF3
,
JCF3,F5 ꢂ 22
JF5,F6 ꢂ 22
2b
2c
2d
2e
5
4.13 (s)
–119.5 (ddd, 1F)
JF3,F4 = 23.7
JF3,F6 = 7.9
–171.0 (ddd, 1F)
JF4,F3 = 23.7
JF4,F5 = 20.7
JF4,F6 = 5.4
–157.6 (ddd, 1F)
JF5,F6,
–159.1 (ddd, 1F)
JF6,F5 = 19.9
JF6,F3 = 7.9
JF5,F4 ꢂ 20.5
JF5,F3 = 3.0
JF3,F5 = 3.0
JF6,F4 = 5.4
4.08 (s, 2H)
3.96 (s, 2H)
4.00 (s, 2H)
4.77 (s)
–121.6 (ddd, 1F)
JF3,F4 = 23.4
JF3,F6 = 11.5
JF3,H5 = 7.2
–148.0 (ddd, 1F)
JF4,F3 = 23.5
JF4,H5 = 9.7
6.96 (ddd, 1H)
JH5,F4,
–134.2 (ddd, 1F)
JF6,F3, JF6,H5 ꢂ 11
JF6,F4 = 2.5
JH5,F6 ꢂ 10
JH5,F3 = 7.2
JF4,F6 = 2.5
7.11 (ddd, 1H)
JH3,F4 = 7.8
–125.5 (dd, 1F)
6.74 (ddd, 1H)
JH5,F6 = 10.9
JH5,F4 = 8.3
–126.9 (dd, 1F)
JF6,H5 = 10.9
JF6,H3 ꢂ 2
JF4,H3, JF4,H5 ꢂ 8
JH3,H5 = 2.7
JH3,F6 = 2.1
JH5,H3 = 2.8
7.41 (dd, 1H)
JH3,F4 = 9.5
JH3,F5 = 8.4
–150.6 (ddd, 1F)
JF4,F5 = 21.0
JF4,H3 = 9.5
–137.7 (ddd, 1F)
JF5,F4 = 21.0
6.54 (dd, 1H)
JF6,F5 = 11.8
JH6,F4 ꢂ 7
JF5,H6 = 11.8
JF5,H3 = 8.4
JF4,H6 = 7.1
–110.2 (qd, 1F)
JF3,CF3 = 21.5
JF3,F6 = 9.7
–56.4 (dd, 3F)
–139.6 (dq, 1F)
–161.7 (dd, 1F)
JF6,F5 = 20.0
JF6,F3 = 9.7
JCF3,F3, JCF3,F5 ꢂ 21.5
JF5,CF3, JF5,F6 ꢂ 21.5
DMF at 50 8C for 8 h [25]. We found out that 2-bromo-3,5,6-
trifluoro-4-(trifluoromethyl)aniline (5) (synthesized by bromina-
tion of 1a) remained intact after exposing with alkyne 3f,
Pd(PPh3)2Cl2, CuI and Et3N in DMF at 90 8C for 7 h (19F NMR
data). Matching this result with the above literature data, one may
infer that the simultaneous fluorine implacement in the 3- and 5-
positions and fluorine substitution by a trifluoromethyl group in
the 4-position retard the Sonogashira coupling crucially. Howev-
er, basing on the current notion of the mechanism of this reaction
[45], the increased electron withdrawing substitution should
benefit the reaction. Thus, it turns out that only an electron-
donating effect of the F5 atom is responsible for the retardation,
but a special study is necessary for the firm conclusion.
Being potential precursors for corresponding indoles with
unsubstituted heterocyclic moiety, polyfluorinated 2-ethynylani-
lines are of principal importance, to obtain which anilines 4a–e,f
are likely appropriate starting materials. In this connection,
anilines 4bf and 4df were shown to smoothly afford 2-ethynyl-
tetrafluoroaniline (4bj) and known [25] 2-ethynyl-4,6-difluoroani-
line (4dj) in the 71 and 78% isolated yields, accordingly, upon
interaction with KOH in boiling benzene (the conditions are similar
to those used for preparation of 2-ethynylanthraquinone [46])
(Scheme 1).
intensity, shifted to low field by DdF 23.0, 3.0, 1.6 and 4.3 ppm,
from the similar signals of the starting aniline 1b (dF ꢀ142.5 (F3),
ꢀ174.0 (F4), ꢀ159.2 (F5) and ꢀ163.5 (F6) ppm), respectively. These
DdF values are characteristic for all pairs of anilines 1a–e–2a–e,
being in good conformity with those between pentafluorobenzene
and iodopentafluorobenzene [48]. Besides, the F3 DdF value
between anilines 2a and 5 (ꢀ15.0 ppm) is close to the ortho-F
DdF value (ꢀ13.4 ppm) between iodo- and bromo-pentafluoro-
benzene [48] (the negative DdF values correspond to a high-field
shift).
The 19F and 1H NMR spectral data of polyfluorinated 2-
ethynylanilines are presented in Table 4. Four equally intensive
signals observable in a 19F NMR spectrum of aniline 4bg are shifted
from their counterparts of aniline 2b by ꢀ17.7 for ortho, ꢀ0.5 and
ꢀ1.6 for meta and 1.9 ppm for para positions to the site of iodine
atom replacement by an alkynyl radical. These DdF values are
typical for all pairs of the respective ortho-iodo- and -alkynyla-
nilines and correspond to those between iodo- and ethynylpenta-
fluorobenzene [48], the signal spin-coupling structures being
virtually identical. Moreover, the 19F NMR spectra of 4e,f–i
coincide practically with that of 4,5-difluoro-2-[2-(trimethylsily-
l)ethynyl]aniline [34].
The 13C NMR spectral data of polyfluorinated 2-halo- and 2-
alkynylanilines are given in Table 5. The signals are assigned with
taking into account the 13C NMR data reported for pentafluor-
ophenylethynylbenzene and its halogen derivatives [49], keeping
2.3. Spectral data
The structures of all compounds obtained for the first time are
obvious enough from their synthesis and corroborated by their 19F,
1H and 13C NMR and IR characteristics. The 19F and 1H NMR
spectral data of polyfluorinated 2-haloanilines are presented in
Table 3. The observed 19F NMR chemical shifts and spin coupling
constants are fully consistent with their structures and typical for
polyfluorinated benzene derivatives [47]. For example, in the 19F
NMR spectrum of aniline 2b observed are four signals of equal
in mind that absolute JC–F values change in a sequence
1JC,F ꢁ JC,F > 3JC,F > 4JC,F [50]. The 13C NMR characteristics of
anilines 4d,f–i and 4e,f–i are reasonably close with those of 2-
ethynyl-4,6-difluoroaniline [25] and 2-[2-(trimethylsilyl)ethynyl]-
4,5-difluoroaniline [34]. Besides, the assignments of carbons of the
2
1
C–F fragments are confirmed by comparing the respective JC,F
values with those observed in satellite signals of the corresponding
fluorine resonances in the 19F NMR spectra. To assign ethynyl

102
L.V. Politanskaya, I.P. Chuikov / Journal of Fluorine Chemistry 135 (2012) 97–107
Table 4
1H and 19F NMR chemical shifts (ppm) and coupling constants (Hz) for anilines 4a–e,f–j (CDCl3).
Compound
NH2
R3
R4
R5
R6
Others
4af
4.84
ꢀ114.5 (dq, 1F)
JF3,CF3 = 21.6
JF3,F6 = 11.2
ꢀ56.4 (dd, 3F)
ꢀ137.5 (dq, 1F)
ꢀ164.9 (dd, 1F)
JF6,F5 = 20.2
1.63 (s, 6H, CH3)
2.52 (s, 1H, OH)
(s, 2H)
JCF3,F3, JCF3,F5 ꢂ 21
JF5,CF3, JF5,F6 ꢂ 21
JF6,F3 = 11.2
4ag
4.74
ꢀ115.5 (dq, 1F)
JF3,CF3 = 21.5
JF3,F6 = 11.2
ꢀ56.4 (dd, 3F)
ꢀ139.0 (dq, 1F)
ꢀ165.3 (dd, 1F)
JF6,F5 = 20.3
0.94 (t, 3H, CH3)
JH,H =7.2
(s, 2H)
JCF3,F3, JCF3,F5 ꢂ 21
JF5,CF3, JF5,F6 ꢂ 21
JF6,F3 = 11.2
1.47 (m, 2H, CH2CH3)
1.61 (m, 2H, CH2CH2CH3)
2.49 (t, 2H (CH2C(C)
JH,H =6.8
4ah
4ai
3.91
ꢀ114.3 (dq, 1F)
JF3,CF3 = 21.6
JF3,F6 = 11.1
ꢀ56.0 (dd, 3F)
ꢀ138.1 (dq, 1F)
ꢀ164.7 (dd, 1F)
JF6,F5 = 20.1
7.18–7.27 (m, 3H, Ph)
7.40–7.45 (m, 2H, Ph)
(s, 2H)
JCF3,F3, JCF3,F5 ꢂ 21
JF5,CF3, JF5,F6 ꢂ 21
JF6,F3 = 11.3
4.93
ꢀ111.3 (dq, 1F)
JF3,CF3 = 21.6
JF3,F6 = 11.3
ꢀ53.4 (dd, 3F)
ꢀ134.4 (dq, 1F)
ꢀ162.1 (dd, 1F)
JF6,F5 = 20.1
1.54–1.83 (m, 6=, E=2E=2E=2)
3.54 (m, 1H, ?E=2), 3.87 (m, 1H, ?E=2),
4.53 (s, 2H, CH2C(C)
(s, 2H)
JCF3,F3, JCF3,F5 ꢂ 21
JF5,CF3, JF5,F6 ꢂ 21
JF6,F3 = 11.3
4.85 (m, 1H, CH)
4bf
4.26
ꢀ139.3 (ddd, 1F)
JF3,F4 = 22.0
JF3,F6 = 9.7
ꢀ174.1 (ddd, 1F)
JF4,F3, JF4,F5 ꢂ 22
JF4,F6 =5.5
ꢀ157.0 (ddd, 1F)
JF5,F6, JF5,F4 ꢂ 21
JF5,F3 = 3.0
ꢀ163.3 (ddd, 1F)
JF6,F5 = 20.4
JF6,F3 = 9.7
1.63 (s, 6H, CH3)
2.52 (s, 1H, OH)
(s, 2H)
JF6,F5 = 3.0
JF6,F4 = 5.5
4bg
4.19
ꢀ137.2 (ddd, 1F)
JF3,F4 = 22.1
ꢀ171.5 (ddd, 1F)
JF4,F3, JF4,F5 ꢂ 22
JF4,F6 =5.6
ꢀ155.7 (ddd, 1F)
JF5,F4, JF5,F6 ꢂ 21
ꢀ160.7 (ddd, 1F)
JF6,F5 = 20.4
JF6,F3 = 9.5
0.93 (t, 3H, CH3)
JH,H =7.3
(s, 2H)
JF3,F6 = 9.5
1.46 (m, 2H, CH2CH3)
1.60 (m, 2H, CH2CH2CH3)
2.49 (t, 2H, CH2C(C)
JH,H =6.9
JF6,F4 = 5.6
4bh
4bi
4bj
4cf
4cg
4.43
ꢀ138.9 (ddd, 1F)
JF3,F4 = 22.2
JF3,F6 = 9.6
ꢀ174.0 (ddd, 1F)
JF4,F3, JF4,F5 ꢂ 22
JF4,F6 =5.5
ꢀ157.0 (ddd, 1F)
JF5,F4, JF5,F6 ꢂ 21
JF5,F3 = 2.8
ꢀ163.3 (ddd, 1F)
JF6,F5 = 20.4
JF6,F3 = 9.6
7.34–7.39 (m, 3H, Ph)
7.51–7.56 (m, 2H, Ph)
(s, 2H)
JF3,F5 = 2.8
JF6,F4 = 5.5
4.34
ꢀ139.0 (ddd, 1F)
JF3,F4 = 22.0
JF3,F6 = 9.6
ꢀ174.4 (ddd, 1F)
JF4,F3, JF4,F5 ꢂ 22
JF4,F6 =5.5
ꢀ156.9 (ddd, 1F)
JF5,F6, JF5,F4 ꢂ 21
JF5,F3 = 2.7
ꢀ163.5 (ddd, 1F)
JF6,F5 = 20.3
JF6,F3 = 9.6
1.51–1.83 (m, 6=, E=2E=2E=2)
3.54 (m, 1H, ?E=2), 3.86 (m, 1H, ?E=2),
4.53 (s, 2H, CH2C(C)
(s, 2H)
JF3,F5 = 2.7
JF6,F4 = 5.5
4.85 (m, 1H, CH)
4.32
ꢀ139.1 (ddd, 1F)
JF3,F4 = 22.0
JF3,F6 = 9.6
ꢀ174.2 (ddd, 1F)
JF4,F3, JF4,F5 ꢂ 22
JF4,F6 =5.5
ꢀ156.3 (ddd, 1F)
JF5,F6, JF5,F4 ꢂ 21
JF5,F3 = 3.1
ꢀ163.3 (ddd, 1F)
JF6,F5 = 20.0
JF6,F3 = 9.6
3.63 (s, 1H, C(CH)
(s, 2H)
JF3,F5 = 3.1
JF6,F4 = 5.5
4.14
ꢀ141.5 (ddd, 1F)
JF3,F4 = 21.3
ꢀ151.1 (ddd, 1F)
JF4,F3 =21.8
JF4,H5 = 10.0
JF4,F6 =2.2
6.82 (ddd, 1H)
JH5,F4, J H5,F6 ꢂ 10
JH5,F3 = 7.1
ꢀ138.1 (ddd, 1F)
JF6,F3 = 13.1
1.62 (s, 6H, CH3)
2.74 (s, 1H, OH)
(s, 2H)
JF3,F6 = 13.4
JF6,H5 = 11.0
JF6,H4 = 2.2
JF3,H5 = 7.1
4.06
ꢀ142.2 (ddd, 1F)
JF3,F4 = 21.3
ꢀ151.2 (ddd, 1F)
JF4,F3 =21.9
JF4,H5 = 9.9
6.79 (ddd, 1H)
JH5,F4, JH5,F6 ꢂ 10
JH5,F3 = 7.1
ꢀ138.5 (ddd, 1F)
JF6,F3 = 13.4
0.93 (t, 3H, CH3)
JH,H =7.3
(s, 2H)
JF3,F6 = 13.4
JF6,H5 = 10.6
JF6,H4 = 2.5
1.47 (m, 2H, CH2CH3)
1.61 (m, 2H, CH2CH2CH3)
2.50 (t, 2H, CH2C(C)
JH,H =7.0
JF3,H5 = 7.1
JF4,F6 =2.5
4ch
4ci
4.25
ꢀ140.7 (ddd, 1F)
JF3,F4 = 21.7
JF3,F6 = 13.4
JF3,H5 = 7.0
ꢀ150.5 (ddd, 1F)
JF4,F3 =21.9
JF4,H5 = 10.0
JF4,F6 =2.5
6.92 (ddd, 1H)
JH5,F4, JH5,F6 ꢂ 10
JH5,F3 = 7.0
ꢀ137.7 (ddd, 1F)
JF6,F3 = 13.4
JF6,H5 = 10.5
JF6,F4 = 2.5
7.40–7.42 (m, 3H, Ph)
7.58–7.61 (m, 2H, Ph)
(s, 2H)
4.19
ꢀ141.2 (ddd, 1F)
JF3,F4 = 21.2
ꢀ151.2 (ddd, 1F)
JF4,F3 =21.8
JF4,H5 = 10.0
JF4,F6 =2.4
6.84 (ddd, 1H)
JH5,F4, JH5,F6 ꢂ 10
JH5,F3 = 7.1
ꢀ138.3 (ddd, 1F)
JF6,F3 = 13.4
JF6,H5 = 10.9
JF6,F4 = 2.4
1.52–1.88 (m, 6=, E=2E=2E=2)
3.55 (m, 1H, ?E=2), 3.87 (m, 1H, ?E=2),
4.55 (s, 2H, CH2C(C)
(s, 2H)
JF3,F6 = 13.4
JF3,H5 = 7.1
4.87 (m, 1H, CH)
4df
4.07
6.68–6.75 (m, 1H)
ꢀ126.0 (dd, 1F)
JF4,H3, JF4,H5 ꢂ 8
6.68–6.75 (m, 1H)
ꢀ131.3 (d, 1F)
JF6,H5 ꢂ 10
1.59 (s, 6H, CH3)
3.08 (s, 1H, OH)
(s, 2H)

L.V. Politanskaya, I.P. Chuikov / Journal of Fluorine Chemistry 135 (2012) 97–107
103
Table 4 (Continued )
Compound
NH2
R3
R4
R5
R6
Others
4dg
4.00
6.76 (dm, 1H)
ꢀ125.5 (dd, 1F)
JF4,H3, JF4,H5 ꢂ 9
6.70 (ddd, 1H)
JH5,H6 ꢂ 11
JH5,F4 ꢂ 9
ꢀ130.7 (d, 1F)
JF6,H5 = 10.8
0.93 (t, 3H, CH3)
JH,H = 7.3
(s, 2H)
JH3,F4 = 8.9
1.46 (m, 2H, CH2CH3)
1.58 (m, 2H, CH2CH2CH3)
2.45 (t, 2H, CH2C(C)
JH,H = 7.1
JH5,H3 ꢂ 3
4dh
4di
4.18
6.93 (dm, 1H)
JH3,F4 = 8.8
ꢀ126.0 (dd, 1F)
JF4,H3, JF4,H5 ꢂ 9
6.81 (ddd, 1H)
JH5,H6 = 11.0
JH5,F4 = 8.6
ꢀ131.3 (d, 1F)
JF6,H5 = 10.8
7.38–7.39 (m, 3H, Ph)
7.54–7.57 (m, 2H, Ph)
(s, 2H)
JH3,F5 = 2.8
JH5,H3 = 2.8
4.09
6.74–6.9 (dm, 1H)
ꢀ126.4 (dd, 1F)
JF4,H3, JF4,H5 ꢂ 8
6.74–6.79 (ddd, 1H)
JH5,H6 ꢂ 11
ꢀ131.5 (d, 1F)
JF6,H5 = 10.7
1.51–1.83 (m, 6=, E=2E=2E=2)
3.56 (m, 1H, ?E=2), 3.86 (m, 1H, ?E=2),
4.51 (s, 2H, CH2C(C)
(s, 2H)
JH3,F4 ꢂ 8
JH5,F4 ꢂ 9
JH5,H3 ꢂ 3
4.85 (m, 1H, CH)
4dj
4ef
4.15
6.75–6.87 (m, 1H)
ꢀ126.0 (dd, 1F)
JF4,H3, JF4,H5 ꢂ 9
6.75–6.87 (m, 1H)
ꢀ131.0 (d, 1F)
JF6,H5 = 10.8
3.45 (s, 1H, C(CH)
(s, 2H)
4.17
7.00 (dd, 1H)
JH3,F4 = 10.4
JH3,F5 = 8.7
ꢀ152.6 (ddd, 1F)
JF4,F5 = 22.1
JF4,F3 = 10.4
ꢀ135.6 (ddd, 1F)
JF5,F4 = 22.1
6.45 (dd, 1H)
JH6,F5 = 11.8
JH6,F4 = 7.2
1.59 (s, 6H, CH3)
2.71 (s, 1H, OH)
(s, 2H)
JF5,H6 = 11.8
JF5,H3 = 8.7
JF4,H6 = 7.2
4eg
4.10
6.99 (dd, 1H)
JH3,F4 = 10.7
JH3,F5 = 8.7
ꢀ153.2 (ddd, 1F)
JF4,F5 = 22.3
ꢀ137.3 (ddd, 1F)
JF5,F4 = 22.3
6.43 (dd, 1H)
JH6,F5 = 11.8
JH6,F4 = 7.2
0.92 (t, 3H, CH3)
JH,H = 7.3
(s, 2H)
JF4,H3 = 10.7
JF4,H6 = 7.2
JF5,H6 = 11.8
JF5,H3 = 8.7
1.47 (m, 2H, CH2CH3)
1.57 (m, 2H, CH2CH2CH3)
2.42 (t, 2H, CH2C(C)
JH,H = 6.8
4eh
4ei
4.30
7.21 (dd, 1H)
JH3,F4 = 10.5
JH3,F5 = 8.8
ꢀ152.5 (ddd, 1F)
JF4,H5 = 22.1
JF4,H3 = 10.5
JF4,H6 = 7.1
ꢀ135.4 (ddd, 1F)
JF5,F4 = 22.1
6.54 (dd, 1H)
JH6,F5 = 11.8
JH6,F4 = 7.1
7.40–7.42 (m, 3H, Ph)
7.56–7.59 (m, 2H, Ph)
(s, 2H)
JF5,H6 = 11.8
JF5,H3 = 8.8
4.19
7.04 (dd, 1H)
JH3,F4 = 10.5
JH3,F5 = 8.7
ꢀ152.8 (ddd, 1F)
JF4,H5 = 22.2
JF4,H3 = 10.5
JF4,H6 = 7.0
ꢀ135.3 (ddd, 1F)
JF5,F4 = 22.2
6.43 (dd, 1H)
JH6,F5 = 11.8
JH6,F4 = 7.0
1.52–1.83 (m, 6=, E=2E=2E=2)
3.54 (m, 1H, ?E=2), 3.86
(m, 1H, ?E=2), 4.48 (s, 2H, CH2C(C)
4.85 (m, 1H, CH)
(s, 2H)
JF5,H6 = 11.8
JF5,H3 = 8.7
carbons of 4a–e,f–j, informative was that in the 13C spectrum of
4bj, registered without C–H spin decoupling, the C8 exhibits a
doublet with 1JC8,H = 255.6 Hz, whereas the C7 signal appears as a
pentafluoroiodobenzene (66.1 ppm) [51]. Interestingly, a depen-
dence is observed of the ethynyl C values onsubstitution both inthe
fluorinated benzene ringand atthe ethynyl -C-atom. Thus, ingoing
from anilines 4a–e,f–i, containing fluorine ortho to the ethynyl
fragment, to 4d–e,f–i, having no substituent at the 3-position, the
d
b
doublet with 2JC7,H = 50.6 Hz. Accordingly, the signals at
d
C = 67–
84 ppm in the 13C NMR spectra of 4a–e,f–j are assigned to C7
adjacent to the polyfluorinated benzene ring. Only the J values
most structurally informative for the 13C signals assignment are
shown in Table 5.
two ethynyl signals approach eachother asa result of the
a-C drift to
a high field and of the -C signals – to a low field, both moving
b
towards the ethynyl dC values reported for 2-ethynyl-4,6-difluor-
oaniline [25] and nonfluorinated tolanes [52,53]. The similar takes
Thatlow-fieldlocation ofthe C2 resonances of2aand2biscaused
by polyfluorination of the benzene ring is illustrated by the
respective values for 1-fluoro-4-iodobenzene (87.1 ppm) and
place in going from anilines with
b-substituents CMe2OH (f) and n-
Bu (g) to those with -substituents Ph (h) and CH2OTHP (i).
b
Table 5
13C NMR chemical shifts (ppm) and coupling constants (Hz) for anilines 2a–e, 4a–e,f–j and 5 (CDCl3).
C1
C2
C3
C4
C5
C6
C7
C8
Others
2a
2b
2c
141.2
65.5
154.7
96.7
148.3
134.5
121.5 (CF3)
1JCF3,F = 272.7
2JC1,F6 = 11.1
2JC2,F3 = 32.1
1JC3,F3 = 248.7
3JC3,CF3 = 1.6
2JC4,CF3 = 34.6
2JC4,F3 = 19.6
2JC4,F5 = 12.5
1JC5,F5 = 257.2
2JC5,F6 = 13.5
3JC5,CF3 = 1.6
1JC6,F6 = 241.8
2JC6,F5 = 15.5
133.0
2JC1,F6 = 11.9
65.2
2JC2,F3 = 27.2
147.2
132.3
141.0
135.2
1JC3,F3 = 239.8
2JC3,F4 = 11.5
1JC4,F4 = 246.0
2JC4,F3 = 19.3
2JC4,F5 = 13.5
1JC5,F5 = 250.0
2JC5,F4 = 14.1
2JC5,F6 = 13.4
1JC6,F6 = 242.4
2JC6,F5 = 12.8
133.2
72.9
146.9
141.1
105.1
144.5

104
L.V. Politanskaya, I.P. Chuikov / Journal of Fluorine Chemistry 135 (2012) 97–107
Table 5 (Continued )
C1
C2
C3
C4
C5
C6
C7
C8
Others
2JC1,F6 = 15.2
2JC2,F3 = 26.6
1JC3,F3 = 239.5;
2JC3,F4 = 14.2
1JC4,F4 = 243.6
2JC4,F3 = 16.7
3JC4,F6 = 11.8
2JC5,F4 = 25.0
2JC5,F6 = 22.2
1JC6,F6 = 241.7
3JC6,F4 = 9.6
2d
2e
5
133.0
82.3
120.3
154.4
104.2
148.9
2JC1,F6 = 14.0
3JC2,F4 = 10.5
2JC3,F4 = 24.2
1JC4,F4 = 242.4
3JC4,F6 = 11.9
2JC5,F4 = 26.3
2JC5,F6 = 23.5
1JC6,F6 = 245.9
3JC6,F4 = 12.0
144.0
3JC1,F5 = 8.7
74.9
3JC2,F4 = 6.5
126.5
2JC3,F4 = 20.0
143.1
150.9
102.6
2JC6,F5 = 21.0
1JC4,F4 = 243.0
2JC4,F5 = 13.5
1JC5,F5 = 246.6
2JC5,F4 = 13.3
138.7
2JC1,F6 = 11.9
91.8
2JC2,F3 = 26.4
152.8
97.2
147.4
135.5
121.7 (CF3)
1JCF3,F = 273.0
1JC3,F3 = 252.0
3JC3,CF3 = 1.9
2JC4,CF3 = 34.7
2JC4,F3 = 17.7
2JC4,F5 = 12.6
1JC5,F5 = 257.2
2JC5,F6 = 13.5
3JC5,CF3 = 1.8
1JC6,F6 = 241.0
2JC6,F5 = 15.6
4af
141.1
94.3
156.3
96.8
148.0
135.4
69.6
67.8
106.1
103.0
31.4 (CH3)
65.9 (COH)
121.7 (CF3)
1JCF3,F = 272.4
2JC1,F6 = 11.1
2JC2,F3 = 21.8
1JC3,F3 = 256.8
3JC3,CF3 ꢂ 2
2JC4,CF3 = 34.7
2JC4,F3 = 16.3
2JC4,F5 = 12.6
1JC5,F5 = 259.2
2JC5,F6 = 13.2
3JC5,CF3 ꢂ 2
1JC6,F6 = 238.4
2JC6,F5 = 15.2
4ag
141.0
2JC1,F6 = 11.4
95.8
2JC2,F3 = 21.8
156.3
96.8
147.5
135.5
13.6 (CH3)
19.4 (CH2)
22.0 (CH2)
30.6 (CH2)
121.8 (CF3)
1JCF3,F = 272.6
1JC3,F3 = 255.8
3JC3,CF3 ꢂ 2
2JC4,CF3 = 34.7
2JC4,F3 = 16.3
2JC4,F5 = 12.6
1JC5,F5 = 258.1
2JC5,F6 = 15.0
3JC5,CF3 ꢂ 2
1JC6,F6 = 237.7
2JC6,F5 = 15.3
4ah
140.9
95.2
156.2
97.1
148.1
135.5
76.1
73.2
101.0
121.7 (CF3)
1JCF3,F = 272.8
121.8 (Ph)
128.6 (Ph)
129.3 (Ph)
131.7 (Ph)
2JC1,F6 = 11.7
2JC2,F3 = 21.7
1JC3,F3 = 257.1
3JC3,CF3 ꢂ 2
2JC4,CF3 = 34.7
2JC4,F3 = 16.3
2JC4,F5 = 12.6
1JC5,F5 = 258.8
2JC5,F6 = 13.1
3JC5,CF3 ꢂ 2
1JC6,F6 = 238.5
2JC6,F5 = 15.2
4ai
141.8
2JC1,F6 = 11.7
94.3
2JC2,F3 = 21.9
156.5
96.5
148.2
135.4
97.5
19.0 (CH2)
25.3 (CH2)
30.3 (CH2)
55.2 (CH2)
62.3 (CH2)
97.8 (CH)
1JC3,F3 = 257.3
3JC3,CF3 ꢂ 2
2JC4,CF3 = 34.7
2JC4,F3 = 16.3
2JC4,F5 = 12.6
1JC5,F5 = 259.2
2JC5,F6 = 13.4
3JC5,CF3 ꢂ 2
1JC6,F6 = 238.2
2JC6,F5 = 15.2
121.7 (CF3)
1JCF3,F = 272.3
4bf
4bg
4bh
4bi
133.4
93.8
147.8
132.7
141.5
136.0
69.9
68.1
76.4
73.5
105.8
102.9
100.7
97.4
31.4 (CH3)
65.9 (COH)
2JC1,F6 = 11.5
2JC2,F3 = 17.5
1JC3,F3 = 247.7
2JC3,F4 = 11.2
1JC4,F4 = 242.1
2JC4,F3 = 16.3
2JC4,F5 = 13.4
1JC5,F5 = 252.0
2JC5,F4, 2JC5,F6 ꢂ 14
1JC6,F6 = 238.8
2JC6,F5 = 12.6
133.2
2JC1,F6 = 11.5
95.2
2JC2,F3 = 17.7
148.0
132.8
140.9
136.1
13.5 (CH3)
19.5 (CH2)
22.0 (CH2)
30.6 (CH2)
1JC3,F3 = 246.5
2JC3,F4 = 11.1
1JC4,F4 = 241.6
2JC4,F3 = 16.7
2JC4,F5 = 13.3
1JC5,F5 = 250.8
2JC5,F4, 2JC5,F6 ꢂ 14
1JC6,F6 = 238.2
2JC6,F5 = 12.7
133.2
2JC1,F6 = 11.8
94.4
2JC2,F3 = 17.7
147.6
132.7
141.3
135.9
121.9 (Ph)
128.4 (Ph)
129.1 (Ph)
131.5 (Ph)
1JC3,F3 = 247.9
2JC3,F4 = 11.1
1JC4,F4 = 242.3
2JC4,F3 = 16.6
2JC4,F5 = 13.5
1JC5,F5 = 252.2
2JC5,F4, 2JC5,F6 ꢂ 14
1JC6,F6 = 236.3
2JC6,F5 = 12.3
134.0
2JC1,F6 = 11.6
93.6
2JC2,F3 = 17.7
148.0
132.5
141.6
136.0
19.0 (CH2)
25.3 (CH2)
30.3 (CH2)
55.1 (CH2)
62.3 (CH2)
97.6 (CH)
1JC3,F3 = 248.1
2JC3,F4 = 11.1
1JC4,F4 = 241.8
2JC4,F3 = 16.6
2JC4,F5 = 13.5
1JC5,F5 = 252.3
2JC5,F4, 2JC5,F6 ꢂ 14
1JC6,F6 = 238.8
2JC6,F5 = 12.8
4bj
4cf
4cg
4ch
134.5
93.4
148.5
132.8
142.0
136.2
71.6
89.0
2JC1,F6 = 11.7
2JC2,F3 = 17.5
1JC3,F3 = 249.0
2JC3,F4 = 11.2
1JC4,F4 = 242.4
2JC4,F3 = 16.4
2JC4,F5 = 13.8
1JC5,F5 = 253.0
2JC5,F4, 2JC5,F6 ꢂ 14
1JC6,F6 = 239.0
2JC6,F5 = 12.6
2JC7,H = 50.6
1JC8,H = 255.6
133.3
2JC1,F6 = 15.1
99.5
2JC2,F3 = 17.5
147.0
141.1
105.4
145.3
70.9
69.3
77.9
106.1
103.2
100.9
31.4 (CH3)
65.8 (COH)
1JC3,F3 = 245.8
2JC3,F4 = 13.7
1JC4,F4 = 239.2
2JC4,F3 = 13.9
2JC4,F5 = 12.7
2JC5,F4 = 24.4
2JC5,F6 = 22.3
1JC6,F6 = 238.0
3JC6,F4 = 10.4
133.1
2JC1,F6 = 14.9
101.0
2JC2,F3 = 17.6
147.4
141.3
104.5
2JC5,F4, 2JC5,F6 ꢂ 23
145.4
13.6 (CH3)
19.5 (CH2)
22.0 (CH2)
30.6 (CH2)
1JC3,F3 = 245.3
2JC3,F4 = 13.7
1JC4,F4 = 238.9
2JC4,F3, 2JC4,F5 ꢂ 14
1JC6,F6 = 237.2
3JC6,F4 = 10.5
133.4
100.2
147.2
141.5
105.5
145.5
122.4 (Ph)

L.V. Politanskaya, I.P. Chuikov / Journal of Fluorine Chemistry 135 (2012) 97–107
105
Table 5 (Continued )
C1
C2
C3
C4
C5
C6
C7
C8
Others
2JC1,F6 = 15.7
2JC2,F3 = 17.5
1JC3,F3 = 246.8
2JC3,F4 = 13.6
1JC4,F4 = 239.3
2JC4,F3, 2JC4,F5 ꢂ 13
2JC5,F4, 2JC5,F6 ꢂ 23
1JC6,F6 = 237.8
3JC6,F4 = 10.5
128.7 (Ph)
129.9 (Ph)
131.9 (Ph)
4ci
133.8
2JC1,F6 = 15.1
99.4
2JC2,F3 = 17.7
147.4
141.0
105.6
2JC5,F4, 2JC5,F6 ꢂ 23
145.2
74.6
97.6
19.1 (CH2)
25.3 (CH2)
30.3 (CH2)
55.0 (CH2)
62.2 (CH2)
97.5 (CH)
1JC3,F3 = 246.9
2JC3,F4 = 13.8
1JC4,F4 = 239.2
2JC4,F3 = 13.6
2JC4,F5 = 12.4
1JC6,F6 = 237.8
3JC6,F4 = 10.4
4df
133.0
109.4
113.3
153.8
104.6
150.6
76.8
75.3
101.3
97.9
31.5 (CH3)
65.6 (COH)
2JC1,F6 = 13.7
3JC2,F4 = 11.0
2JC3,F4 = 23.4
1JC4,F4 = 237.9
3JC4,F6 = 12.3
2JC5,F4 = 26.8
2JC5,F6 = 22.9
1JC6,F6 = 241.6
3JC6,F4 = 12.7
4dg
132.9
2JC1,F6 = 13.5
110.9
3JC2,F4 = 11.0
113.3
2JC3,F4 = 23.2
153.9
103.8
150.5
13.6 (CH3)
19.3 (CH2)
22.1 (CH2)
30.8 (CH2)
1JC4,F4 = 237.4
3JC4,F6 = 12.5
2JC5,F4 = 26.8
2JC5,F6 = 22.9
1JC6,F6 = 241.0
3JC6,F4 = 12.9
4dh
4di
133.2
109.8
113.3
153.9
104.7
150.6
83.8
80.5
96.4
92.5
122.5 (Ph)
128.5 (Ph)
128.9 (Ph)
131.6 (Ph)
2JC1,F6 = 13.7
3JC2,F4 = 11.0
2JC3,F4 = 23.3
1JC4,F4 = 237.9
3JC4,F6 = 12.4
2JC5,F4 = 26.9
2JC5,F6 = 22.8
1JC6,F6 = 241.6
3JC6,F4 = 12.7
133.7
2JC1,F6 = 13.8
109.0
3JC2,F4 = 10.9
113.5
2JC3,F4 = 23.3
153.6
104.9
150.4
19.0 (CH2)
25.3 (CH2)
30.3 (CH2)
54.9 (CH2)
62.2 (CH2)
97.3 (CH)
1JC4,F4 = 237.8
3JC4,F6 = 12.3
2JC5,F4 = 26.8
2JC5,F6 = 22.8
1JC6,F6 = 241.6
3JC6,F4 = 12.7
4ef
144.9
102.9
120.0
142.8
151.2
103.0
84.0
75.3
99.7
96.3
31.6 (CH3)
65.7 (COH)
3JC1,F5 = 9.4
3JC2,F4 = 7.0
2JC3,F4 = 19.0
1JC4,F4 = 238.1
2JC4,F5 = 13.4
1JC5,F5 = 249.1
2JC5,F4 = 13.7
2JC6,F5 = 20.9
4eg
144.8
104.5
119.8
142.7
150.6
102.7
13.6 (CH3)
3JC1,F5 = 9.1
3JC2,F4 = 6.9
2JC3,F4 = 18.6
1JC4,F4 = 237.4
2JC4,F5 = 13.5
1JC5,F5 = 247.6
2JC5,F4 = 13.7
2JC6,F5 = 20.8
19.2 (CH2)
22.1 (CH2)
30.9 (CH2)
4eh
4ei
144.9
103.1
119.5
142.5
151.0
102.6
83.8
80.8
94.7
91.0
122.4 (Ph)
128.2 (Ph)
128.3 (Ph)
131.2 (Ph)
3JC1,F5 = 9.4
3JC2,F4 = 7.3
2JC3,F4 = 18.9
1JC4,F4 = 237.9
2JC4,F5 = 13.6
1JC5,F5 = 249.1
2JC5,F4 = 13.8
2JC6,F5 = 20.9
145.5
3JC1,F5 = 9.4
102.5
3JC2,F4 = 7.3
120.2
2JC3,F4 = 18.9
142.7
151.4
102.8
2JC6,F5 = 20.9
19.1 (CH2)
25.3 (CH2)
30.3 (CH2)
54.9 (CH2)
62.2 (CH2)
97.2 (CH)
1JC4,F4 = 238.0
2JC4,F5 = 13.5
1JC5,F5 = 249.3
2JC5,F4 = 13.8
In the IR spectra of all anilines synthesized the valence
vibrations of the N–H (3354–3496 cmꢀ1
and C(C (2206–
2235 cmꢀ1) bonds are observed. Characteristic for compound
4bj are the ethynyl C–H vibration at 3304 cmꢀ1 and the high-
frequency shift (ꢃ100 cmꢀ1) of the C(C band from that of anilines
4a–e,f–i (cf [46]).
CHCl3
and C6F6
(dH 7.24 ppm), CDCl3 (dC 76.9 ppm) as internal references
)
(
d
F = ꢀ163.0 ppm) as an external reference. 13C NMR
spectra were registered with C–H spin decoupling, while the
another is not stated.
Masses of molecular ions were determined by HRMS on a DFS
Thermo scientific instrument (EI, 70 eV), or by Hybrid Quadrupole
Time of Flight mass spectrometer (microTOF-Q, Bruker) equipped
with Atmospheric Pressure Chemical Ionization (APCI) and
Atmospheric Pressure Electrostatic Spray Ionization (API-ES).
GC–MS was performed in a Hewlett–Packard instrument with a
HP 5890 Series II gas chromatograph and HP 5971 (EI, 70 eV) mass-
selective detector using a HP5MS capillary column (30 mm ꢄ
0.25 mm ꢄ 0.25 mm); the carrier gas was He et 1 mL/min. IR
spectra were recorded with a Bruker V-22 spectrometer. The
starting 2-(prop-2-in-1-yloxy)oxane 3i [54] and Pd(PPh3)2Cl2 [55]
were prepared by the reported protocols. 3,4-Difluoroaniline, other
materials and solvents were of a commercial supply, the solvents
having been distilled. Sorbfil plates were used for products
isolation by TLC (eluent: hexane–EtOAc, 10 ꢅ 5: 1) as an oils.
According to 19F NMR data with calibration of peak intensities by
C6F6 as an internal standard the first synthesized compounds had
purity ꢆ95% (Table 6).
3. Conclusion
By means of the Pd-catalysed condensation of polyfluorinated
ortho-iodoanilines with terminal alkynes the corresponding ortho-
alkynylanilines – base building blocks for assembling polyfluor-
obenzoazaheterocycles and molecular design of their functional
derivatives were obtained.
4. Experimental
4.1. General
NMR spectra were recorded on a Bruker AV-300 (300.13 for 1H
and 282.37 MHz for 19F) and AV-400 (400.13 for 1H, 376.44 for 19
F
and 100.62 MHz for 13C) spectrometers in CDCl3 using residual

106
L.V. Politanskaya, I.P. Chuikov / Journal of Fluorine Chemistry 135 (2012) 97–107
Table 6
Exact values of molecular ion masses and IR data of anilines 2a–d and 4a–e,f–j.
Compound
m/z
Calcd for
[M]+ (calcd)
[M]+ (found)
IR spectra, v )
(Fmꢀ1
OH (C(C–H)
NH2
C(C
2a
[M]+
C7H2F6IN
340.9131
272.9257
254.9351
297.0583
295.0790
315.0477
353.0845
230.0587
245.0822
264.0442
303.0877
189.0196
229.0709
227.0916
248.0682
285.0971
211.0803
209.1011
229.0698
268.1144
211.0803
210.1089
228.0630
268.1144
340.9133
272.9258
254.9350
297.0584
295.0793
315.0475
353.0847
230.0586
245.0821
264.0440
303.0876
189.0200
229.0711
227.0915
248.0690
285.0968
211.0800
209.1016
229.0699
268.1132
211.0802
210.1085
228.0623
268.1141
3507, 3402
3480, 3383
3465, 3369
3411, 3358
3515, 3408
3511, 3405
3474, 3339
3355
2c
[M]+
C6H3F3IN
2d
[M]+
C6H4F2IN
4af
4ag
4ah
4ai
4bf
4bg
4bh
4bi
4bj
4cf
4cg
4ch
4ci
[M]+
C12H9F6NO
C13H11F6N
C15H7F6N
3609
3604
2232
2232
2214
2231
2227
2235
2211
2233
2112
2227
2230
2206
2231
2223
2229
2206
2229
2218
2225
2206
2223
[M]+
[M]+
[M]+
C15H13F6NO2
C11H8F4N
[M+H+ꢀH2O]+
[M]+
C12H11F4N
C14H6F4N
3496, 3396
3473, 3386
3470, 3354
3503, 3402
3359
[M–H+]–
[M]+
C14H13F4NO2
C8H3F4N
[M]+
3304 (C(CH)
3599
[M]+
C11H10F3NO
C12H12F3N
C14H9F3N
[M]+
3472, 3396
3473, 3392
3475, 3354
3350
[M+H+]+
[M]+
C14H14F3NO2
C11H11F2NO
C12H13F2N
C14H9F2N
4df
4dg
4dh
4di
4ef
4eg
4eh
4ei
[M]+
3568
3568
[M]+
3481, 3384
3476, 3386
3469, 3357
3408, 3301
3477, 3384
3452, 3361
3469, 3361
[M]+
[M+H+]+
[M]+
C14H16F2NO2
C11H11F2NO
C12H14F2N
C14H8F2N
[M+H+]+
[MꢀH+]–
[M+H+]+
C14H16F2NO2
4.2. Synthetic procedures
anilines 4a–e,f–i), and powdered KOH (0.078 g, 1.4 mmol) in
absolute benzene (8 mL) were refluxed with stirring for 40 min.
The mixture was cooled to r.t. and poured into a mixture of H2O
(30 mL) and CHCl3 (20 mL). The aqueous layer was extracted with
CHCl3 (2 ꢄ 30 mL), the collected organic solution was washed with
H2O (3 ꢄ 30 mL) and dried (MgSO4). Evoparation of the solvent and
chromatography (TLC) of the crude product (eluent: hexane–
EtOAc, 15:1 ! 15:1 ! 15:1, Rf = 0.46) gave aniline 4bj (0.093 g,
71% on 2b) as an oil.
4.2.1. 2-Iodo-3,5,6-trifluoro-4-(trifluoromethyl)aniline (2a). Method
I (typical procedure for anilines 2a–d).
To a stirred solution of aniline 1a (0.52 g, 2.4 mmol) in dioxane
(18 mL) at 70 8C were added 0.31
( (1.2 mmol) fine-ground iodine
and a solution of iodic acid (0.43 g, 2.4 mmol) in H2O (3 mL). The
reaction mixture was refluxed for 4 h, cooled to r.t., poored into
H2O (50 mL) and extracted with CHCl3 (3 ꢄ 30 mL). The extract
was washed with sat. Na2S2O3 (2 ꢄ 30 mL) and NaCl (30 mL)
solutions, then with H2O (30 mL), dried (MgSO4), and purified by
flash chromatography on Al2O3 to afford 2a (0.79 g, 97%) as an oil.
Method II. A solution of 2,3,5-trifluoro-4-(trifluoromethyl)ani-
line 1a (0.34 g, 1.57 mmol) in EtOH (3 mL) was added during
15 min to a stirred mixture of I2 (0.51 g, 2.0 mmol), Ag2SO4 (0.62 g,
2.0 mmol) and EtOH (10 mL). The mixture was boiled for 4 h,
filtered, solvent was evaporated. The residue was dissolved in
CHCl3 (40 mL), the solution was washed with sat. aq. solutions of
Na2S2O3 (2 ꢄ 30 mL) and NaCl (30 mL), then with H2O (30 mL),
dried (MgSO4), and purified by flash chromatography on Al2O3 to
afford 2a (0.49 g, 93%) as an oil.
4.2.4. 2-Bromo-3,5,6-trifluoro-4-(trifluoromethyl)aniline (5)
To a stirred solution of aniline 1a (2.0 g, 9.3 mmol) in glycial
AcOH (7 mL) were added powdered iron (0.07 g, 1.3 mmol) and
anhydrous AcONa (1.0 g, 12.1 mmol). The mixture was warmed to
45 8C and a solution of Br2 (2.7 g, 16.8 mmol) in AcOH (7 mL) was
dropwise added for 1 h. The mixture was stirred at 60 8C for 2 h,
then cooled to r.t. and decolorized by adding a sat. aq. solution of
Na2S2O3 and steam distilled. The distillate was extracted with
CHCl3 (3 ꢄ 50 mL), the extract was washed with H2O (50 mL), dried
(MgSO4), evaporated to afford the title aniline (2.3 g, 85%) as a
colorless solid. m.p.: 33–34 8C. IR (KBr): 3510 and 3414
(NH2) cmꢀ1. Anal. Calcd. for C7H2F6BrN: C, 28.60; H, 0.69, Br,
27.18; N, 4.76. Found: C, 28.42; H, 0.70; Br, 27.15; N, 4.72.
4.2.2. 2,3,4,5-Tetrafluoro-6-(hex-1-yn-1-yl)aniline (4bg) (typical
procedure for anilines 4a–e,f–i)
To a stirred mixture of aniline 2b (0.100 g, 0.344 mmol), hex-1-
yne 3g (0.084 g, 1.031 mmol) and Et3N (3 mL) under argon added
were Pd(PPh3)2Cl2 (0.010 g, 0.014 mmol), CuI (0.006 g, 0.031 mmol)
and, additionally,Et3N(3 mL). Stirringwascontinuedat70 8Cfor3 h,
the mixture was cooled to r.t., diluted by CHCl3 (10 mL) and poured
into a mixture of H2O (30 mL) and CHCl3 (20 mL). The aqueous layer
was extractedwithCHCl3 (2 ꢄ 30 mL), the collectedorganicsolution
was washed with H2O (3 ꢄ 30 mL) and dried (MgSO4). Evoparation
of the solvent and chromatography (TLC) of the crude product
(eluent: hexane–EtOAc, 10:1 ! 10:1 ! 10:1, Rf = 0.54) gave aniline
4bg (0.067 g, 80%) as an oil.
Acknowledgment
The authors thank Russian Foundation of Basic Research for
financial support (grant 09-03-00248).
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