Synthesis of 3-cyano-2-fluoropyridines

Article abstract of DOI:10.1016/j.jfluchem.2008.10.005

The synthesis of 3-cyano-2-fluoropyridines from readily available precursors was achieved via nucleophilic substitution of a leaving group in the 2-postion with KF or Bu₄NF in polar aprotic solvents such as DMF and DMSO. Ionic tetrahydrothiophe

Full text of DOI:10.1016/j.jfluchem.2008.10.005

Journal of Fluorine Chemistry 130 (2009) 236–240
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of 3-cyano-2-fluoropyridines
a
a
a
Anatoliy M. Shestopalov a, , Ludmila A. Rodinovskaya , Alexander E. Fedorov , Victor E. Kalugin ,
*
Kirill G. Nikishin a, Alexandr A. Shestopalov a, Andrei A. Gakh b,
*
a N.D. Zelinsky Institute of Organic Chemistry, 119991, Leninsky Pr. 47, Moscow, Russia
b Oak Ridge National Laboratory, Oak Ridge, TN 37831-6242, USA
A R T I C L E I N F O
A B S T R A C T
Article history:
The synthesis of 3-cyano-2-fluoropyridines from readily available precursors was achieved via
nucleophilic substitution of a leaving group in the 2-postion with KF or Bu4NF in polar aprotic solvents
such as DMF and DMSO. Ionic tetrahydrothiophenium fragment is the most effective leaving group, the
methanesulfonyl moiety is a somewhat less effective, and Br- and Cl- are the least effective. Relatively
mild conditions of the reaction between (2-pyridyl)-tetrahydrothiophenium salts and KF, as well as the
convenience of one-step synthesis of these salts from 2(1H)-pyridinethiones, make these salts the
compounds of choice for the preparation of ring-fluorinated pyridines.
Received 20 July 2008
Received in revised form 20 October 2008
Accepted 22 October 2008
Available online 31 October 2008
Keywords:
Fluoropyridines
Synthesis
ß 2008 Elsevier B.V. All rights reserved.
Nucleophilic substitution
1. Introduction
3-Cyano-2-fluoropyridines have been successfully used in
preparation of compounds with diverse spectrum of biological
2-Fluoropyridines are an important class of fluoroheterocyclic
compounds. They have found numerous applications in synthetic
organic chemistry as valuable building blocks [1–3], as well as in
medicinal chemistry as precursors of biologically active molecules,
radiotracers and radiopharmaceuticals [1,4–7]. Although many
different methods for the preparation of 2-fluoropyridines have
been published in the literature, regioselective synthesis remains a
challenging problem especially in the presence of other reactive
substituents. The classic method of synthesis of 2-fluoropyridines
entails diazotation of 2-aminopyridines in HF [8]. One of the best
methods for preparation of 2-fluoropyridines is based on reactions
of 2-halopyridines with KF, Bu4NF, and other sources of the
fluoride ion [9]. Direct fluorination of substituted pyridines [10]
and base-induced rearrangement of N-fluoropyridinium salts [11]
have been proposed for the preparation of 2-fluoropyridines.
Electrophilic fluorination has also been employed to prepare 2-
fluoropyridines; however, fluorination of pyridine with XeF2 or
XeF6 has shown to yield a mixture of 2- and 3-fluropyridines and
2,6-difluoropyridine [9]. 5-Aryl-3,4-dimethoxycabonyl-2-fluoro-
pyridines have been prepared by the reaction of difluromethyla-
ziridinium salts with dimethyl acetylenedicarboxylate [12].
activity. For example, these molecules have recently been
proposed as kinase inhibitors (A) [13], potassium channel
inhibitors (B) [14], and as acetylcholine receptor ligands (e.g., as
a central nervous system active agent, C) [15] (Fig. 1). Other 3-
cyano-2-fluoropyridine can potentially be used as promising
agents for the positron emission tomography (PET) [16]. Addi-
tionally, it has previously been demonstrated that 3-cyanopyr-
idines can be transformed into -amides, -carboxylic acids, and -
esters [17–19]. Furthermore, it has been shown on numerous
occasions that the 3-cyano group in pyridines easily participates in
intramolecular nucleophilic addition reactions leading to fused
heterocyclic systems [20–22].
2. Results and discussion
Polysubstituted 3-cyano-2-fluoropyridines are relatively diffi-
cult to prepare compounds due to the lack of convenient synthetic
methods [9]. One of the goals of the current effort is to develop
synthetic approaches for the preparation of these compounds from
readily available starting materials. The general synthetic scheme
includes nucleophilic substitution reactions of nucleofuge-con-
taining pyridines employing commonly used sources of nucleo-
philic fluoride ion, KF and Bu4NF (Scheme 1).
First, we investigated 2-chloro-3-cyanopyridines as precursors
for the desired fluoropyridines. We found that 3-cyano-2-
fluoropyridines 2a–c can be prepared from corresponding 2-
chloro-3-cyanopyridines 1a–c in 52–86% yield upon heating with
* Corresponding authors. Tel.: +1 865 574 1000; fax: +1 865 574 1260.
E-mail addresses: shchem@dol.ru (A.M. Shestopalov), gakhaa@ornl.gov
(A.A. Gakh).
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.10.005

A.M. Shestopalov et al. / Journal of Fluorine Chemistry 130 (2009) 236–240
237
Fig. 1. Biologically active 3-cyano-2-fluoropyridines.
reactions improved the yield by 11–28% (2-fluoropyridines 2b,d;
Method C, Scheme 3).
We also investigated the utility of readily available 3-
cyanopyridine-2(1H)-thiones [25–27] as starting materials for
the synthesis of Biologically active 3-cyano-2-fluoropyridines.
These compounds were first converted into 3-cyano-2-methane-
sulphonylpyridines 4 by a previously published protocol [28]. The
methanesulfonyl group in 4 was then successfully replaced with
fluorine using excess KF in DMF at 120–125 8C. This method gives
3-cyano-2-fluoropyridines 2b,f in good yields (72 and 75%, Method
D, Scheme 4).
In addition, we examined a possibility of conversion of 3-
cyanopyridine-2(1H)-thiones into 3-cyano-2-fluoropyridines via
intermediate tetrahydrothiophenium salts 6 (Method E, Scheme
5). Tetrahydrothiophene has previously been shown as an
excellent leaving group in the intramolecular addition-elimination
reaction [29], and we have envisioned that it will act as a good
nucleofuge in nucleophilic fluorination reactions. The tetrahy-
drothiophenium salts 6a,b were prepared according to the known
procedure [30] from corresponding pyridinethiones 5a,b, 1,4-
dibrombutane and KPF6 in 53–67% yields. Reaction of 6 with excess
KF in DMF in relatively mild conditions (70–75 8C) gave
Scheme 1.
excess of KF in DMSO at 120–140 8C (Method A, Scheme 2). The
limiting step of this approach is the synthesis of the starting
materials, 2-chloro-3-cyanopyridines, which can be prepared from
3-cyanopyridin-2(1H)-ones in moderate yields (40–62%) [9].
Substituted 2-bromopyridines can also be used for the
synthesis of corresponding 2-fluoropyridines. Contrary to 2-
chloro-3-cyanopyridines, 2-bromo-3-cyanopyridines can be easily
prepared in one step from acyclic reagents. For example, 2-bromo-
3-cyanopyridines 3a–c were prepared in up to 98% yields via
bromination of corresponding 2-aryl-3-aroyl-1,1-dicyanopro-
panes in acetic acid [23,24]. We found that heating of these 2-
bromo-3-cyanopyridines 3a–c with excess KF in DMF resulted in
formation of 2-fluoropyridines 2b,d,e in 62–76% yield (Method B,
Scheme 3). The use of more organic-soluble Bu4NF in these
corresponding 3-cyano-2-fluoropyridines
(Method E, Scheme 5).
2 in 65–70% yields
The structures of all reported compounds were elucidated by
means of infrared (IR) and multi-NMR (1H, 13C and 19F) spectro-
scopy, mass spectrometry (MS), and confirmed by elemental
analysis. The presence of CꢀN in fluoropyridines 2 was confirmed
by the characteristic absorption band at 2228–2236 cmÀ1 in IR
spectra. This band is shifted ꢁ10 cmÀ1 compared to the
corresponding 2-bromo-3-cyanopyridines (2218–2226 cmÀ1
)
[24,31]. This difference can be attributed to the presence of a
Scheme 2.
Scheme 3.

238
A.M. Shestopalov et al. / Journal of Fluorine Chemistry 130 (2009) 236–240
3. Conclusions
We have developed a practical synthetic approach towards 3-
cyano-2-fluoropyrines based on nucleophilic substitution of various
leaving groups at the 2-postion of the pyridine ring using KF or
Bu4NF in DMF and DMSO at elevated temperatures. The developed
protocols offer a simple and efficient way to make 3-cyano-2-
fluoropyridines from available 2-substituted-3-cyanopyridines. The
3-cyano group in these 2-fluoropyridines can potentially be further
modified, providing an efficient route to various fluoroheterocyclic
systems [17–19]. We continue to explore the use of 2-substituted-3-
cyanopyridines in the synthesis of 3-cyano-2-fluoropyridines and
their subsequent synthetic transformations.
Scheme 4.
strong electronegative fluorine atom next to the cyano group. The
same effect is observed in NMR 13C spectra where the signal of C2 is
shifted downfield (
further downfield (
not have aryl
-donors. The signal of fluorine atom in 19F NMR of 2-
fluoropyridines 2 is in the range of À52.2 to À66.4 ppm.
d
d
157.4–158.4) for compounds 2b,d–g, and even
162.3–164.2) for compounds 2a,c, which do
4. Experimental
1H NMR spectra were recorded on a Bruker AM-300 spectro-
meter (300.13 MHz). 13C NMR spectra were recorded on a Bruker
AC-200 spectrometer (50.32 MHz). 19F NMR spectra were recorded
on a Bruker AC-200 spectrometer (188.31 MHz). Chemical shifts of
1H were measured (ppm) relative to Me4Si as the internal standard,
13C – relative to DMSO-d6, and 19F – relative to CFCl3. IR-spectra
were recorded on a PerkinElmer 467 spectrophotometer in KBr
p
Based on the observed yields and reaction conditions (time and
temperature), it appears that the substitution reaction is the most
difficult in the case of 2-halopyridines and is much easier in the
case of tetrahydrothiophenium salts, with methanesulphonyl
derivatives being somewhere in between (Table 1). Observations
of the relative reactivity of these four leaving groups towards the
fluoride anion are in general agreement with the existing body of
theoretical and experimental data related to nucleophilic sub-
stitution reactions at the 2-position of the pyridine ring [9]. A
specific high reactivity of sulfonium salts compared to covalent
compounds can be attributed to Columb interactions between the
fluoride anion and cationic substrates [32]. This assumption is
further supported by the fact that the only known-to-date
enzymatic fluorination reaction also entails reaction of the fluoride
anion and a sulfonium salt [33].
pellets. MS spectra were recorded on
a Varian MAT-CH-6
instrument (EI, 70 eV). Thin-layer chromatography (TLC) was
performed on Silufol UV-254 silica gel (hexane–acetone 5:3).
‘‘Spray-dried’’ KF (Aldrich) and 1 M solution of Bu4NF in THF (5%
H2O, Acros) were used in all reactions.
4.1. 3-Cyano-2-fluoropyridines 2a–c. Method A
A mixture of 0.05 mol of 3-cyano-2-chloropyridine 1a–c and
8.7 g (0.15 mol) of KF in 30 ml of anhydrous DMSO was heated at
Scheme 5.
Table 1
Fluorination reaction yields and conditions for the methods A (–Cl, KF), B (–Br, KF), C (–Br, Bu4NF), D (–SO2Me, KF) and E (–S+(CH2)4, KF).
2-Fluoropyridine
R1
R2
H
R3
Starting material
Yield (%)
75
FÀ source
KF
Leaving group
Cl
Method
A
Reaction conditions
2a
2b
CH3
C6H5
CH3
C6H5
1a
DMSO, 140 8C, 8 h
H
1b
3a
3a
4a
86
62
90
72
KF
Cl
A
B
C
D
DMSO, 140 8C, 8 h
DMF, 135 8C, 14 h
DMF, 110 8C, 10 h
DMF, 125 8C, 4 h
KF
Br
Bu4NF
KF
Br
SO2Me
2c
H
H
(CH2)4
C6H5
1c
52
KF
Cl
A
DMSO, 140oC, 8 h
2d
4–CH3–C6H4
3b
3b
76
87
KF
Br
Br
B
C
DMF, 135 8C, 14 h
DMF, 110 8C, 10 h
Bu4NF
2e
2f
4–Cl–C6H4
H
H
C6H5
C6H5
3c
68
KF
Br
B
DMF, 135 8C, 14 h
4–OCH3–C6H4
4b
6a
75
65
KF
KF
SO2Me
S+(CH2)4
D
E
DMF, 125 8C, 4 h
DMF, 75 8C, 4 h
2g
C6H5
H
4–F–C6H4
6b
70
KF
S+(CH2)4
E
DMF, 75 8C, 4 h

A.M. Shestopalov et al. / Journal of Fluorine Chemistry 130 (2009) 236–240
239
120–140 8C with stirring for 7–8 h. The reaction mixture was
cooled to room temperature, poured into crushed ice (200 g), and
extracted with CHCl3 (3 Â 50 ml). The organic extract was washed
with water, dried over Na2SO4, and filtered through a short layer of
silica gel. The organic solvent was evaporated; the residue was
taken up in boiling n-hexane (50 ml), filtered through a paper filter,
and placed in a refrigerator (5 8C) overnight. The precipitate was
collected by filtration and dried.
(DMSO-d6):
d 113.31, 118.45, 127.70, 129.16, 131.49, 135.71,
158.42. 19F NMR (DMSO-d6):
d
À61.17; m/z: 308 [M]+ (100). Found
(%): C, 70.10; H, 3.29; N, 8.94. C18H10ClFN2 calculated (%): C, 70.02;
H, 3.26; N, 9.07.
4.9. 3-Cyano-2-fluoropyridines 2b,d. Method C
A mixture of 0.01 mol of 3-cyano-2-bromopyridine 3a,b, 15 ml
(0.015 mol) of a 1 M solution of Bu4NF in THF, and 15 ml of
anhydrous DMF was heated at 105–110 8C with stirring for 10 h.
The reaction mixture was cooled to room temperature and poured
into crushed ice (200 g). The precipitate was filtered and
recrystallized from CHCl3/MeOH (1:2).
4.2. 3-Cyano-4,6-dimethyl-2-fluoropyridine (2a)
Yield 5.62 g (75%), m.p. 85 8C (hexane). IR,
1H NMR (DMSO-d6):
NMR (DMSO-d6):
n
, cmÀ1: 2232 (CꢀN).
d
2.47 (s, 3H); 2.52 (s, 3H); 7.36 (s, 1H). 13C
d
19.63 (CH3), 23.74 (CH3), 112.65, 122.85,
149.57, 157.05, 161.75, 164.24. 19F NMR (DMSO-d6):
d
À63.93; m/
4.10. 3-Cyano-4,6-diphenyl-2-fluoropyridine (2b)
Yield 2.47 g (90%).
z: 150 [M]+ (100). Found (%): C, 64.02; H, 4.76; N, 18.57. C8H7FN2
calculated (%): C, 63.99; H, 4.70; N, 18.66.
4.3. 3-Cyano-4,6-diphenyl-2-fluoropyridine (2b)
4.11. 3-Cyano-2-fluoro-4-(4-methylphenyl)-6-phenypyridine (2d)
Yield 2.51 g (87%).
Yield 11.78 g (86%), m.p. 143 8C. IR,
n
, cmÀ1: 2228 (CꢀN). 1H
NMR (DMSO-d6):
NMR (DMSO-d6):
d
7.62 (m, 5H); 7.64 (m, 5H); 8.35 (s, 1H). 13C
d
118.35, 127.58, 128.67, 128.73, 128.97, 129.09,
4.12. 3-Cyano-2-fluoropyridines 2b,f. Method D
129.21, 130.52, 130.73, 131.40, 131.47, 134.68, 135.23, 157.92. 19
F
NMR (DMSO-d6):
d
À52.29; m/z: 274 [M]+ (100). Found (%): C,
A mixture of 0.01 mol of 3-cyano-2-methanesulphonylpyridine
4a,b and 1.16 g (0.02 mol) of KF in 20 ml of anhydrous DMF was
heated at 120–125 8C with stirring for 4 h. The reaction mixture
was cooled to room temperature and poured into crushed ice
(200 g), and the precipitate was filtered and recrystallized from
CHCl3/MeOH (1:2).
78.79; H, 4.05; N, 10.23. C18H11FN2 calculated (%): C, 78.82; H, 4.04;
N, 10.21.
4.4. 3-Cyano-2-fluoro-5,6-tetramethylenepyridine (2c)
Yield 4.58 g (52%), m.p. 45 8C (hexane). IR,
1H NMR (DMSO-d6):
2H); 7.72 (s, 1H). 13C NMR (DMSO-d6):
n
, cmÀ1: 2236 (CꢀN).
d
1.78–1.96 (m, 4H); 2.79 (m, 2H); 2.94 (m,
20.18, 27.53, 32,43,
112.98, 130.64, 144.16, 157.47, 161.91, 162.32. 19F NMR (DMSO-
4.13. 3-Cyano-4,6-diphenyl-2-fluoropyridine (2b)
Yield 1.97 g (72%).
d
d6):
d
À66.41; m/z: 176 [M]+ (100). Found (%): C, 68.13; H, 5.17; N,
15.92. C10H9FN2 calculated (%): C, 68.17; H, 5.15; N, 15.90.
4.14. 3-Cyano-2-fluoro-4-(4-methoxylphenyl)-6-phenypyridine (2f)
4.5. 3-Cyano-2-fluoropyridines 2b,d,e. Method B
Yield 2.28 g (75%), m.p. 193 8C (CHCl3/MeOH). IR,
n
, cmÀ1: 2228
d 3.88 (s, 3H); 7.19 (d, 2H, J = 8.3 Hz);
(CꢀN). 1H NMR (DMSO-d6):
A mixture of 0.01 mol of 3-cyano-2-bromopyridine 3a–c and
1.7 g (0.03 mol) of KF in 15 ml of anhydrous DMF was heated at
130–135 8C with stirring for 14 h. The reaction mixture was cooled
to room temperature and poured into crushed ice (200 g). The
precipitate was filtered and recrystallized from CHCl3/MeOH (1:2).
7.56–8.25 (m, 5H); 7.84 (d, 2H, J = 8.3 Hz); 8.18 (s, 1H). 13C NMR
(DMSO-d6):
130.52, 131.31, 135.47, 157.42. 19F NMR (DMSO-d6):
m/z: 304 [M]+ (100). Found (%): C, 75.03; H, 4.30; N, 9.24.
19H13FN2O calculated (%): C, 74.99; H, 4.31; N, 9.21.
d
55.52, 114.51, 118.09, 126.93, 127.63, 129.12,
d
À61.40;
C
4.6. 3-Cyano-4,6-diphenyl-2-fluoropyridine (2b)
Yield 1.70 g (62%).
4.15. Tetrahydrothiophenium salts 6a,b
A solution of 0.03 M of 2(1H)-pyridinethione 5a,b in 15 ml of
anhydrous DMF; 6.2 g (0.045 mol) K2CO3; and 13 g (0.06 mol) of
1,4-dibrombutane was heated at 45–50 8C for 3 h. After that,
excess 1,4-dibrombutane and most of the solvent were removed
under reduced pressure. The residue was treated with 200 ml of
acetone and 9.2 g (0.05 mol) of KPF6. The resulting mixture was
stirred at 20 8C for 2 h. Most of the solvent was evaporated, and the
residue was treated with 100 ml of Et2O. The mixture was
refrigerated overnight, and the precipitate was collected by
filtration and washed with water (3 Â 20 ml), EtOH (2 Â 20 ml),
and Et2O (3 Â 20 ml).
4.7. 3-Cyano-2-fluoro-4-(4-methylphenyl)-6-phenypyridine (2d)
Yield 2.19 g (76%), m.p. 214–215 8C (CHCl3/MeOH). IR,
n
, cmÀ1
d 2.42 (s, 3H); 7.42 (d, 2H,
:
2228 (CꢀN). 1H NMR (DMSO-d6):
J = 8.7 Hz); 7.57 (m, 3H); 7.73 (d, 2H, J = 8.7 Hz); 8.12 (s, 1H); 8.18
(m, 2H). 13C NMR (DMSO-d6):
d 21.50 (CH3), 118.84, 128.82,
129.32, 129.73, 129.93, 130.22, 133.73, 135, 137.52, 140.01,
158.07. 19F NMR (DMSO-d6):
Found (%): C, 79.04; H, 4.60; N, 9.77. C19H13FN2 calculated (%): C,
79.15; H, 4.54; N, 9.72.
d
À61.30; m/z: 288 [M]+ (100).
4.16. [3-Cyano-4-(4-methoxyphenyl)-6-phenylpyrid-2-yl]-
4.8. 3-Cyano-2-fluoro-4-(4-chlorophenyl)-6-phenypyridine (2e)
tetrahydrothiophenium hexafluorophosphate (6a)
Yield 2.09 g (68%), m.p. 198–199 8C (CHCl3/MeOH). IR,
n
, cmÀ1
7.54–7.56 (m, 3H); 7.70 (d, 2H,
:
Yield 8.4 g (54%), m.p. 197–199 8C (acetone/Et2O). 1H NMR
2236 (CꢀN). 1H NMR (DMSO-d6):
d
(DMSO-d6):
d 2.23 (m, 4H), 3.77 (m, 2H), 3.89 (m, 2H), 3.94 (s, 3H),
J = 8.5 Hz); 7.85 (d, 2H, J = 8.5 Hz); 8.22–8.24 (m, 3H). 13C NMR
7.24 (d, 2H, J = 8.4 Hz), 7.78 (d, 2H, J = 8.4 Hz), 7.54–8.26 (m, 5H),

240
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4.17. [3-Cyano-4-(4-fluorophenyl)-6-phenylpyrid-2-yl]-
tetrahydrothiophenium hexafluorophosphate (6b)
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(DMSO-d6):
7.74–8.36 (m, 7H), 8.28 (s, 1H). Found (%): C, 52.47; H, 3.72; N, 5.32.
22H18F7N2SP calculated (%): C, 52.18; H, 3.58; N, 5.53.
d 2.26 (m, 4H), 3.82 (m, 2H), 3.94 (m, 2H), 7.38 (m, 2H),
C
4.18. 3-Cyano-2-fluoropyridines 2f,g. Method E
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5508.
A mixture of 0.01 mol of tetrahydrothiophenium salt 6a,b and
0.87 g (0.015 mol) of KF in 20 ml of anhydrous DMF was heated at
70–75 8C with stirring for 4 h, following which the reaction
mixture was cooled to room temperature and poured into crushed
ice (200 g). The precipitate was filtered and recrystallized from
CHCl3/MeOH (1:2).
4.19. 3-Cyano-2-fluoro-4-(4-methoxylphenyl)-6-phenypyridine (2f)
Yield 1.98 g (65%).
4.20. 3-Cyano-2-fluoro-6-(4-fluorophenyl)-4-phenypyridine (2g)
[19] X. Zheng, K.J. Hodgetts, H. Brielmann, A. Hutchison, F. Burkamp, J.A. Brian, P.
Blurton, R. Clarkson, J. Chandrasekhar, R. Bakthavatchalam, S. De Lombaert, M.
Crandalla, D. Cortrighta, C.A. Blum, Bioorg. Med. Chem. Lett. 16 (2006) 5217–
5221.
[20] L.A. Rodinovskaya, A.M. Shestopalov, A.V. Gromova, A.A. Shestopalov, J. Comb.
Chem. 10 (2008) 313–322.
[21] L.A. Rodinovskaya, A.M. Shestopalov, A.V. Gromova, A.A. Shestopalov, Synthesis
14 (2006) 2357–2370.
[22] L.A. Rodinovskaya, E.V. Belukhina, A.M. Shestopalov, V.P. Litvinov, Russ. Chem.
Bull. 43 (1994) 449–457.
Yield 2.04 g (70%), m.p. 211 8C (CHCl3/MeOH). IR,
n
, cmÀ1: 2228
d 7.27–7.41 (m, 2H); 7.57–7.69 (m,
(CꢀN). 1H NMR (DMSO-d6):
3H); 7.79–7.92 (m, 2H); 8.14–8.34 (m, 2H), 8.23 (s, 1H). 13C NMR
(DMSO-d6):
d 113.8, 114.9, 116.8, 118.2, 119.4, 129.2, 130.07,
131.02, 132.05, 135.12, 157.85. 19F NMR (DMSO-d6):
d
À58.41,
À105.13; m/z: 292 [M]+ (100). Found (%): C, 74.00; H, 3.47; N, 9.65.
[23] A.M. Shestopalov, V.K. Promonenkov, Y.A. Sharanin, L.A. Rodinovskaya, S.Y.
Sharanin, Zh. Org. Chim. (Russ.) 20 (1984) 1517–1538.
[24] Y.A. Sharanin, V.K. Promonenkov, A.M. Shestopalov, Zh. Org. Chim. (Russ.) 18
(1982) 630–640.
C
18H10F2N2 calculated (%): C, 73.97; H, 3.45; N, 9.58.
Acknowledgments
[25] V.P. Litvinov, L.A. Rodinovskaya, Yu.A. Sharanin, A.M. Shestopalov, A. Senning,
Sulfur Rep. 13 (1992) 1–155.
[26] A.M. Shestopalov, V.P. Kislyi, E.Y. Kruglova, K.G. Nikishin, V.V. Semenov, A.C.
Buchanan, A.A. Gakh, J. Comb. Chem. 2 (2000) 24–28.
[27] V.P. Kislyi, K.G. Nikishin, E.Y. Kruglova, A.M. Shestopalov, V.V. Semenov, A.A. Gakh,
A.C. Buchanan, Tetrahedron 52 (1996) 10841–10848.
[28] V.E. Kalugin, A.M. Shestopalov, V.P. Litvinov, Russ. Chem. Bull. 55 (2006) 529–534.
[29] A.A. Shestopalov, L.A. Rodinovskaya, A.M. Shestopalov, S.G. Zlotin, V.N. Nesterov,
Synlett 15 (2003) 2309–2312.
This research was sponsored by the IPP program. Oak Ridge
National Laboratory is managed and operated by UT-Battelle, LLC,
under contract DE-AC05-00OR22725. The research at the Zelinsky
Institute of Organic Chemistry was performed for the U.S.
Department of Energy under contract DE-AC01-00N40184 with
Kurchatov Institute. This paper is
Discovery Chemistry Project.
a contribution from the
[30] J. Srogl, G.D. Allred, L.S. Liebeskind, J. Am. Chem. Soc. 119 (1997) 12376–
12377.
[31] A.M. Shestopalov, Yu.M. Emel’yanova, in: V.G. Kartsev (Ed.), Selected Methods for
Synthesis and Modification of Heterocyclices, vol. 2, IBS Press, Moscow, 2003, pp.
363–390.
References
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