Synthesis, Properties, and Reactivity of N,N'-Difluorobipyridinium and Related Salts and Their Applications as Reactive and Easy-To-Handle Electrophilic Fluorinating Agents with High Effective Fluorine Content

Article abstract of DOI:10.1021/jo972338q

N,N′-Difluoro-2,2′-, -2,4′-, -3,3′-, -4,4′-bipyridinium and substituted N,N′-difluoro-2,2′-bipyridinmm bis(triflates), bis(tetrafluoroborates), bis(hexafluorophosphates), and bis(hexafluoroantimonates) 1-9 were synthesized in high yields by the direct fluorination of a mixture of a bipyridyl and a Lewis acid, a Br?nsted acid, or the alkali metal salt of an acid. The higher homologues, trimer 10 and polymer 11, were also synthesized. Unsubstituted or electron-donating group-substituted N,N′- difluorobipyridinium salts are stable nonhygroscopic crystals, while the electron-withdrawing group- substituted N,N′-diflurobipyridinium salts 3, 5, and 6 are moisture-sensitive crystals. Hydrolysis of 1b in boiling water gave 3,3′-dihydroxy-2,2′-bipyridyl. The reactivity determination indicated that the fluorinating capability decreased in the order 2,2′- ? 2,4' > 3,3′- ≈ 4,4′-isomer ? N-fluoropyridinium salt and that the two N-F moieties in a molecule were effective for fluorination. This fluorination occurred in a step-by-step manner, and the reactivity difference between the first and second fluorinations was very small. N,N′-Difluoro-2,2′-bipyridinium bis(tetrafluoroborate) (1b) is thus shown to be a highly reactive and easy-to-handle electrophilic fluorinating agent with the high effective fluorine content (103.3 g/kg) for preparing many fluoro organic compounds.

Full text of DOI:10.1021/jo972338q

J . Org. Chem. 1998, 63, 3379-3385
3379
Syn th esis, P r op er ties, a n d Rea ctivity of N,N′-Diflu or obip yr id in iu m
a n d Rela ted Sa lts a n d Th eir Ap p lica tion s a s Rea ctive a n d
Ea sy-To-Ha n d le Electr op h ilic F lu or in a tin g Agen ts w ith High
Effective F lu or in e Con ten t1
Teruo Umemoto,* Masayuki Nagayoshi, Kenji Adachi, and Ginjiro Tomizawa
MEC Laboratory, Daikin Industries, Ltd., Miyukigaoka 3, Tsukuba, Ibaraki 305-0841, J apan
Received December 31, 1997
N,N′-Difluoro-2,2′-, -2,4′-, -3,3′-, -4,4′-bipyridinium and substituted N,N′-difluoro-2,2′-bipyridinium
bis(triflates), bis(tetrafluoroborates), bis(hexafluorophosphates), and bis(hexafluoroantimonates)
1-9 were synthesized in high yields by the direct fluorination of a mixture of a bipyridyl and a
Lewis acid, a Brønsted acid, or the alkali metal salt of an acid. The higher homologues, trimer 10
and polymer 11, were also synthesized. Unsubstituted or electron-donating group-substituted N,N′-
difluorobipyridinium salts are stable nonhygroscopic crystals, while the electron-withdrawing group-
substituted N,N′-diflurobipyridinium salts 3, 5, and 6 are moisture-sensitive crystals. Hydrolysis
of 1b in boiling water gave 3,3′-dihydroxy-2,2′-bipyridyl. The reactivity determination indicated
that the fluorinating capability decreased in the order 2,2′- . 2,4′ > 3,3′- ≈ 4,4′-isomer .
N-fluoropyridinium salt and that the two N-F moieties in a molecule were effective for fluorination.
This fluorination occurred in a step-by-step manner, and the reactivity difference between the first
and second fluorinations was very small. N,N′-Difluoro-2,2′-bipyridinium bis(tetrafluoroborate)
(1b) is thus shown to be a highly reactive and easy-to-handle electrophilic fluorinating agent with
the high effective fluorine content (103.3 g/kg) for preparing many fluoro organic compounds.
In tr od u ction
fluorinating agents.2,3 These compounds include N-
fluorosulfonamides,4 N-fluoropyridinium salts,5 N-fluo-
ropyridinium-2-sulfonates,6 N-fluorobis(trifluoromethane-
sulfonyl)imides,7 N-fluorosultums,8 N-fluorodisulfoni-
mides,9 N-alkyl-N′-fluoro-1,4-diazoniabicyclo[2.2.2]octane
salts,10 N-fluoro-N′-hydroxy-1,4-diazoniabicyclo[2.2.2]-
octane salts,11 N,N′-difluoro-1,4-diazoniabicyclo[2.2.2]-
octane salts,12 and N-fluoro oxathiazine dioxides.13 Some
of these reagents appear on the market.14 But due to
the low effective fluorine content (54-78 g/kg15), reactive
reagents possessing more effective fluorine content are
desired. The authors have recently produced highly
Electrophilic fluorinating agents are required for pre-
paring fluoro organic compounds in advanced organic
synthesis at present,2 and many compounds with an N-F
moiety have thus been made available as electrophilic
* To whom correspondence should be addressed. Phone: +81 298
58 5070. Fax: +81 298 58 5082. E-mail: umemoto@mec.daikin.co.jp.
(1) Presented at the 20th National Meeting on Fluorine Chemistry
of J apan, Nagoya, October 30, 1996, Abstract, No. P-27; J apanese
Patent Application 94-282491 (October 22, 1994).
(2) (a) Umemoto, T. Rev. Heteroatom. Chem. 1994, 10, 123. (b) New
Fluorinating Agents in Organic Syntheses; German, L., Zemskov, S.,
Eds.; Springer-Verlag: New York, 1989. (c) Purrington, S. T.; Kagen,
B. S.; Patrick, T. B. Chem. Rev. 1986, 86, 997. (d) Rozen, S.; Filler, R.
Tetrahedron 1985, 41, 1111. (e) Wilkinson, J . A. Chem. Rev. 1992, 92,
505.
(3) Lal, G. S.; Pez, G. P.; Syvret, R. G. Chem. Rev. 1996, 96, 1737.
(4) (a) Barnette, W. E. J . Am. Chem. Soc. 1984, 106, 452. (b)
Differding, E.; Lang, R. W. Helv. Chim. Acta 1989, 72, 1248. (c) Banks,
R. E.; Khazaei, A. J . Fluorine Chem. 1990, 46, 297. (d) Differding, E.;
Ruegg, G. M.; Lang, R. W. Tetahedron Lett. 1991, 32, 1779.
(5) (a) Umemoto, T.; Tomita, K. Tetrahedron Lett. 1986, 27, 3271.
(b) Umemoto, T.; Kawada, K.; Tomita, K. Tetrahedron Lett. 1986, 27,
4465. (c) Umemoto, T.; Tomizawa, G. Bull. Chem. Soc. J pn. 1986, 59,
3625. (d) Umemoto, T.; Fukami, S.; Tomizawa, G.; Harasawa, K.;
Kawada, K.; Tomita, K. J . Am. Chem. Soc. 1990, 112, 8563. (e)
Umemoto, T.; Tomita, K.; Kawada, K. Org. Synth. 1990, 69, 129. (f)
Umemoto, T.; Harasawa, K.; Tomizawa, G.; Kawada, K.; Tomita, K.
Bull. Chem. Soc. J pn. 1991, 64, 1081. (g) Umemoto, T.; Harasawa, K.;
Tomizawa, G.; Kawada, K.; Tomita, K. J . Fluorine Chem. 1991, 53,
369. (h) Shimizu, I.; Ishii, H. Tetrahedron 1994, 487. (i) Page, P. C.
B.; Hussain, F.; Maggs, J . L.; Morgan, P.; Park, B. K. Tetrahedron 1990,
46, 2059. (j) Hebel, D.; Kirk, K. L. J . Fluorine Chem. 1990, 47, 179.
(k) Poss, A. J .; Van der Puy, M.; Nalewajek, D.; Shia, G. A.; Wagner,
W. J .; Frenette, R. L. J . Org. Chem. 1991, 56, 5962. (l) Dauben, W. G.;
Greenfield, L. J . J . Org. Chem. 1992, 57, 1597. (m) Naruta, Y.; Tani,
F.; Maruyama, K. Tetrahedron Lett. 1992, 33, 1069. (n) Ihara, M.;
Taniguchi, N.; Kai, T.; Fukumoto, K. J . Chem. Soc., Perkin Trans. 1
1992, 221. (o) Sato, M.; Kitazawa, N.; Kaneko, C. Heterocycles 1992,
33, 105. (p) Strekowski, L.; Kiselyov, A. S. Adv. Heterocyc. Chem. 1995,
62, 1. (q) Ueno, T.; Toda, H.; Yasunami, M.; Yoshifuji, M. Chem. Lett.
1995, 169. (r) Tius, M. A.; Kawakami, J . K.; Hill, W. A. G.; Makriy-
annis, A. J . Chem. Soc., Chem. Commun. 1996, 2085.
reactive
and
easy-to-handle
N,N′-difluoro-1,4-
diazoniabicyclo[2.2.2]octane salts each containing two
N-F moieties in a molecule.12 One N-F moiety is
effective for fluorination, and the other promotes the
fluorination reactivity. Thus, its effective fluorine con-
tent is 59 g/kg at most. N-Fluoropyridinium tetrafluo-
roborate previously synthesized by the authors5b-d is not
particularly reactive but has a high effective fluorine
content (102.7 g/kg). The studies on N-fluoropyridinium
salts by the authors have also shown that the fluorination
(6) Umemoto, T.; Tomizawa, G. J . Org. Chem. 1995, 60, 6563.
(7) (a) Singh, S.; DesMarteau, D. D.; Zuberi, S. S.; Witz, M.; Huang,
H.-N. J . Am. Chem. Soc. 1987, 109, 7194. (b) Xu, Z.-Q.; DesMarteau,
D. D.; Gotoh, Y. J . Chem. Soc., Chem. Commun. 1991, 179. (c)
Pennington, W. T.; Resnati, G.; DesMarteau, D. D. J . Org. Chem. 1992,
57, 1536. (d) Resnati, G.; DesMarteau, D. D. J . Org. Chem. 1991, 56,
4925. (e) DesMarteau, D. D.; Xu, Z.-Q.; Witz, M. J . Org. Chem. 1992,
57, 629. (f) Xu, Z.-Q.; Desmarteau, D. D.; Gotoh, Y. J . Fluorine Chem.
1992, 58, 71. (g) Resnati, G.; DesMarteau, D. D. J . Org. Chem. 1992,
57, 4281. (h) Xu, Z.-Q.; DesMarteau, D. D. J . Chem. Soc., Perkin Trans.
1 1992, 313.
(8) Differding, E.; Lang, R. W. Tetrahedron Lett. 1988, 29, 6087.
(9) (a) Davis, F. A.; Han, W. Tetrahedron Lett. 1991, 32, 1631. (b)
Differding, E.; Ofner, H. Synlett 1991, 187. (c) Differding, E.; Duthaler,
R. O.; Krieger, A.; Ruegg, G. M.; Schmit, C. Synlett 1991 395. (d) Davis,
F. A.; Han, W.; Murphy, C. K. J . Org. Chem. 1995, 60, 4730.
S0022-3263(97)02338-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/15/1998

3380 J . Org. Chem., Vol. 63, No. 10, 1998
Umemoto et al.
Sch em e 1
F igu r e 1.
salt of an acid in acetonitrile or in a mixture of acetoni-
trile and formic acid at -40 to 0 °C with 10-20% F2/90-
80% N2. The reaction conditions and results are specified
in Table 1. Fluorination yields were affected by the
solubility of the complexes and salts of the bipyridyls with
the Lewis and Brønsted acids. To enhance fluorination
yields of poorly soluble complexes and salts, a 49:1 or 50:1
(v/v) mixture of acetonitrile and formic acid or excess
acetonitrile as the solvent, fluorine in large excess, and
slightly less acid (1.84-1.97 molar equiv) were used.
Conjugated N,N′-difluoro-2,2′-, -2,4′- and -4,4′-bipyri-
dinium bis(triflates), 1a , 7a , and 9a , were synthesized
in high yields by the fluorination of a 1:2 molar mixture
of bipyridyl and triflic acid (runs 1, 2 and 4); this mixture
is a dihydrogen salt of the bipyridyl with triflic acid. It
was not possible by this method to produce a nonconju-
gated 3,3′-isomer 8a , and the starting dihydrogen salt of
3,3′-bipyridyl with triflic acid remained unreacted. This
outstanding difference between conjugated and noncon-
jugated isomers cannot be explained at present, but
possibly it may be due to interactions of π-electrons of
one ring of the dihydrogen bipyridinium salts with F2,
which may activate the NH site of the other ring in the
conjugated system. Triflate 8a was thus synthesized by
the fluorination of free 3,3′-bipyridyl in the presence of
lithium triflate (run 3).
reactivity varies with the electron density of the N-F
site, and electron-withdrawing group-substitution of N-
fluoropyridiniums enhances the reactivity.5b-d,6 Its dimer-
ic N,N′-difluorobipyridinium salt was thus made into a
desired fluorinating agent, because each of two N-
fluoropyridinium moieties could act not only as a fluorine
source but also as an electron-withdrawing substituent.
Recently, Banks et al. reported the synthesis of N,N′-
difluoro-4,4′-bipyridinium bis(triflate), N-fluoro-N′-meth-
yl-4,4′-bipyridinium bis(triflate), and N-fluoro-4-(4′-
pyridyl)pyridinium tetrafluoroborate-BF3 complex.16 This
paper presents the synthesis, properties, and reactivity
of a series of N,N′-difluorobipyridinium and related salts,
and the 2,2′-isomeric salt is assessed for its usefulness
as an electrophilic fluorinating agent.
Resu lts a n d Discu ssion
Syn th esis of N,N′-Diflu or obip yr id in iu m a n d Re-
la ted Sa lts. Isomeric N,N′-difluorobipyridinium salts
and derivatives 1-9 (Scheme 1) and higher homologues
10 and 11 (Figure 1) were synthesized by the direct
fluorination of a mixture of a bipyridyl or its homologue
and a Lewis acid, a Brønsted acid, or the alkali metal
2,2′-Bis(tetrafluoroborate) 1b was synthesized by the
fluorination of a 1:2 molar mixture of bipyridyl and BF3
in acetonitrile at -20 °C and more efficiently in a 50:1
(v/v) mixture of acetonitrile and formic acid at 0 °C. The
latter method is particularly advantageous, since the
final product 1b is obtained as pure crystals from the
starting homogeneous reaction solution with the course
of fluorination and pure 1b is easily produced in high
yield by filtering the reaction mixture after fluorination.
This method was successfully conducted on a large scale
using 4 mol of 2,2′-bipyridyl.17
N,N′-Difluoro-2,4′-bipyridinium bis(tetrafluoroborate)
(7b) and N,N′-difluoro-4,4′-bipyridinium bis(tetrafluo-
roborate) (9b) were obtained by the fluorination of a
1:1.95-1.96 molar mixture of bipyridyl and BF3 (runs 8
and 9), since the 1:2 complex of 2,4′-bipyridyl or 4,4′-
(10) (a) Banks, R. E.; Mohialdin-Khaffaf, S. N.; Lal, G. S.; Sharif,
I.; Syvret, R. G. J . Chem. Soc., Chem. Commun. 1992, 595. (b) Lal, G.
S. J . Org. Chem. 1993, 58, 2791. (c) Banks, R. E.; Lawrence, N. J .;
Popplewell, A. L. J . Chem. Soc., Chem. Commun. 1994, 343. (d)
Hodson, H. F.; Madge, D. J .; Slawin, A. N. Z.; Widdowson, D. A.;
Williams, D. J . Tetrahedron 1994, 50, 1899. (e) Stavber, S.; Sotler, T.;
Zupan, M. Tetrahedron Lett. 1994, 35, 1105. (f) Zupan, M.; Iskra, J .;
Stavber, S. J . Fluorine Chem. 1995, 70, 7. (g) Zupan, M.; Iskra, J .;
Stavber, S. J . Org. Chem. 1995, 60, 259. (h) Banks, R. E.; Lawrence,
N. J .; Popplewell, A. L. Synlett 1994, 831. (i) Abdul-Ghani, M.; Banks,
R. E.; Besheesh, M. K.; Sharif, I.; Syvret, R. G. J . Fluorine Chem. 1995,
73, 255. (j) Burkart, M. D.; Zhang, Z.; Hung, S.-C.; Wong, C.-H.; J .
Am. Chem. Soc. 1997, 119, 11743.
(11) (a) Stavber, S.; Zupan, M.; Poss, A. J .; Shia, G. A. Tetrahedron
Lett. 1995, 36, 6769. (b) Stavber, S.; Zupan, M. Synlett 1996, 693. (c)
Stavber, S.; Zupan, M. Chem. Lett. 1996, 1077. (d) Stavber, S.; Pecan,
T. S.; Papez, M.; Zupan, M. J . Chem. Soc., Chem. Commun. 1996, 2247.
(e) Stavber, S.; Zupan, M. Tetrahedron Lett. 1996, 37, 3591.
(12) (a) Umemoto, T.; Nagayoshi, M. Bull. Chem. Soc. J pn. 1996,
69, 2287. (b) Banks, R. E.; Besheesh, M. K. J . Fluorine Chem. 1995,
74, 165.
(13) Cabrera, I.; Appel, W. K. Tetrahedron 1995, 51, 10205.
(14) N-Fluoropyridinium salts (Onoda Fluorinates, FP-T and FP-B
Series), Chichibu Onoda Corp.; N-fluoropyridinium-2-sulfonates (MEC-
01 Series), Daikin Chemical Sales Co.; N-chloromethyl-N′-fluoro-1,4-
diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor, F-TEDA-
BF4), Air Products and Chemicals, Inc.; N-fluoropyridinium pyridine
heptafluorodiborate (Accufluor, NFPy), N-fluorobenzenesulfonimide
(Accufluor, NFSi), N-fluoro-N′-hydroxy-1,4-diazoniabicyclo[2.2.2]octane
bis(tetrafluoroborate) (Accufluor, NFTh), Allied Signal Inc.
(15) Effective fluorine contents: 54 g/kg for Selectfluor,14 59 g/kg
for NFTh,14 75 g/kg for Onoda Fluorinate FP-B800 (N-fluoro-2,6-
dichloropyridinium tetrafluoroborate).14.
(17) A large scale synthesis of N,N′-difluoro-2,2′-bipyridinium bis-
(tetrafluoroborate) (1b) was carried out as follows: 2,2′-bipyridyl (4
mol, 625 g), CH3CN (10.0 L), and formic acid (0.2 L) were placed in
the reactor of a fluorination apparatus.5c,e Commercially available CH3-
CN and formic acid as the solvents were used without further
purification or dryness. A separable flat-bottom type of cylindrical
stainless reactor (20 L, 30 cm L) was used, the inside of which is coated
with a fluoro resin. To the solution was added a BF3/CH3CN solution
(16.0 wt%, 3.9 L), and then the charged reactor was purged with N2
and placed on an ice bath at 0 °C. A 20% F2-80% N2 (v/v) gas mixture
was then introduced at a flow rate of 4.5 to 3.0 L min-1 just above the
surface of the rapidly stirred (950 rpm) reaction mixture. A cornical
nozzle was used so that the fluorination proceeded rapidly; the nozzle
made the F2/N2 gas contact the surface of the solution very effectively.
After the flow of F2 (8.6 mol) was stopped, only N2 was passed through
the flask at a rate of 80 mL min-1 for 30 min. The resulting precipitate
was collected by filtration under dry atmosphere and was washed with
CH3CN (1 L × 2) to give 1278 g (87%) of pure 1b. The crystals were
dried at 50 °C for 5 h under reduced pressure.
(16) Banks, R. E.; Besheesh, M. K.; Mohialdin-Khaffaf, S. N.; Sharif,
I. J . Fluorine Chem. 1997, 81, 157.

Synthesis of N,N′-Difluorobipyridinium and Related Salts
J . Org. Chem., Vol. 63, No. 10, 1998 3381
Ta ble 1. Syn th esis of N,N′-Diflu or obip yr id in iu m Sa lts a n d Rela ted Sa lts
bipyridyl/acid
or salt/F2
(molar ratio)
solvent
(mL)
acid or
salt
temp
(°C)a
run
bipyridyl
mmol
product
yield (%)b
1
2
3
4
5
6
7
8
9
2,2′-
2,4′-
3,3′-
4,4′-
2,2′-
2,2′-
2,2′-
2,4′-
4,4′-
2,4′-
4,4′-
5
5
5
5
5
25
6
10.3
4.26
2.1
9.18
6
1.09
3.2
0.88
3
CH3CN(20)
CH3CN(20)
CH3CN(10)
CH3CN(20)
CH3CN(20)
TfOH
TfOH
TfOLi
TfOH
BF3
BF3
HBF4
BF3
1/2/2.3
1/2/2.3
1/2/3
1/2/2.3
1/2/3
1/2/2.2
1/2/5.4
1/1.96/4.4
1/1.95/6.1
1/1.91/4.4
1/1.95/4.4
1/1.9/4.6
1/2.01/4.4
1/1.84/4.2
1/2.0/4.4
1/1.97/4.4
1/2.95/6.7
1/1/3.7
-20
-20
-40
-20
-20
0
-20
-20
0
-20
-20
-20
-20
-20
-20
-20
-20
-20
1a
7a
8a
9a
1b
1b
1b
7b
9b
7c
9d
2b
3b
4b
5d
6a
10
11
86
92
75
91
87
89
90
86
95
64
91
73
79
64
97
72
CH3CN/HCOOHd (76.5) 50/1 v/v
CH3CN(100)
CH3CN(40)
CH3CN/HCOOHd (8.57) 49/1 v/v
CH3CN(30)
BF3
10c
11
12
13
14
15
16
17
18
HPF6
SbF5
BF3
BF3
BF3
SbF5
TfOH
SbF5
SbF5
CH3CN(40)
CH3CN(24)
CH3CN(2.2)
CH3CN(12)
CH3CN(1.8)
CH3CN(15)
CH3CN(30)
CH3CN(50)
4,4′-diCH3-2,2′-
4,4′-diCl-2,2′-
4,4′-diC6H5-2,2′-
4,4′-diCO2CH3-2,2′-
5,5′-diCF3-2,2′
terpyridine
2.36
4.47
quante
quante
polypyridine
Bath temperature. Isolated yield. c In this experiment, a mixture of 2.0 mmol of N,N′-dihydro-2,4′-bipyridinium bis(hexafluorophos-
phate) and 0.1 mmol of 2,4′-bipyridyl was used as the starting material. The bis(hexafluorophosphate) was prepared from 2,4′-bipyridyl
a
b
d
and HPF6 in a separate experiment (see Materials of Experimental Section). Commercially available formic acid was used without
further purification. e Quantitative yield.
Ta ble 2. Con tr olled F lu or in a tion of
2-Acetylcycloh exa n on e (15)a
Sch em e 2
reaction yield (%)
run
“F+” (mmol)
2,2′-isomer 1a (0.5)
2,4′-isomer 7a (0.5)
3,3′-isomer 8a (0.5)
4,4′-isomer 9a (0.5)
timeb
of 16c
1
2
3
4
5
<5 min
2 h
85
78
70
87
79
5 h
5 h
bipyridyl and BF3 was noted to very poorly soluble in
acetonitrile. Bis(hexafluorophosphate) and bis(hexafluo-
roantimonate) 7c and 9d were synthesized using HPF6
and SbF5, respectively (runs 10 and 11).
N-fluoropyridinium triflate (14) (1) 19 h
15 (1 mmol) was allowed to react with “F+” (0.5 or 1 mmol) in
a
acetonitrile under reflux, and the reaction was traced by checking
b
with a paper absorbing aqueous KI solution. Each reaction time
The higher homologues, N,N′,N′′-trifluoro-terpyridin-
ium salt 10 and poly(N-fluoropyridinium salt) 11, were
produced quantitatively by the fluorination of terpyridine
and polypyridine,18 respectively, using SbF5 in acetoni-
trile.
was the time when “F+” was consumed, except for run 5 where
“F+” was not completely consumed. c Yields were determined by
19F NMR and calculated on the basis of 15.
F lu or in a tion Rea ctivity of Isom er ic N,N′-Diflu o-
r obip yr id in iu m Sa lts. Relative reactivity was deter-
mined as 2,2′- (1a ) . 2,4′- (7a ) > 3,3′- (8a ) ≈ 4,4′-isomer
(9a ) . N-fluoropyridinium triflate (14) by the controlled
reaction of 0.5 mmol of triflate (1a , 7a , 8a , or 9a ) or 1
mmol of 14 with 1 mmol of 2-acetylcyclohexanone (15)
to give fluoro product 16 shown in Table 2 and Figure 2.
Table 2 shows the reaction time required for consuming
N,N′-difluorobipyridinum triflate at reflux temperature,
and Figure 2 shows the formation curves (vs time) of 16
by reactions at 50 °C. The lowest reactivity noted for
the 4,4′-isomer as a bipyridinium salt indicates the
π-electron conjugation effect to be unessential for fluo-
rination, since the 4,4′-dipyridinium salt may exert strong
π-electron conjugation effect.20 This would explain why
2,2′-isomer 1a reacted more rapidly (<5 min) than any
P r op er ties of N,N′-Diflu or obip yr id in iu m Sa lts.
N,N′-Difluorobipyridinium salts substituted or unsub-
stituted with electron-donating groups are stable non-
hygroscopic crystalline solids. The salts substituted with
electron-withdrawing groups, 3, 5, and 6, are moisture-
sensitive solids. Thus, it was not possible to obtain
dichloro, bis(trifluoromethyl), and bis(COOCH3) deriva-
tives 3b, 5d , and 6a , as pure crystals for elemental
analysis. Tetrafluoroborate 1b was hydrolyzed in boiling
water for 2 h to give 3,3′-dihydroxy derivative 12, which
was isolated in 80% yield as diacetate 13 by treatment
with acetic anhydride (Scheme 2). The alkaline hydroly-
sis of 1b occurred readily at room temperature and was
complete at 1 h. Dihydroxy 12 was isolated as diacetate
13 in 23% yield from the reaction mixture, and other
products were not characterized. Hydrolysis product 12
formation should occur via the carbene mechanism
previously proposed for the novel base-initiated decom-
position of N-fluoropyridinium salts.5f,19
(19) (a) Umemoto, T.; Tomizawa, G. Tetrahedron Lett. 1987, 28,
2705. (b) Umemoto, T.; Tomizawa, G. J . Org. Chem. 1989, 54, 1726.
(c) Umemoto, T.; Tomizawa, G.; Hachisuka, H.; Kitano, M. J . Fluorine
Chem. 1996, 77, 161.
(20) (a) Summers, L. A. Adv. Heterocyc. Chem. 1984, 35, 281. (b)
Hanson, P. Adv. Heterocyc. Chem. 1979, 25, 205. (c) Arai, S.; Hida, M.
Adv. Heterocyc. Chem. 1995, 55, 261.
(18) Yamamoto, T.; Ito, T.; Kubota, K. Chem. Lett. 1988, 153.

3382 J . Org. Chem., Vol. 63, No. 10, 1998
Umemoto et al.
fluorine chemical shift at 39.6 ppm. Fluorination by the
two N-F moieties thus clearly occurs in a step-by-step
manner through 17, and the reactivity difference between
the first and second fluorinations was very small, since
final 18 formed even in the presence of starting 1a . Thus,
17 still retains adequate fluorinating capacity because
the resulting N-hydropyridinium moiety exerted a fairly
strong electron-withdrawing effect. This is also indicated
by the formation curve of 16 using 1a shown in Figure
2, which may be regarded as being due to a single
reaction.
The step-by-step reaction of the N,N′-difluorobipyri-
dinium salt system is in sharp contrast to the N,N′-
difluoro-1,4-diazoniabicyclo[2.2.2]octane salt system in
which one N-F moiety functions as a fluorinating agent
and the other activates the fluorination; once fluorination
occurs by the former, the other N-F moiety immediately
decomposes through intramolecular one-electron
transfer.12a
F lu or in a tion of Nu cleop h iles by N,N′-Diflu or o-
2,2′-bip yr id in iu m Bis(tetr a flu or obor a te) (1b). As-
sessment was made of the reactivity of 2,2′-isomeric
tetrafluoroborate 1b toward various nucleophiles, since
1b is cheap and can be easily prepared. Table 3 shows
1b to be widely useful as an electrophilic fluorinating
agent of diketones, keto esters, ketones, activated aro-
matics, styrenes, vinyl esters, enol trialkylsilyl ethers,
and others in fair to high yields.
F igu r e 2. Formation curves of fluoro diketone 16 by the
fluorination of diketone 15 with 1a , 7a , 8a , 9a , or 14 in CD3CN
at 50 °C. The formation of 16 was monitored by 19F NMR (see
Experimental Section).
Sch em e 3
The reaction of tetrafluoroborate 1b with 15 was slow
(3 h, reflux) due to low solubility (run 1 in Table 3)
compared to that of triflate 1a (run 1 in Table 2). That
of 1b was greatly accelerated following the addition of a
catalytic amount of sodium triflate and was complete at
only 10 min to give 82% of 16 (run 2 in Table 3). An
explanation for this would be the phase transfer of N,N′-
difluorobipyridinium cations by sodium triflate from a
solid to a liquid phase, since triflate 1a is soluble in the
solution. γ-Butyrolactone and formic acid dissolved 1b,
which thus rapidly reacted with 15 in these solvents; the
reaction at 80 °C for 5 min in γ-butyrolactone and at
reflux temperature for <5 min in formic acid gave 77 and
75% of 16, respectively.
N-Chloromethyl-N′-fluoro-1,4-diazoniabicyclo[2.2.2]-
octane bis(tetrafluoroborate) (F-TEDA-BF4) (1 mmol),
available commercially, reacted with 15 (1 mmol) under
the similar conditions (1.5 h, reflux in 2 mL of acetoni-
trile) to give 16 in 83% yield. From this, the reactivity
of 1b is of the same order as that of F-TEDA-BF4.
The difluorination of dibenzoylmethane in acetonitrile
was accelerated by a catalytic amount of triflic acid (run
3). The reaction in formic acid (65 °C, 3 h) without triflic
acid gave a 1:1 mixture of mono- and difluorides in 88%
yield. 1b failed to react with diethyl malonate. Activated
aromatics were smoothly fluorinated by 1b (runs 6-11)
and even more so with a catalytic amount of sodium
triflate (run 7). Resorcinol was fluorinated at the 4- or
6-position in good yield. Methylstyrene was smoothly
fluorinated with 1b (run 12), while styrene fluorination
was difficult. Fluorination of 2-tetralone gave 1-fluoro-
2-tetralone (run 13), and that of 1-tetralone gave a 6.3:1
mixture of 2-fluoro- and 2,2-difluoro-1-tetralone in 44%
yield (reflux, 16 h).
other isomer to give 85% of 16, while 3,3′- and 4,4′-
isomers 8a and 9a reacted the most slowly (5 h). The
single pyridinium ring salt 14 also reacted slowly (19 h).
Fluorinating capacity was previously shown to be cor-
related to the acidity (pKa) of nitrogen lone pairs of the
original pyridines.5d The relative reactivity order is thus
consistent with pKa of bipyridyls, as follows; 2,2′-bipyridyl
(pKa1 ) -0.2) . 4,4′-bipyridyl (pKa1 ) 2.69) . pyridine
(pKa ) 5.42).21 The highest reactivity of the 2,2′-isomer
would thus be due to the N-F moieties being the most
deficient in electrons, and the high capacity of the N,N′-
difluorobipyridinium salt system compared to that of the
N-fluoropyridinium salt system (14) should derive from
the strong electron-withdrawing effect of other N-fluo-
ropyridinium moieties.
The two N-F moieties of all N,N′-difluorobipyridinium
salt isomers were found to be effective for fluorination;
the yields in runs 1-4 in Table 2 exceeded 50%, using a
half equimolar amount of an N,N′-difluorobipyridinium
salt.
As shown in Scheme 3, when 15 (1 mmol) reacted with
1a (1 mmol) for a short time (5 min), the reaction mixture
consisted of fluoro product 16 (0.69 mmol, 69%), mono
N-F intermediate 17 (0.72 mmol, 72%), 18 (0.10 mmol,
1
10%), and 1a (0.19 mmol, 19%), according to 19F and H
NMR analysis. The structure of intermediate 17 was
assigned on the basis of the characteristic N-F moiety
The vinyl acetate of steroid 23 was fluorinated by 1b
to give 6-fluoride 24 in high yield (run 14) when done in
the presence of sodium bicarbonate as an acid trap,
without which, the yield of 24 was decreased, since 24
(21) Kagaku Binran, Kiso-hen; 4th ed.; Chemical Society J apan;
Maruzen Ltd.: Tokyo, 1993; p 320.

Synthesis of N,N′-Difluorobipyridinium and Related Salts
J . Org. Chem., Vol. 63, No. 10, 1998 3383
Ta ble 3. F lu or in a tion of Va r iou s Nu cleop h iles w ith N,N′-Diflu or o-2,2′-bip yr id in iu m Bis(tetr a flu or obor a te) (1b)
a
In all runs, each reaction mixture was stirred under N2. For runs 1, 2, and 4-13, the reaction was carried out in 2 mL of a solvent
using 1.0 mmol of a nucleophile and 0.5 mmol of 1b; for run 3, the reaction was carried out in 2 mL of a solvent using 0.5 mmol of a
nucleophile and 0.5 mmol of 1b; for run 14, the reaction was carried out in 1 mL of a solvent using 0.5 mmol of a nucleophile and 0.25
b
mmol of 1b; for run 15, the reaction was carried out in 2 mL of CH3CN using 0.5 mmol of a nucleophile and 0.25 mmol of 1b. Determined
by 19F NMR using fluorobenzene as an internal standard, based on the amount of a nucleophile used, unless otherwise noted. c Lerman,
O.; Rozen, S. J . Org. Chem. 1983, 48, 724. Reference 5d. e Kitazume, T.; Kobayashi, T. J . Fluorine Chem. 1986, 31, 357. f Chambers, R.
d
g
D.; Greenhall, M. P.; Hutchinson, J . Tetrahedron 1996, 52, 1. The yields were calculated on the basis of the nucleophiles consumed. The
h
conversions of the nucleophiles were 82, 80, 85, 88, and 79% for runs 6, 7, 8, 9, and 10, respectively. Patrick, T. B.; Darling, D. L. J . Org.
Chem. 1986, 51, 3242. i The separation of 4,6-difluororesorcinol and 2-fluororesorcinol by column chromatography on SiO2 was unsuccessful.
j
k
l
m
Staver, S.; Zupan, M. J . Org. Chem. 1985, 50, 3609. The ratio of diastereoisomers was 1/1. Reference 11e. Hesse, R. H. Isr. J . Chem.
1978, 17, 60. A 1:1.7 mixture of 6R- and 6â-fluoro steroids. o A 1:1.4 mixture of 6R- and 6â-fluoro steroids. Reference 6.
n
p
underwent dehydrofluorination due to the resultant
acidic conditions. The enol triethylsilyl ether 25 was
fluorinated in good yield under similar conditions (run
15).
Con clu sion
Dimeric N,N′-difluorobipyridinium and the related
salts were synthesized in high yields and, compared to

3384 J . Org. Chem., Vol. 63, No. 10, 1998
Umemoto et al.
ditional pure 7b (15%). For run 10, the reaction mixture was
filtered, its filtrate was evaporated to dryness under reduced
pressure, and the residue was washed with EtOAc to give pure
7c. For run 12, the reaction mixture was evaporated to
dryness under reduced pressure, and the resulting oil was
washed with MeOH/Et2O and recrystallized from CH3CN/Et2O
to give pure 2b. For runs 13, 14, and 16, to the reaction
mixture were added 3, 6, and 10 mL of Et2O, and the resulting
precipitate was collected by filtration and washed with Et2O
in a drybox to give 3b, 4b, and 6a , respectively. For run 15,
the reaction mixture was evaporated to dryness under reduced
pressure, and the residue was washed with Et2O in a drybox
to give 5d . For runs 17 and 18, the reaction mixture was
evaporated to dryness under reduced pressure, and the residue
was washed with Et2O to give pure 10 and 11, respectively.
Ca u tion . Since F2 is a highly oxidizing and toxic gas, any
experimenter should know the precautions necessary for the
safe handling of F2.5e
the monomeric N-fluoropyridinium salt, were found to
have a high fluorinating capacity due to the electron-
withdrawing effect of the N-F moieties. The 2,2′-isomer
was found to be the most potent fluorinating agent, of
which both N-F moieties were effective for fluorination.
N,N′-Difluoro-2,2′-bipyridinium bis(tetrafluoroborate) (1b)
is thus shown to be the fluorinating agent most useful
for producing fluoro compounds, because of the high
effective fluorine content, the ease of handling, wide
application, and the simple one-batch process from 2,2′-
bipyridyl which has been produced commercially on a
large scale.
Exp er im en ta l Section
Gen er a l. 1H and 19F NMR spectra were recorded at 200
or 500 MHz and 188 or 470 MHz, respectively. The solvents
N,N′-Diflu or o-2,2′-bip yr id in iu m bis(tr iflu or om eth a n e-
su lfon a te) (1a ): mp 190-193 °C (CH3CN-Et2O); 1H NMR
(CD3CN) δ 8.74-8.58 (4 H, m), 9.01 (2H, dt, J ) 7.9, 1.0 Hz),
9.70 (2H, ddd, J ) 16.1, 7.0, 1.0 Hz); 19F NMR 44.0 (2F, brs,
N-F), -78.0 (6F, s, CF3); IR (Nujol) 3063, 1277, 1157, 1032
cm-1. Anal. Calcd for C12H8F8N2O6S2: C, 29.28; H, 1.64; N,
5.69. Found: C, 29.21; H, 1.41; N, 5.63.
1
for 19F NMR were same as those for H NMR, unless otherwise
noted. The 19F chemical shifts were given in ppm downfield
from CFCl3 as an internal standard. IR spectra of the Nujol
method were measured using NaCl plates. The previously
reported apparatus was used for the fluorination.5c,e A poly-
(tetrafluoroethylene) flask was used for the experiments in
which 60% aqueous HPF6 was used. The melting and
decomposition points were uncorrected.
N,N′-Diflu or o-2,2′-bip yr id in iu m Bis(tetr a flu or obor a te)
1
(1b): mp 166.6-167.7 °C (CH3CN-Et2O); H NMR (CD3CN)
Ma ter ia ls. A vinyl acetate of steroid and an enol trieth-
ylsilyl ether for runs 14 and 15 in Table 3 were prepared
according to the literature.22 The dihydrogen salt, N,N′-
dihydro-2,4′-bipyridinium bis(hexafluorophosphate), which was
used in run 10 of Table 1, was prepared by mixing 2,4′-
dipyridyl with 2 molar equiv of 60% aqueous HPF6 in aceto-
nitrile; the crystals were obtained by complete evaporation of
the acetonitrile solvent. 3,3′-Bipyridyl23 and polypyridine18
were prepared according to the literature. N-Fluoropyri-
dinium triflate and a BF3/CH3CN solution (16 wt %) were
purchased from Chichibu Onoda Corp. (J apan) and Stella
Chemifa Corp. (J apan), respectively. The solvents used for
reactions were dried by the usual methods before use, and
other commercially available materials were used without
further purification, unless otherwise noted.
Syn th esis of N,N′-Diflu or o-bip yr id in iu m Sa lts. Gen -
er a l P r oced u r e. In each experiment, the amounts of a
bipyridyl, an acid or a metal salt, and a solvent shown in Table
1 were placed in a flask of the fluorination apparatus. The
charged flask was purged with N2 and placed on a cooling bath
at the temperature shown in Table 1. A 10% F2-90% N2 (v/
v) or a 20% F2-80% N2 (v/v) gas mixture was then introduced
just above the surface of the rapidly stirred reaction mixture
at a flow rate of 5-10 mL min-1 per 1 mmol of bipyridyl. The
amounts of F2 used are given in Table 1. After the flow of F2
was stopped, only N2 was passed through the flask at a rate
of 20 mL min-1 for 10 min. For run 10, a mixture of 2.0 mmol
of N,N′-dihydro-2,4′-bipyridinium bis(hexafluorophosphate)
and 0.1 mmol of 2,4′-bipyridyl was used as the starting
material, and the bis(hexafluorophosphate) was prepared and
isolated as crystals in a separate experiment (see Materials).
The posttreatment for runs 1, 2, 4, and 11 were as follows:
each reaction mixture was evaporated to dryness under
reduced pressure, and the residue was washed with EtOAc to
give pure 1a , 7a , 9a , or 9d . For run 3, the reaction mixture
was filtered through Celite to remove the LiF formed, the
filtrate was evaporated to dryness under reduced pressure, and
the residue was washed with EtOAc to give pure 8a . For runs
5-7 and 9, the resulting precipitate was collected by filtration
and washed with CH3CN and EtOAc to give pure 1b and 9b,
respectively. For run 8, the resulting precipitate was collected
by filtration to give pure 7b (71%). In addition, the filtrate
was evaporated to dryness under reduced pressure, and the
residue was recrystallized from CH3CN/EtOAc to give ad-
δ 8.74-8.58 (4H, m), 9.01 (2H, dt, J ) 8, 1 Hz), 9.65 (2H, ddd,
J ) 16, 7, 1 Hz); 19F NMR 43.6 (2F, brs, N-F), -150 (8F, s,
BF4); IR (Nujol) 3126, 1592, 1488, 1281, 1202, 1057 cm-1; MS
(EI) m/z 97 ((M - 2BF4)2+/2). Anal. Calcd for C10H8B2F10N2:
C, 32.66; H, 2.19; N, 7.62. Found: C, 32.46; H, 2.02; N, 7.48.
N,N′-Diflu or o-4,4′-d im eth yl-2,2′-bip yr id in iu m bis(tet-
r a flu or obor a te) (2b): mp 153-160 °C (with dec) (CH3CN-
Et2O); 1H NMR (CD3CN) δ 2.84 (6H, s, CH3), 8.37 (2H, dm, J
) 7 Hz), 8.46 (2H, dd, J ) 6, 3 Hz), 9.41 (2H, dd, J ) 16, 7
Hz); 19F NMR 35.7 (2F, brs, N-F), -149.8 (8F, s, BF4); IR
(Nujol) 3065, 1600, 1488, 1293, 1208, 1078, 1055, 1028, 837,
760 cm-1; MS (FAB) m/z 203 (M+ - F - 2BF4). Anal. Calcd
for C12H12B2F10N2: C, 36.41; H, 3.06; N, 7.08. Found: C, 36.36;
H, 2.85; N, 7.34.
N,N′-Diflu or o-4,4′-d ich lor o-2,2′-bip yr id in iu m bis(tet-
r a flu or obor a te) (3b): mp 136-140 °C (with dec) (CH3CN-
Et2O); 1H NMR (CD3CN) δ 8.66 (2H, ddd, J ) 7.5, 2.8, 1.5 Hz),
8.71 (2H, dd, J ) 5.3, 2.8 Hz), 9.62 (2H, dd, J ) 14.7, 7.5 Hz);
19F NMR 39.3 (2F, s, N-F), -150.7 (8F, s, BF4); IR (Nujol)
3094, 1584, 1280, 1212, 1150, 1052 cm-1
.
N,N′-Diflu or o-4,4′-d ip h en yl-2,2′-bip yr id in iu m bis(tet-
r a flu or obor a te) (4b): mp 127-133 °C (with dec) (CH3CN-
Et2O); 1H NMR (CD3CN) δ 7.68-7.83 (6H, m), 8.02-8.12 (4H,
dm, J ) 8 Hz), 8.78 (2H, dm, J ) 8 Hz), 8.94 (2H, dd, J ) 6,
3 Hz), 9.60 (2H, dd, J ) 15, 8 Hz); 19F NMR 33.9 (2F, brs,
N-F), -149.9 (8F, s, BF4); IR (Nujol) 1590, 1292, 1208, 1071,
1040, 765 cm-1. Anal. Calcd for C22H16B2F10N2: C, 50.82; H,
3.10; N, 5.39. Found: C, 50.14; H, 3.13; N, 6.73.
N,N′-Diflu or o-4,4′-b is(m et h oxyca r b on yl)-2,2′-b ip yr i-
d in iu m bis(h exa flu or oa n tim on a te) (5d ): mp 81 °C; 1H
NMR (CD3CN) δ 4.11 (6H, s), 9.03 (2H, m), 9.09 (2H, dd, J )
5.7, 2.6 Hz), 9.87 (2H, dd, J ) 14.8, 7.1 Hz); 19F NMR 47.7
(2F, brs, N-F), -110 to -133 (12F, m, SbF6); IR (Nujol) 1750,
1303, 1205, 1143, 1018 cm-1
.
N,N′-Diflu or o-5,5′-bis(tr iflu or om eth yl)-2,2′-bip yr id in -
iu m bis(tr iflu or om eth a n esu lfon a te) (6a ): mp 177-183 °C
(with dec); 1H NMR (CD3CN) δ 9.08 (2H, dd, J ) 8, 3 Hz),
9.40 (2H, dm, J ) 8 Hz), 10.42 (2H, dm, J ) 15 Hz); 19F NMR
48.1 (2F, brs, N-F), -61.8 (6F, s, CF3), -77.9 (6F, s, CF3SO2).
N,N′-Diflu or o-2,4′-bip yr id in iu m bis(tr iflu or om eth a n e-
su lfon a te) (7a ): mp 152-155 °C (CH3CN-EtOAc); 1H NMR
(CD3CN) δ 8.48 (1H, m), 8.53 (1H, ddd, J ) 2.0, 7.5, 7.5 Hz),
8.70 (2H, dd, J ) 7.5, 4.2 Hz), 8.90 (1H, dd, J ) 7.5, 7.9 Hz),
9.50 (1H, dd, J ) 7.5, 17.0 Hz), 9.58 (2H, dd, J ) 7.5, 13.6
Hz); 19F NMR 52.8 (1F, brs, N-F), 38.7 (1F, brs, N-F), -78.1
(6F, s, CF3); IR (Nujol) 3033, 1268, 1154, 1034, 641, cm-1. Anal.
Calcd for C12H8F8N2O6S2: C, 29.28; H, 1.64; N, 5.69. Found:
C, 29.17; H, 1.60; N, 5.73.
(22) House, H. O. Modern Synthetic Reactions, 2nd ed.; W. A.
Benjamin, Inc.: Menlo Park, CA, 1972.
(23) Ishikura, M.; Kamada, M.; Terashima, M. Synthesis 1984, 936.

Synthesis of N,N′-Difluorobipyridinium and Related Salts
J . Org. Chem., Vol. 63, No. 10, 1998 3385
N,N′-Diflu or o-2,4′-bip yr id in iu m bis(tetr a flu or obor a te)
(7b): mp 189-191 °C (with dec) (CH3CN-Et2O); 1H NMR
(CD3CN) δ 8.42-8.57 (2H, m), 8.66 (2H, m), 8.90 (1H, m), 9.4-
9.6 (3H, m); 19F NMR 52.6 (1F, brs, N-F), 38.3 (1F, brs, N-F),
-149.8 (8F, s, BF4); IR (Nujol) 3114, 1604, 1580, 1484, 1455,
1432, 1377, 1271, 1256, 1196, 1062, 862 cm-1; MS (FAB) m/z
175 (M+ - F - 2BF4), 154. Anal. Calcd for C10H8B2F10N2: C,
32.66; H, 2.19; N, 7.62. Found: C, 32.76; H, 2.02; N, 7.52.
N,N′-Diflu or o-2,4′-bip yr id in iu m bis(h exa flu or op h os-
anhydride in 6 mL of pyridine for 1 h at 100 °C. The reaction
mixture was poured into 100 mL of cold water. The resulting
precipitate was collected by filtration and dried at 150 °C
under reduced pressure to give 0.649 g (80% from 1b) of 6,6′-
diacetoxy-2,2′-bipyridyl 13.
6,6′-Dia cetoxy-2,2′-bip yr id yl (13): mp 177-188 °C; 1H
NMR (CDCl3) δ 2.39 (6H, s, Ac), 7.11 (2H, d, J ) 8.0 Hz), 7.90
(2H, t, J ) 8.0 Hz), 8.38 (2H, d, J ) 8.0 Hz); IR (KBr) 1754
(CdO) cm-1; MS m/z 272 (M+). Anal. Calcd for C14H12N2O4:
C, 61.76; H, 4.44; N, 10.29. Found: C, 61.73; H, 4.37; N, 10.28.
1
p h a te) (7c): mp 150-159 °C (with dec) (CH3CN-Et2O); H
NMR (CD3CN) δ 8.42-8.55 (2H, m), 8.63 (2H, m), 8.90 (1H,
m), 9.4-9.6 (3H, m); 19F NMR 52.8 (1F, brs, N-F), 38.3 (1F,
brs, N-F), -71.4 (12F, d, J ) 703 Hz, PF6); IR (Nujol) 3121,
Con tr olled F lu or in a tion of 2-Acetylcycloh exa n on e
(15) w ith N,N′-Diflu or o-bip yr id in iu m Tr ifla tes 1a , 7a , 8a ,
9a , or N-F lu or op yr id in iu m Tr ifla te (14). Into a stirred
solution of 1 mmol of 15 in 2 mL of acetonitrile at room
temperature was added 0.5 mmol of either 1a , 7a , 8a , or 9a
or 1 mmol of 14. Each reaction was run at reflux temperature
under nitrogen atmosphere and monitored at intervals by
checking with a KI solution. 1a , 7a , 8a , and 9a were each
consumed at the reaction times shown in Table 2. 14 was not
completely consumed even at 19 h. The yields of product 16
were determined by 19F NMR of the reaction mixture using
fluorobenzene as an internal standard. The results are
summarized in Table 2.
19F NMR Tr a cin g Exp er im en ts of F lu or in a tion of
2-Acetylcycloh exa n on e (15) w ith N,N′-Diflu or o-bip yr i-
d in iu m Tr ifla te 1a , 7a , 8a , or 9a or N-F lu or op yr id in iu m
Tr ifla te (14). To a solution of 0.063 mmol of 1a , 7a , 8a , or
9a or 0.125 mmol of 14 and 0.125 mmol of fluorobenzene in
0.8 mL of CD3CN in a NMR tube was added 0.125 mmol of
15, and the tube was sealed. Each sealed NMR tube was set
in a NMR probe controlled at 50 °C, and each reaction was
monitored at intervals by 19F NMR using fluorobenzene as an
internal standard. The formation curves (vs time) of product
16 are shown in Figure 2.
1445, 1376, 1251, 1207, 1061, 833 cm-1
. Anal. Calcd for
C10H8F14N2P2: C, 24.81; H, 1.67; N, 5.79. Found: C, 25.74;
H, 1.63; N, 5.62.
N,N′-Diflu or o-3,3′-bip yr id in iu m bis(tr iflu or om eth a n e-
su lfon a te) (8a ): mp 129-131 °C (CH3CN-EtOAc); 1H NMR
(CD3CN) δ 8.52 (2H, dd, J ) 7.1, 13.3 Hz), 9.00 (2H, d, J )
7.1 Hz), 9.43 (2H, dd, J ) 6.8, 13.3 Hz), 9.82 (2H, d, J ) 15.2
Hz); 19F NMR 51.2 (2F, m, N-F), -78.0 (6F, s, CF3); IR (Nujol)
1272 1164 1030 cm-1
. Anal. Calcd for C12H8F8N2O6S2: C,
29.28; H, 1.64; N, 5.69. Found: C, 29.28; H, 1.56; N, 5.76.
N,N′-Diflu or o-4,4′-bip yr id in iu m bis(tr iflu or om eth a n e-
su lfon a te) (9a ): mp 205-212 °C (with dec) (CH3CN-Et2O);
1H NMR (CD3CN) δ 8.63 (4H, m), 9.47 (4H, m); 19F NMR 49.5
(2F, brs, N-F), -78.1 (6F, s, CF3); IR (Nujol) 1493, 1461, 1376,
1255, 1143, 1031, 855 cm-1; MS (FAB) m/z 175 (M+ - F -
2CF3SO3), 154. Anal. Calcd for C12H8F8N2O6S2: C, 29.28; H,
1.64; N, 5.69. Found: C, 29.09; H, 1.42; N, 5.50.
N,N′-Diflu or o-4,4′-bip yr id in iu m bis(tetr a flu or obor a te)
1
(9b): mp 178.8-180.5 °C (CH3CN-Et2O); H NMR (CD3CN)
δ 8.61 (4H, m), 9.45 (4H, m); 19F NMR 49.3 (2F, m, N-F),
-149.7 (8F, s, BF4); IR (Nujol) 3113, 1604, 1307, 1256, 1197,
1059, 1028 cm-1; MS (FAB) m/z 175 (M+ - F - 2BF4). Anal.
Calcd for C10H8B2F10N2: C, 32.66; H, 2.19; N, 7.62. Found:
C, 32.84; H, 2.02; N, 7.55.
F lu or in a t ion of Va r iou s Nu cleop h iles w it h N,N′-Di-
flu or o-2,2′-bipyr idin iu m bis(tetr aflu or obor ate) (1b). Gen -
er a l P r oced u r e. Under N2 atmosphere, 1b was added to a
stirred solution of a nucleophile in a solvent. Nucleophiles,
solvents, additives, their amounts, reaction times, tempera-
tures, and presence or absence of the additives are shown in
Table 3. For all runs, 1b was consumed at the reaction times
shown in Table 3. For runs 1-4 and 10-15, the yields were
determined by 19F NMR of the reaction mixture using fluo-
robenzene as an internal standard. For runs 5-9, after 5 mL
of 0.5 M aqueous Na2S2O3 solution was added to the reaction
mixture, the mixture was extracted with Et2O. The extract
was washed with saturated aqueous NaCl solution, dried with
anhydrous MgSO4, and then analyzed by 19F NMR (fluoroben-
zene as an internal standard) and/or GC (tridecane or hepta-
decane as an internal standard). The fluoro products and their
yields are summarized in Table 3.
N,N′-Diflu or o-4,4′-b ip yr id in iu m b is(h exa flu or oa n t i-
m on a te) (9d ): mp 230-255 °C (with dec) (CH3CN-Et2O); 1H
NMR (CD3CN) δ 8.58 (4H, m), 9.44 (4H, m); 19F NMR 49.5
(2F, brs, N-F), -122 (12F, m, SbF6); IR (Nujol) 3118, 1439,
1257, 854 cm-1; MS (FAB) m/z 175 (M+ - F - 2SbF6), 154.
Anal. Calcd for C10H8F14N2Sb2: C, 18.04; H, 1.21; N, 4.21.
Found: C, 18.20; H, 0.94; N, 4.08.
N,N′,N′′-Tr iflu or o-2,2′:6′,2′′-ter p yr id in iu m tr is(h exa flu -
or oa n tim on a te) (10): dec 85-88 °C; 1H NMR (CD3CN) δ 8.73
(2H, m), 8.81 (2H, m), 9.07 (4H, m), 9.38 (1H, t, J ) 8 Hz),
9.73 (2H, ddd, J ) 16, 7, 1 Hz); 19F NMR 44.7 (2F, brs, N-F),
40.7 (1F, brs, N-F), -122 (18F, m, SbF6); IR (Nujol) 3112,
1575, 1498, 1278 cm-1. Anal. Calcd for C15H11F21N3Sb3: C,
18.06; H, 1.11; N, 4.21. Found: C, 19.45; H, 1.41; N, 5.06.
P oly(N-flu or op yr id in iu m h exa flu or oa n tim on a te-2,4-
d iyl) (11): dec 125 °C; 1H NMR (D2SO4) δ 9.24-9.00 (2H, m),
-8.47 (1H, m); 19F NMR (D2SO4) 39.2 (1F, s, N-F), -114 to
-128 (6F, m, SbF6); IR (Nujol) 3648, 1017, 841, 722 cm-1. Anal.
Calcd for C5H3F7NSb: C, 18.10; H, 0.91; N, 4.22. Found: C,
22.01; H, 1.92; N, 7.84.
Hyd r olysis of N,N′-Diflu or o-2,2′-bip yr id in iu m bis(tet-
r a flu or obor a te) (1b). Into 30 mL of water was added with
stirring 3 mmol of 1b at room temperature. The reaction
mixture was stirred at reflux temperature. The resulting
precipitate was collected by filtration and dried at 110 °C
under reduced pressure to give crude 6,6′-dihydroxy-2,2′-
bipyridyl 12: 1H NMR (CDCl3/CD3OD ) 10/1) δ 6.72 (2H, d, J
) 8.6 Hz), 7.17 (2H, d, J ) 7.1 Hz), 7.68 (2H, dd, J ) 8.6, 7.1
Hz). The crude solid 12 was esterificated with 6 mL of acetic
A structural assignment of the products was carried out by
spectral analysis or by comparison with those of authentic
samples. The spectral data agreed with the assigned struc-
tures or the data of authentic samples. In run 10, 4-fluorore-
sorcinol as a main product was separated from other fluoro
products by column chromatography on SiO2, but 4,6-difluoro-
and 2-fluororesorcinol as minor products failed to be separated
from each other. 4,6-Difluororesorcinol as a new compound
was assigned by complete analysis of 500 MHz NMR and GC-
MS: 1H NMR (acetone-d6) δ 6.66 (1H, t, J ) 8.7 Hz), 6.95 (1H,
t, J ) 10.7 Hz), 8.11 (2H, brs); 19F NMR -149.6; Millimass
Found m/z 146.017 47. Calcd for C6H4O2F2 146.017 94.
J O972338Q