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could be obtained and isolated in 45% yield. If the same
reaction was run in a glass vessel, total decomposition of the
starting material to pyridine-2-sulfonyl chloride occurred,
which then reacted with AgF to produce pyridine-2-sulfonyl
Table 1: Reactivity of 3-substituted disulfides 1b,f–h.
fluoride (d =+ 55 ppm). The two-step reaction starting from
F
disulfide 1a (11 g; 0.05 mol) was then successfully scaled up
giving intermediate 2a in 95% yield (21 g) and 52% yield of
3
-substituted disulfide reagent
Reaction products ratio (SF /SF Cl)
3 4
2
-SF -pyridine (3a; 9.5 g) as a colorless volatile liquid with
5
1
9
1 f (R=F)
0/100
35/65
50/50
80/20
a camphoraceous odor. In its F NMR spectrum, the two
1
b (R=Me)
signals attributable to the SF group of 3a appear at
5
1
1
g (R=Cl)
h (R=Br)
d =+ 51.6 ppm (d, 4F, J = 149.6 Hz) and + 77.9 ppm (m, 1F).
After developing suitable conditions for the two-step
transformation of 2,2’-dipyridyl disulfide (1a) into
2
-SF -pyridine 3a, exploration of the scope and possible
Rapid isolation, which included filtration under dry
5
limitations of this route with regard to preparation of
nitrogen pressure and solvent evaporation in vacuo, provided
crude pyridylsulfur chlorotetrafluorides 2a, c, d, and f–i with
purities in the range of 80–95%. Immediately after isolation,
the crude products were transferred into a fluoropolymer vial
for the final fluorination step, which involved reaction with
AgF. The 3-substituted pyridylsulfur chlorotetrafluorides 2b,
j, and k were isolated as mixtures with the corresponding
pyridylsulfur trifluorides and used as is in their reactions with
AgF. The pyridylsulfur trifluorides did not undergo reaction
under these conditions. All chlorine–fluorine exchange reac-
tions were done under an inert atmosphere using AgF
(2 equiv) in a closed, flat-bottomed PFA vial without any
solvent. After addition of the solid AgF, the vial was sealed
and placed onto a hot plate preheated to 60–708C, The
substituted 2-SF -pyridines was initiated. The work of
5
2]
[
Umemoto et al. provided insight regarding aryl ring sub-
stituents that were compatible with the oxidative fluorination
reaction conditions in that work. Such substituents included
Me, tBu, CF , CCl , F, Cl, Br, and NO . Commercial
3
3
2
availability of simple ring-substituted 2,2’-dipyridyl disulfides
or thiols turns out to be quite limited, with compounds being
high priced, when available. Therefore, it was generally
necessary to synthesize the required eleven disulfides 1b–
l (see the Supporting Information).
Disulfides 1c, d, f, g, and h were found to readily form the
respective 2-pyridylsulfur chlorotetrafluorides (Scheme 2).
1
9
progress of the reaction was monitored by F NMR spec-
troscopy until the complete consumption of the starting
material pyridylsulfur chlorotetrafluoride was observed. The
2
-SF -pyridines 3a–k were isolated after partitioning the
5
reaction mixtures between water and CH Cl2 followed by
2
filtration of the inorganic solids and recovering crude material
by evaporation of the CH Cl extracts. Further purification by
2
2
column chromatography eluting with pentane/CH Cl mix-
2
2
tures provided 38–69% yields of the pure 2-SF -pyridine
5
Scheme 2. Synthesis of 2-pyridylsulfur chlorotetrafluorides 2a–m.
derivatives. We believe that the high volatility of
2
-SF -pyridines contributed to the relatively low yields that
5
were obtained (Scheme 3).
Aberrant behavior was detected for 6-methyl-substituted
disulfide 1e, which in addition to 2-pyridylsulfur chlorotetra-
fluoride formation underwent ring chlorination at the
The SF Cl group in pyridines 2l and 2m, which bear
a strong electron-withdrawing substituent in the 5-position,
4
was highly activated towards S Ar reaction with fluoride
N
5
-position. Also, the reactivities of all 3-substituted disulfides,
anions, a process that competed very favorably with the
1
b, i, j, and k were affected to some degree by the steric
desired final Cl–F exchange reaction. Thus, for those SF Cl
4
influence of the substituent in the 3-position. Although
formation of all pyridylsulfur trifluoride intermediates was
generally demonstrated (by F NMR) after few hours of
reaction, the rate of further transformation into the desired
compounds, conversion into the known 2-fluoropyridines
[10]
[11]
4l and 4m was detected, with little or no SF product
5
1
9
being formed (Scheme 4).
Under the same oxidative fluorination conditions,
3,3’-dipyridyl disulfide and 4,4’-dipyridyl disulfide did not
form the corresponding pyridylsulfur chlorotetrafluorides.
3,3’-dipyridyl disulfide readily forms 3-pyridylsulfur trifluor-
ide, which, in the presence of an excess of chlorine in the
reaction mixture, underwent CÀS bond cleavage much faster
2
-pyridyl-SF Cl compounds depended greatly on the size of
4
the substituent. Thus, disulfide 1i, with the smallest ortho-
fluoro substituent, was fully converted into 2-pyridyl-SF Cl 2i
4
after 72 h, with no residual SF -intermediate remaining. With
3
increasing ortho-substituent size (3-F < 3-Me < 3-Cl < 3-Br),
the conversion rate of the pyridylsulfur trifluorides into the
respective pyridylsulfur chlorotetrafluorides decreased
dramatically and could not be improved by increasing the
reaction temperature, adding additional equivalents of KF
than the formation of the more stable 3-pyridylsulfur
chlorotetrafluoride. In case of 4,4’-dipyridyl disulfide, CÀS
bond chlorinolysis is even faster and neither 4-pyridylsulfur
trifluoride nor 4-pyridylsulfur chlorotetrafluoride could be
detected in the reaction mixture. Instead, in both cases
and Cl , or prolonging the reaction time (Table 1).
2
2
82
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 280 –284