Synthesis of N-substituted sulfonamides containing perhalopyridine moiety as bio-active candidates

Article abstract of DOI:10.1016/j.jfluchem.2020.109507

A series of new halogenated aryl sulfonamides, as bio-active candidates, was synthesized from the reaction of the corresponding aryl sulfonamides with pentafluoro- and pentachloropyridines. Surprisingly, unlike aryl sulfonamides, the reaction of sulfamides with pentafluoro- and pentachloropyridines gave unexpected bis-perfluoro(chloro)pyridin-4-ylamines.

Full text of DOI:10.1016/j.jfluchem.2020.109507

Journal Pre-proof
Synthesis of N-substituted sulfonamides containing perhalopyridine
moiety as bio-active candidates
Raziyeh Hosseini, Reza Ranjbar-Karimi, Kazem
mohammadiannejad
PII:
S0022-1139(20)30058-0
DOI:
https://doi.org/10.1016/j.jfluchem.2020.109507
FLUOR 109507
Reference:
To appear in:
Journal of Fluorine Chemistry
Received Date:
Revised Date:
Accepted Date:
1 December 2019
5 March 2020
5 March 2020
Please cite this article as: Hosseini R, Ranjbar-Karimi R, mohammadiannejad K, Synthesis of
N-substituted sulfonamides containing perhalopyridine moiety as bio-active candidates,
Journal of Fluorine Chemistry (2020), doi: https://doi.org/10.1016/j.jfluchem.2020.109507
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Synthesis of N-substituted sulfonamides containing perhalopyridine moiety as
bio-active candidates
Raziyeh Hosseini, Reza Ranjbar-Karimi* and Kazem mohammadiannejad
Department of Chemistry, Faculty of Science, Vali-e-Asr University of Rafsanjan, Rafsanjan 77176, Islamic Republic
of Iran.
Graphical Abstract
Synthesis of N-substituted sulfonamides containing
perhalopyridine moiety as bio-active candidates
*
Raziyeh Hosseini, Reza Ranjbar-Karimi and Kazem
Mohammadiannejad
Department of Chemistry, Faculty of Science, Vali-e-Asr University of Rafsanjan,
Rafsanjan 77176, Islamic Republic of Iran
Highlights


Synthesis of N-substituted sulfonamides containing perhalopyridine moiety
The reaction of pentafluoropyridine with aryl sulfonamides regioselectivity occurs at the 4-
position of pyridine ring by N2 tetrazole ring.

Synthesis of unexpected bis-perfluoro(chloro)pyridin-4-ylamine

Abstract:
A series of new halogenated aryl sulfonamides, as bio-active candidates, was synthesized from the
reaction of the corresponding aryl sulfonamides with pentafluoro- and pentachloropyridines.
Surprisingly, unlike aryl sulfonamides, the reaction of sulfamides with pentafluoro- and
pentachloropyridines gave unexpected bis-perfluoro(chloro)pyridin-4-ylamines.
Keywords: Pentafluoropyridine, Pentachloropyridine, Sulfonamides, Sulfamide, Nucleophilic
Reaction.
1
. Introduction
Heteroaromatics bearing halogen atoms are an essential class of heterocyclic compounds with
potentially various use in organic chemistry, biochemistry, and pharmaceutical chemistry [1-4].
Among them, perfluorinated pyridines have special interest in organic synthesis because they are
suitable precursors for synthesis of substituted perfluoropyridines, ring-fused fluorinated
heterocycles as well as macrocycle compounds, as reflected in numerous research studies
dedicated to their application [5-9]. In the last few years, we investigated the reaction of various
types of ambident nucleophiles as well as equal and unequal bidentate nucleophiles with
perfluorinated compounds because of electron deficient property of such systems [10-15], whereas
nature of nucleophile, solvent and reaction conditions performed determinative role in their
regiochemistry.
Sulfonamides are an important moiety of various range of bioactive molecules and
pharmaceutical compounds such as anticancer, antitumor, protease inhibitory, antibacterial, anti-
inflammatory, and anticonvulsant activities [16-29]. Furthermore, sulfonamides used as an
efficient kind of protective group for amine owing to their facile removal feature [30-32]. On the
other hand, sulfonamides containing fluorinated moiety showed improved biological properties
[
33-40].

Sulfonamides are less nucleophilic than amines due to the electron-withdrawing property of
sulfonyl group attached to amino group. Nevertheless, numerous articles focused on them as
nucleophile groups for construction structures bearing sulfonamide moiety because of importance
such compounds [40-46].
Besides great importance of sulfonamides in the pharmaceutical and agrochemical industries, in
continuity with research on nucleophilic reactions of perhalogenated pyridines, we will to report
the reaction of some sulfonamides with pentafluoropyridine and pentachloropyridine for
preparation of new N-perhalopyridyl sulfonamide derivatives.
2
. Results and discussion
Sulfonamides 3a-h were synthesized by the reaction of aliphatic and aromatic amines with aryl
sulfonyl chlorides 1a-b according to the reported procedure (Scheme 1) [47].
The reaction of pentafluoropyridine 4a with 4-methyl-N-propylbenzenesulfonamide 3a in the
presence of potassium carbonate was applied as a model reaction for optimization of reaction
conditions (Table 1). At room temperature, the reaction was not successful in any of the solvents.
At reflux, the reaction gave high yield in acetonitrile (Table 1, Entry 4), whereas the yields were
low in other solvents. Accordingly, the reaction of pentafluoropyridine 4a with 4-methyl-N-
propylbenzensulfonamide 3a under optimized reaction conditions gave 4-methyl-N-
(
perfluoropyridin-4-yl)-N-propylbenzenesulfonamide 5a after washing of the product with
ethanol (Table 2). The two resonances observed at -88.6 and -142.6 ppm (ortho and meta fluorine
1
9
atoms, respectively) by F NMR analysis indicated replacement of para fluorine atom to nitrogen
1
ring by sulfonamide moiety. H NMR spectrum of this compound showed two doublet peaks at
7
.36 ppm and 7.69 ppm for aromatic hydrogens and a singlet peak at 2.46 ppm for methyl attached
to benzene ring. It also indicated two triplet peaks at 0.87 and 3.47 ppm and one multiplet peak at
1
3
1
.46 ppm for propyl hydrogens. In C NMR spectrum 5a, aromatic carbons were located in the
range of 127.5-144.8 ppm and aliphatic carbons were located in the range of 10.7-51.6 ppm.
Similarly, N-perfluoropyridyl sulfonamides 5b-g were obtained by the reaction of corresponding
1
19
sulfonamides with pentafluoropyridine 4a (Table 2). Interestingly, H NMR analysis as well as F
19
NMR analysis of 5d showed nitrogen inversion phenomenon. For example, F NMR spectrum 5d

revealed two resonances at -99.0 and -102.8 ppm for ortho fluorine atoms and two resonances at -
1
54.5 and -172.3 ppm for meta fluorine atoms.
In order to expand our research, we performed reaction of some sulfonamides with
pentachloropyridine 4b as electron-poor system. Similar to pentafluoropyridine, anion derived
from sulfonamides 3c, 3f and 3g attacked to the 4-position of pyridine ring and produced N-
perchloropyridyl sulfonamides 5h-j in good yields (Table 2).
In contrast with 3d, sulfonamide 3h on treatment with pentafluoropyridine gave N,N-
bis(perfluoropyridin-4-yl)benzenesulfonamide 6 as major product along with N-(perfluoropyridin-
4
-yl)benzenesulfonamide 5k, via attacking the anion derived from product 5k in basic medium to
other molecule of pentafluoropyridine (Scheme 3). The absence of absorption band for NH
stretching in IR spectrum confirmed the structure of product 6, while IR spectrum product 5K
-1
showed a broad absorption band at 3426 cm for NH stretching.
In continuous our research, we performed the reaction of sulfamide 7 as bidentate nucleophile
19
with pentafluoropyridine. The F NMR spectrum of product showed the characteristic bands for
4
-substituted tetrafluoropyridine at -93.1 and -153.2 ppm for ortho and meta fluorine atoms. The
1
13
H NMR spectrum showed a broad peak at 10.77 and the C spectrum showed bands for the ring
carbon atoms which is the characteristic of a 4-substituted tetrafluoropyridine. The elemental
analysis indicated that the product had the molecular formula C10HF
8
3
N . This data suggested that
the compound was bis-(2,3,5,6-tetrafluoro-4-pyridyl)amine 8 (Scheme 4). The structure of
compound 8 was confirmed by X-ray analysis on a single crystal, as shown in Fig. 1. This
compound has been reported previously by a different route [48]. Performance of the reaction
without base failed. We repeated the reaction in the presence of different molar ratios of sulfamide
and pentafluoropyridine in the presence of the corresponding amounts of base, but the result was
the same. Similarly, the reaction of pentachloropyridine 4b and sulfamide 7 with a different molar
ratios and in the presence of potassium carbonate yielded bis(perchloropyridin-4-yl)amine 9
(Scheme 4). A plausible mechanism for formation of 8 is shown in scheme 5. We believe that the
first step is the expected nucleophilic substitution-fluorine by nitrogen of sulfamide, to give the
first formed intermediate A and then, intermediate A is converted to anion B under basic medium
condition of reaction, which attacked another molecule of pentafluoropyridine and gave compound

8
according to a mechanism postulated by Coe and co-workers [48] concerning reactions between
pentafluoropyridine and urea. Compound 9 was obtained in same manner.
3
. Conclusion
In conclusion, we have demonstrated that aryl sulfonamides successfully react with
pentafluoro- and pentachloropyridine to give new N-perhalopyridyl sulfonamides as bio-active
candidates. In contrast with aryl sulfonamides, the reaction of sulfamide with pentafluoro- and
pentachloropyridine gave unexpected bis-perfluoro(chloro)pyridin-4-ylamine.
4
. Experimental
All the solvents and starting materials were obtained commercially (Merck). Solvents were dried
1
using the procedures recommended in the literature and distilled before use. H NMR spectra were
1
3
19
recorded at 500 MHz. C NMR spectra were recorded at 125 MHz. F NMR spectra were
recorded at 470 and 282 MHz. The elemental analyses for C, H, and N were performed using
Heraeus CHN-O rapid analyzer. TLC analysis was performed on silica gel TLC plates (Merck).
Reaction of sulfonamides with perhalopyridines; General procedure
A mixture of sulfonamide 3 or sulfamide 7 (1 mmol) and perhalopyridine 4 (1 mmol) in the
presence of K
was poured on 10 mL water and extracted with chloroform (2× 30 mL), then organic phase dried
over MgSO and solvent evaporated. The pure product was obtained after washing with ethanol.
2
CO
3
(1 mmol) in CH CN (5 mL) was stirred at reflux for 12 h. The reaction mixture
3
4
4
-methyl-N-(perfluoropyridin-4-yl)-N-propylbenzenesulfonamide (5a
)
Yield: 88% (0.32 g); yellow solid; mp 79-86

C. (Found: C, 49.67; H, 3.83; N, 7.70.
C
15
H
14
F
4
N
2
O
2
S requires: C, 49.72; H, 3.89; N, 7.73%). IR (KBr):
cm . H NMR (500 MHz, CDCl ): δ = 7.69 (d, 2H, J = 8.4 Hz, Ar-H), 7.35 (d, 2H, J = 8.51
Hz, Ar-H), 3.47 (t, 2H, J = 7.3 Hz, NCH ), 2.46 (s, 3H, CH ), 1.45 (sext, 2H, J = 7.3 Hz,
CH CH CH ), 0.87 (t, 3H, J = 7.3 Hz, CH ). C NMR (125 MHz, CDCl ): δ = 144.9
Ar-C), 143.7 (dm, J = 234.7 Hz, C2,6-py), 141.0 (dm, J = 262.0 Hz, C3,5-py), 134.6 (Ar-
C), 130.0 (Ar-CH), 127.6 (Ar-CH), 51.6 (NCH ), 21.9 (CH ), 21.6 (CH ), 10.7 (CH CH
, 470.33 MHz): δ = -88.6 (m, 2F, F2,6-py), -142.8 (m, 2F, F3,5-py).

= 1164 and 1361 (SO
2
)
-
1 1
3
2
3
1
3
2
2
3
2
CH
3
3
(
2
3
2
2
3
)
1
9
ppm. F NMR (CDCl
3

N-ethyl-4-methyl-N-(perfluoropyridin-4-yl)benzenesulfonamide (5b
Yield: 85% (0.29 g); yellow solid; mp 57-61 C. (Found: C, 48.17; H, 3.41; N, 7.99.
S requires: C, 48.28; H, 3.47; N, 8.04%). IR (KBr): = 1163 and 1363 (SO
cm . H NMR (500 MHz, CDCl ): δ = 7.71 (d, 2H, J = 8.3 Hz, Ar-H), 7.36 (d, 2H, J =8.2
Hz, Ar-H), 3.56 (q, 2H, J =7.3 Hz, NCH ), 2.47 (s, 3H, CH ), 1.11 (t, 3H, J = 7.2 Hz,
): δ = 144.9 (Ar-C), 143.7 (dm, J = 235.2 Hz, C2,6-
py), 141.1 (dm, J = 264.8 Hz, C3,5-py), 135.5 (Ar-C), 130.0 (Ar-CH), 127.6 (Ar-CH), 45.0
)

C
14
12
H F
4
N
2
O
2

2
)
-
1 1
3
2
3
1
3
CH
2
CH
3
). C NMR (125 MHz, CDCl
3
1
9
(
NCH
2
), 22.0 (CH
3
), 13.9 (CH
2
CH
3
). F NMR (CDCl , 470.33 MHz): δ = -88.5 (m, 2F,
3
F2,6-py), -143.1 (m, 2F, F3,5-py).
N-benzyl-4-methyl-N-(perfluoropyridin-4-yl)benzenesulfonamide (5c
Yield: 75% (0.31 g); white solid; mp 78-88 C. (Found: C, 55.57; H, 3.40; N, 6.78.
S requires: C, 55.61; H, 3.44; N, 6.83%). IR (KBr): = 1170 and 1369 (SO
cm . H NMR (500 MHz, CDCl ): δ = 7.78 (d, 2H, J = 8.3 Hz, Ar-H), 7.40 (d, 2H, J = 8.3
Hz, Ar-H), 7.22-7.24 (m, 3H, Ar-H), 7.18-7.20 (m, 2H, Ar-H), 4.70 (s, 2H, NCH ), 2.50 (s,
): δ = 145.2 (Ar-C), 143.5 (dm, J = 227.4 Hz, C2,6-
py), 140.8 (dm, J = 260.2 Hz, C3,5-py), 135.2 (Ar-C), 133.4 (Ar-C), 130.2 (Ar-CH), 128.9
)

C
19
14
H F
4
N
2
O
2

2
)
-
1 1
3
2
1
3
3
H, CH
3
). C NMR (125 MHz, CDCl
3
1
9
(
Ar-CH), 128.8 (Ar-CH), 128.3 (Ar-CH), 127.7 (Ar-CH), 52.4 (NCH
2
), 22.3 (CH ). F
3
NMR (CDCl , 470.33 MHz): δ = -88.9 (m, 2F, F2,6-py), -142.4 (m, 2F, F3,5-py).
3
4
-methyl-N-(perfluoropyridin-4-yl)benzenesulfonamide (5d
Yield: 70% (0.22 g); white solid; mp 80-97 C. (Found: C, 44.97; H, 2.49; N, 8.73.
S requires: C, 45.00; H, 2.52; N, 8.75%). IR (KBr): = 3442 (NH), 1146 and
): δ = 7.772 and 7.769 (s, 1H), 7.67 (d, J
7.8 Hz, 1.14H, Ar-H), 7.48 (d, J = 6.8 Hz, 0.61H, Ar-H), 7.10 (d, J = 7.9 Hz, 1.19H, Ar-
H), 6.96 (d, J = 7.9 Hz, 0.63H, Ar-H), 2.29 (s, 1.83 H, CH ), 2.25 (s, 0.99H, CH ), The
signal of NH was not observed due to the broadening. C NMR (125 MHz, DMSO-
)

C
12
H
8
F
4
N
2
O
2

-
1 1
1384 (SO
2
) cm . H NMR (500 MHz, DMSO-d
6
=
3
3
1
3
d
1
6
/CDCl
3
): δ = 144.2 (dm, J = 231.0 Hz, C2,6-py), 140.1 (dm, J = 242.5 Hz, C3,5-py),
).
39.3 (Py-C), 128.6 (Ar-CH), 128.3 (Ar-CH), 126.5 (Ar-CH), 125.9 (Ar-CH), 21.3 (CH
3
19F NMR (DMSO, 470.33 MHz): δ = -99.0, -102.8 (m, 2F, F2,6-py), -154.5, -172.3 (m, 2F,
F3,5-py) ppm
.

N-(perfluoropyridin-4-yl)-N-propylbenzenesulfonamide (5e
Yield: 60% (0.21 g); yellow solid; mp 84-88 C. (Found: C, 48.23; H, 3.45; N, 7.98.
S requires: C, 48.28; H, 3.47; N, 8.04%). IR (KBr): = 1166 and 1362 (SO
cm . H NMR (500 MHz, CDCl ): δ = 7.82 (d, 2H, J = 8.2 Hz, Ar-H), 7.68 (t, 1H, J = 7.6
Hz, Ar-H), 7.57 (t, 2H, J = 7.8 Hz, Ar-H), 3.50 (t, 2H, J = 7.4 Hz, N-CH ), 1.47 (sext, 2H,
). C NMR (125 MHz, CDCl ): δ =
43.8 (dm, J = 241.7 Hz, C2,6-py), 142.2 (m, C4-py), 140.9 (dm, J = 256.3 Hz, C3,5-py),
38.3 (Ar-C), 133.8 (Ar-CH), 129.4 (Ar-CH), 127.5 (Ar-CH), 51.7 (NCH ), 21.9
): δ = -88.4 (m, 2F, F2,6-py), -
)

C
14
12
H F
4
N
2
O
2

2
)
-
1 1
3
2
1
3
J = 7.4 Hz, CH
2
CH
2
CH
3
), 0.88 (t, 3H, J = 7.4 Hz, CH
3
3
1
1
2
1
9
(
CH
2
CH
2
CH
3
), 10.6 (CH
3
). F NMR (470.33 MHz, CDCl
3
142.8 (m, 2F, F3,5-py).
N-ethyl-N-(perfluoropyridin-4-yl)benzenesulfonamide (5f
Yield: 80% (0.27 g); white solid; mp 101-116 C. (Found: C, 46.65; H, 2.97; N, 8.35.
S requires: C, 46.71; H, 3.02; N, 8.38%). IR (KBr): = 1164 and 1350 (SO
cm . H NMR (500 MHz, CDCl ): δ = 7.84 (d, 2H, J = 7.6 Hz, Ar-H), 7.68 (t, 1H, J =7.5
Hz, Ar-H), 7.57 (t, 2H, J = 7.6 Hz, Ar-H), 3.61 (q, 2H, J = 7.3 Hz, NCH ), 1.13 (t, 3H, J =
): δ = 145.1 (dm, J = 232.3 Hz, C2,6-py), 142.3
dm, J = 251.6 Hz, C3,5-py), 138.6 (Py-C), 138.5 (Ar-C), 133.8 (Ar-CH), 129.4 (Ar-CH),
)

C
13
10
H F
4
N
2
O
2

2
)
-
1 1
3
2
1
3
7.3 Hz, CH
3
). C NMR (125 MHz, CDCl
3
(
1
9
1
2
27.0 (Ar-CH), 44.7 (NCH
2
), 13.92 (CH
3
). F NMR (CDCl , 470.33 MHz): δ = -88.3 (m,
3
F, F2,6-py), -143.1 (m, 2F, F3,5-py).
N-benzyl-N-(perfluoropyridin-4-yl)benzenesulfonamide (5g
Yield: 70% (0.28 g); yellow solid; mp 95-97 C. (Found: C, 54.50; H, 3.08; N, 7.00.
S requires: C, 54.55; H, 3.05; N, 7.07%). IR (KBr): = 1172 and 1355 (SO
cm . H NMR (500 MHz, CDCl ): δ = 7.89 (d, J = 7.4 Hz, 2H, Ar-H), 7.73 (t, J = 7.4 Hz,
H, Ar-H), 7.62 (t, J = 7.8 Hz, 2H, Ar-H), 7.23 – 7.27 (m, 3H, Ar-H), 7.17-7.20 (m, 2H,
)

C
18
12
H F
4
N
2
O
2

2
)
-
1 1
3
1
1
3
Ar-H), 4.71 (s, 2H, NCH
2
). C NMR (125 MHz, CDCl ): δ = 152.7(Ar-C), 143.5 (dm, J =
3
2
1
43.4 Hz, C2,6-py), 140.8 (dm, J = 263.8 Hz, C3,5-py), 134.0 (Ar-CH), 133.3 (Ar-C),
1
9
30.0 (Ar-CH), 128.9 (Ar-CH), 128.3 (Ar-CH), 127.7 (Ar-CH), 51.3 (NCH
2
). F NMR
(CDCl
3
, 470.33 MHz): δ = -88.7 (m, 2F, F2,6-py), -142.4 (m, 2F, F3,5-py).
N-benzyl-4-methyl-N-(perchloropyridin-4-yl)benzenesulfonamide (5h
)

Yield: 75% (0.36 g); white solid; mp 109-110
S requires: C, 47.92; H, 2.96; N, 5.88%). IR (KBr):
cm . H NMR (500 MHz, CDCl ): δ = 7.80 (d, 2H, J = 8.3 Hz, Ar-H), 7.36 (d, 2H, J = 7.8
Hz, Ar-H), 7.25 (t, 1H, J = 7.2 Hz, Ar-H), 7.20 (t, 2H, J = 7.2 Hz, Ar-H), 7.16 (d, 2H, J =

C. (Found: C, 47.81; H, 2.87; N, 5.85.
C
19
H14Cl
4
N
2
O
2

= 1168 and 1360 (SO
2
)
-
1 1
3
1
3
7
1
1
.2 Hz, Ar-H), 4.75 (s, 2H, NCH
2
), 2.49 (s, 3H, CH
3
). C NMR (125 MHz, CDCl ): δ =
3
47.0 (Ar-C), 146.2 (Ar-C), 144.3 (Ar-C), 136.7 (Ar-C), 133.1 (Ar-CH), 132.8 (Ar-C),
29.82 (Ar-CH), 129.78 (Ar-CH), 128.9 (Ar-CH), 128.5 (Ar-CH), 128.1 (Ar-CH), 122.7
(
Ar-C), 53.5 (NCH
2
), 22.3 (CH ) ppm.
3
N-ethyl-N-(perchloropyridin-4-yl)benzenesulfonamide (5i
Yield: 87% (0.35 g); white solid; mp 114-116 C. (Found: C, 39.00; H, 2.50; N, 6.93.
S requires: C, 39.03; H, 2.52; N, 7.00%). IR (KBr): = 1170 and 1356 (SO
cm . H NMR (500 MHz, CDCl ): δ = 7.88 (d, 2H, J = 7.1 Hz, Ar-H), 7.65 (t, 1H, J = 7.4
Hz, Ar-H), 7.55 (t, 2H, J = 7.8 Hz, Ar-H), 3.68 (q, 2H, J = 7.3 Hz, NCH ), 1.15 (t, 3H, J =
): δ = 147.2 (Ar-C), 146.5 (Ar-C), 139.8 (Ar-C),
33.5 (Ar-CH), 133.2 (Ar-C), 129.2 (Ar-CH), 127.8 (Ar-CH), 45.6 (NCH ), 14.1 (CH ).
)

C
13
H10Cl
4
N
2
O
2

2
)
-
1 1
3
2
1
3
7
1
.3 Hz, CH
3
). C NMR (125 MHz, CDCl
3
2
3
N-benzyl-N-(perchloropyridin-4-yl)benzenesulfonamide (5j
Yield: 82% (0.38 g); yellow solid; mp 110-111 C. (Found: C, 46.69; H, 2.51; N, 5.94.
S requires: C, 46.78; H, 2.62; N, 6.06%) IR (KBr): = 1165 and 1357 (SO
cm . H NMR (500 MHz, CDCl ): δ = 7.92 (d, 2H, J = 8.3 Hz, Ar-H), 7.68 (t, 1H, J = 7.5
Hz, Ar-H), 7.58 (t, 2H, J = 7.8 Hz, Ar-H), 7.24-7.27 (m, 1H, Ar-H), 7.21 (t, 2H, J = 7.8 Hz,
)

C
18
H12Cl
4
N
2
O
2

2
)
-
1 1
3
1
3
Ar-H), 7.16 (d, 2H, J = 8.1 Hz, Ar-H), 4.78 (s, 2H, NCH
δ = 147.0 (Ar-C), 146.0 (Ar-C), 139.9 (Ar-C), 133.7 (Ar-CH), 133.1 (Ar-C), 132.7 (Ar-C),
29.8 (Ar-CH), 129.3 (Ar-CH), 128.9 (Ar-CH), 128.5 (Ar-CH), 128.0 (Ar-CH), 52.0
NCH ).
2
). C NMR (125 MHz, CDCl ):
3
1
(
2
N-(perfluoropyridin-4-yl)benzenesulfonamide (5k
Yield: 45% (0.14 g); white solid; decomposed at 290
S requires: C, 43.14; H, 1.97; N, 9.15%). IR (KBr): 
)

C. (Found: C, 43.09; H, 1.87; N,
= 3426 (NH), 1165
): δ = 7.72-7.74 (m, 2H, Ar-H), 7.39-
7
.10. C11
H
6
F
4
N
2
O
2
-
1 1
and 1384 (SO
2
) cm . H NMR (500 MH
z
, DMSO-d
6

1
3
7
2
1
.43 (m, 3H, Ar-H) ppm; C NMR (125 MHz, DMSO-d
6
): δ 147.7 (Ar-C),144.4 (dm, J =
38.6 Hz, C2,6-py), 141.9 (m, C4-py), 135.5 (dm, J = 257.3 Hz, C3,5-py), 130.2 (Ar-CH),
1
9
28.5 (Ar-CH), 125.8 (Ar-CH). F NMR (470 MHz, DMSO,): δ = -99.0 (m, 2F, F2,6-py),
-
154.5 (m, 2F, F3,5-py).
N,N-bis(perfluoropyridin-4-yl)benzenesulfonamide (
Yield: 50% (0.23 g); white solid; mp 150-156 C. (Found: C, 42.17; H, 1.05; N, 9.15.
S requires: C, 42.21; H, 1.11; N, 9.23%). IR (KBr): = 1164 and 1300 (SO
cm . H NMR (500 MHz, DMSO-d ): δ = 7.73-7.75 (m, 2H, Ar-H), 7.41-7.43 (m, 3H, Ar-
H). The signal of NH was not observed due to the broadening. C NMR (125 MHz, DMSO-
): δ = 147.7 (Ar-C), 144.4 (dm, J = 233.9 Hz, C2,6-py), 141.8 (m, C4-py), 137.6 (dm, J
6)

C
16
5
H F
8
N
3
O
2

2
)
-
1 1
6
1
3
d
6
1
9
=
258.3 Hz, C3,5-py), 130.2 (Ar-H), 128.5 (Ar-CH), 125.8 (Ar-CH). F NMR (470 MHz,
DMSO): δ = -89.3 (m, F2,6-py), -153.9 (m, F3,5-py).
bis(perfluoropyridin-4-yl)amine (
8)
4
8
Yield: 75% (0.24 g); white solid; mp 143-145

C (144-146 C) . (Found: C, 38.14; H,
0.41; N, 13.25. C10HF
8
N
3
requires: C, 38.11; H, 0.32; N, 13.33%). IR (KBr):  3306 (NH)
-
1 1
13
cm . H NMR (500 MHz, DMSO-d ): δ = 10.77 (s, 1H, NH). C NMR (125 MHz, DMSO-
6
6
d ): δ = 143.5 (dm, J = 235.4 Hz, C2,6-py), 135.2 (dm, J = 253.9 Hz, C3,5-py), 132.8 (m,
1
9
C4-py). F NMR (282 MHz, DMSO-d
py).
6
) δ = -93.1 (m, 2F, F2,6-py), -153.2 (m, 2F, F3,5-
bis(perchloropyridin-4-yl)amine (
yield 45% (0.20 g); white solid; mp 147-150
requires: C, 26.89; H, 0.23; N, 9.41%). IR (KBr):
9)

C (Found: C, 26.78; H, 0.15; N, 9.34.
-
1 1
C
10HCl
8
N
3

3386 (NH) cm . H NMR
): δ = 7.38 (s, 1H, NH). C NMR (125 MHz, DMSO-d ): δ = 151.3
C2,6-py), 144.6 (Hz, C3,5-py), 112.1 (m, C4-py).
1
3
(500 MHz, DMSO-d
6
6
(
Declaration of interests
The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.

Acknowledgment
The authors wish to thank Vali-e-Asr University of Rafsanjan for partially funding this work.

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Fig. 1. The molecular structure of 8
Scheme 1. Synthesis of sulfonamides 3a-h
Scheme 3. The reaction of sulfonamide 3h with pentafluoropyridine

Scheme 4. The reaction of sulfamide with pentafluoro- and pentachloropyridine
Scheme 5. Proposed explanation for the formation of 8

Table 1: Effect of solvent and temperature on the reaction of pentafluoropyridine 4a and
-methyl-N-propylbenzensulfonamide 3a
4
Entry
Solvent
THF
Temperature Time (h)
Yield (%)
1
2
3
4
5
6
7
8
r.t.
12
15
10
12
12
17
12
13
trace
THF
reflux
r.t.
40
CH
CH
3
3
CN
CN
trace
reflux
r.t.
88
EtOH
n.r.
EtOH
reflux
r.t.
30
Acetone
Acetone
trace
reflux
20
a
Reaction conditions: 4a (1.0 mmol), 3a (1.0 mmol), K
2
CO
3
(1.0 mmol), solvent (5.0 ml).

Table 2: Synthesis of N-perfluoropyridyl sulfonamides and N-perchloropyridyl sulfonamides