Reactions of pentafluoropyridine with amidoximes

Article abstract of DOI:10.1007/s13738-017-1174-1

Abstract: In this paper, site reactivity of amidoximes with pentafluoropyridine under basic conditions in dry CH₃CN was investigated. The aromatic nucleophilic substitution of pentafluoropyridine with amidoximes occurs in the 4-position of the

Full text of DOI:10.1007/s13738-017-1174-1

J IRAN CHEM SOC
DOI 10.1007/s13738-017-1174-1
ORIGINAL PAPER
Reactions of pentafuoropyridine with amidoximes
Reza Ranjbar‑Karimi1 · Asma Karbakhsh‑Ravari1 · Alireza Poorfreidoni1
Received: 20 December 2016 / Accepted: 1 August 2017
© Iranian Chemical Society 2017
Abstract In this paper, site reactivity of amidoximes with
pentafuoropyridine under basic conditions in dry CH3CN
was investigated. The aromatic nucleophilic substitution
of pentafluoropyridine with amidoximes occurs in the
4-position of the pyridine ring by the oxygen site of ami-
doximes and followed by reaction of other sites, depend-
ing on reaction conditions. Substituted imidamide systems
4a–g were readily accessed using a 1:1 molar ratio of
pentafuoropyridine and amidoximes in concentrated ace-
tonitrile and in refux condition for 6 h, while reaction of
pentafuoropyridine with amidoximes in 1:1 molar ratio and
in diluted acetonitrile under refux condition for 24 h gave
novel pyridooxadiazine system 4h, i. Pentafuoropyridine
reacts also with amidoximes in 2:1 molar ratio under dry
conditions to aford the bis-perfuoropyridyl imidamide sys-
tems 4j, k.
* Reza Ranjbar-Karimi
r.ranjbarkarimi@vru.ac.ir; Karimi_r110@yahoo.com
1
Department of Chemistry, Faculty of Science, Vali-e-Asr
University, Rafsanjan 77176, Islamic Republic of Iran
Vol.:(0123456789)
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J IRAN CHEM SOC
Graphical Abstract
Reactions of pentafluoropyridine with amidoximes
*
Reza Ranjbar-Karimi , Asma Karbakhsh-Ravari, Alireza Poorfreidoni
Department of Chemistry, Faculty of Science, Vali-e-Asr University, Rafsanjan 77176, Islamic
Republic of Iran
of reaction of various nucleophiles with perhalopyridines
[13]. We have shown that enolate anion derived from
ketones selectively reacts from the oxygen site with pen-
tafuoropyridine. This selectivity was explained on the
basis of hard–hard interaction principle [14]. Previously,
we have investigated the reaction of pentafuoropyridine
and pentachloropyridine with nitrogen- and oxygen-cen-
tered difunctional nucleophiles derived from formamides
and demonstrated that two systems can successfully react
with enol imines from both oxygen and nitrogen site,
depending on the substituent located on the benzene ring
of formamide [15, 16]. Polyhalogenated pyridines are use-
ful building block for the synthesis of other heterocyclic
systems. Ring-fused systems such as pyrido[3,4-b]pyra-
zine [17], imidazopyridine [18] and dipyrido[1,2-a;3′,4′-d]
imidazole systems [7] have been synthesized from the
reaction of pentafuoropyridine with nitrogen difunctional
nucleophiles. Previously, we have shown that the ring-
fused systems can be successfully synthesized from the
reaction of some bidentate nucleophiles with perfuoro-
pyridines [16, 19].
Keywords Pentafuoropyridine · Amidoxime ·
Heterocycle · Synthesis · Pyridooxadiazine
Introduction
Heteroaromatic systems are very applicable compounds in
organic chemistry, and most of the pharmaceuticals, materi-
als and life science products are heterocyclic derivatives [1,
2]. An important class of heterocyclic compounds is poly-
substituted pyridines with wide applications in biochemis-
try, organic chemistry and pharmaceutical chemistry [3–6].
These heterocycles, especially perfuorinated derivatives, are
highly electron-defcient species and therefore susceptible to
nucleophilic attack due to the presence of high electronega-
tive fuorine atoms [1, 7]. An important feature of highly
fuorinated pyridines is the displacement of fuorine atoms
located at the ortho, para or meta positions of the pyridine
ring by nitrogen-, oxygen- and sulfur-centered nucleophiles
[8–11].
Reactions of pentafuoropyridine mainly involved in the
nucleophilic substitution processes, and many researches
have been carried out on the reaction of pentafuoropyri-
dine with various nucleophiles [1, 12]. The regiochem-
istry of the reactions has been afected by the nature of
nucleophile, reaction condition and the solvent. During the
last few years, we have been studying the regiochemistry
Banks and co-worker have been reported the synthesis
of O-tetrafuoropyridyl oximes arising from monosubstitu-
tion at both 2- and 4-positions, by the reaction of sodium
oximates with pentafuoropyridine [20]. Recently, perfuo-
ropyridin-4-yloxy amino compounds were synthesized
from the reaction of pentafuoropyridine with oximes [21].
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J IRAN CHEM SOC
Amidoximes are an important class of organic com-
pounds with great pharmaceutical and biochemical activi-
ties [22, 23] that widely used as intermediates in organic
synthesis, such as the synthesis of polynuclear complexes
(clusters) and heterocycles [24, 25].
C, 43.4; H, 2.8; N, 16.9%). IR (KBr): νmax 3499, 3362
1
(NH2), 1631 (C=N) cm−1. H-NMR (300 MHz, DMSO-
d6): δH 6.51 (bs, 2H, NH2), 1.40 (m, 1H, CH-cyclopro-
pyl), 1.72–0.76 (m, 4H, CH2-cyclopropyl) ppm. 13C-NMR
(75 MHz, DMSO-d6): δC 161.0 (C=N imine), 145.3 (dm,
1JCF = 222.0 Hz, C-2,6 py), 141.9 (m, C-4 py), 132.8 (dm,
1JCF = 255.0 Hz, C-3,5 py), 10.3 (C–H cyclopropyl), 5.3
(CH2-cyclopropyl) ppm. 19F-NMR (282 MHz, DMSO-d6):
δF −92.9 (m, 2F, F-2,6 py), −156.2 (m, 2F, F-3,5 py) ppm.
In this paper, we describe a short series process involving
the reaction of nitrogen- and oxygen-centered difunctional
nucleophiles derived from amidoximes and pentafuoropyri-
dine for the synthesis of novel fuorinated products.
Experimental
N′‑((perfuoropyridin‑4‑yl)oxy)benzimidamide (4b)
All the solvents and starting materials were obtained com-
mercially (Merck). Solvents were dried using the literature-
recommended procedures and then were distilled before
use. 1H NMR spectra were recorded at 300 MHz. 13C NMR
spectra were recorded at 75 MHz. 19F NMR spectra were
recorded at 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).
Following representative procedure, preparative thin-
layer chromatography (EtOH/EtOAc, 1:1), Yield: 69%,
white oil, (Found: C, 50.1; H, 2.2; N, 13.9. C12H7F4N3O
requires: C, 50.5; H, 2.5; N, 14.7%). IR (KBr): νmax 3346
(NH), 1738 (C=N) cm−1. 1H-NMR (300 MHz, DMSO-d6):
δH 7.42–7.73 (5H, Ar–H), 5.11 (bs, 2H, NH2) ppm. 13C-
NMR (75 MHz, DMSO-d6): δC 156.6, 146.7, 145.2, 131.3,
130.1, 129.0, 126.4, 124.3 ppm. 19F-NMR (282 MHz,
DMSO-d6): δF −90.6 (m, 2F, F-2,6 py), −155.3 (m, 2F,
F-3,5 py) ppm.
General procedure for synthesis of amidoximes
under ultrasonic irradiation 2a–i
The mixture of nitrile 1 (1 mmol) and hydroxylamine
solution 50% (2 mmol) in ethanol (15 mL) was irradiated
with ultrasound for 20–50 min. The progress of the reac-
tion was monitored by TLC. After completion, the mixture
was diluted with water (10 mL) and extracted with diethyl
ether (2 × 10 mL). The combined organic layer was dried
over anhydrous MgSO4 and concentrated to aford the pure
amidoxime.
4‑bromo‑N′‑((perfuoropyridin‑4‑yl)oxy)benzimidamide
(4c)
Following representative procedure, preparative thin-layer
chromatography (EtOH/EtOAc, 1:1), Yield: 77%, white
oil, (Found: C, 38.8; H, 1.2; N, 10.8. C12H6BrF4N3O
requires: C, 39.6; H, 1.7; N, 11.5%). IR (KBr): νmax 3488,
1
3334 (NH2), 1640 (C=N) cm−1. H-NMR (300 MHz,
DMSO-d6): δH 7.69 (d, 2H, 3JHH = 8.5 Hz, Ar–H), 7.63 (d,
2H, 3JHH = 8.5 Hz, Ar–H), 7.20 (bs, 2H, NH2) ppm. 13C-
NMR (75 MHz, DMSO-d6): δC 156.7, 147.8, 145.0, 136.3,
131.6, 129.7, 124.3, 123.0 ppm. 19F-NMR (282 MHz,
DMSO-d6): δF −92.3 (m, 2F, F-2,6 py), −155.9 (m, 2F,
F-3,5 py) ppm.
General procedure for reactions
between pentafuoropyridine and amidoximes 4a–g
Potassium carbonate (3 mmol) was added to a solution
of amidoxime 2 (1 mmol) in acetonitrile (5 mL), and the
mixture was stirred at room temperature for 30 min. Then,
pentafuoropyridine 3 (1 mmol) was added, and the result-
ing solution was refuxed for 6 h. The reaction mixture
was poured into water (10 mL) and extracted with CHCl3
(3 × 10 mL) and dried over MgSO4 and the solvent evapo-
rated. The product was obtained after purifcation with pre-
parative thin-layer chromatography (EtOH/EtOAc).
N′‑((perfuoropyridin‑4‑yl)oxy)‑2‑phenylacetimidamide
(4d)
Following representative procedure, preparative thin-layer
chromatography (EtOH/EtOAc, 1:3), Yield: 80%, white oil,
1
IR (KBr): νmax 3396 (NH2), 1658 (C=N) cm−1. H-NMR
N′‑((perfuoropyridin‑4‑yl)oxy)
(300 MHz, DMSO-d6): δH 7.05–7.72 (5H, Ar–H), 6.93 (bs,
2H, NH2), 4.51 (s, CH2) ppm. 13C-NMR (75 MHz, DMSO-
d6): δC 151.3, 144.5, 143.0, 130.3, 130.1, 128.6, 125.5,
123.9, 34.2 ppm. 19F-NMR (282 MHz, DMSO-d6): δF −95.3
(m, 2F, F-2,6 py), −96.4 (m, 2F, F-2,6 py), −154.0 (m, 2F,
F-3,5 py), −154.4 (m, 2F, F-3,5 py) ppm.
cyclopropanecarboximidamide (4a)
Following representative procedure, preparative thin-layer
chromatography (EtOH/EtOAc, 1:1), Yield: 71%, white
oil, (Found: C, 42.9; H, 2.1; N, 16.5. C9H7F4N3O requires:
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J IRAN CHEM SOC
2‑(4‑methoxyphenyl)‑N′‑((perfuoropyridin‑4‑yl)oxy)
5,7,8‑trifuoro‑3‑(4‑methoxybenzyl)‑4H‑pyrido[3,4‑e]
acetimidamide (4e)
[1,2,4] oxadiazine (4h)
Following representative procedure, preparative thin-layer
chromatography (EtOH/EtOAc, 1:1), Yield: 67%, white oil,
Following representative procedure, preparative thin-
layer chromatography (EtOH/EtOAc, 1:3), Yield: 30%,
white oil, (Found: C, 54.0; H, 2.8; N, 13.2. C14H10F3N3O2
requires: C, 54.4; H, 3.3; N, 13.6%). IR (KBr): νmax 3416
1
IR (KBr): νmax 3395 (NH2), 1659 (C=N) cm−1. H-NMR
(300 MHz, DMSO-d6): δH 6.76–7.37 (Ar–H), 6.64 (bs,
2H, NH2), 4.43, 4.45, 4.57, 4.59 (s, CH2), 3.76, 3.78, 3.81,
3.82 (s, OCH3) ppm. 13C-NMR (75 MHz, DMSO-d6): δC
159.1, 156.5, 152.9, 129.3, 129.0, 125.8, 114.5, 114.0, 55.3,
36.7 ppm. 19F-NMR (282 MHz, DMSO-d6): δF −94.5 (m,
2F, F-2,6 py), −153.2 (m, 2F, F-3,5 py) ppm.
1
(NH), 1636 (C=N) cm−1. H-NMR (300 MHz, DMSO-
d6): δH 6.76–7.30 (5H, Ar–H and NH), 3.69 (s, 2H, CH2),
3.49 (s, 3H, OCH3) ppm. 13C-NMR (75 MHz, DMSO-
d6): δC 154.2, 153.6, 149.4, 145.2, 136.1, 134.6, 130.7,
127.1, 120.7, 116.4, 48.3, 40.7 ppm. 19F-NMR (282 MHz,
DMSO-d6): δF −73.5 (m, 1F, F-6 py), −102.7 (m, 1F, F-2
py), −172.0 (m, 1F, F-5 py) ppm.
N′‑((perfuoropyridin‑4‑yl)
oxy)‑3‑phenylpropanimidamide (4f)
Following representative procedure, preparative thin-layer
chromatography (EtOH/EtOAc, 1:1), Yield: 74%, white oil,
(Found: C, 53.2; H, 3.1; N, 12.9. C14H11F4N3O requires: C,
53.7; H, 3.5; N, 13.4%). IR (KBr): νmax 3500, 3404 (NH2),
5,7,8‑trifuoro‑3‑(pyridin‑2‑yl)‑4H‑pyrido[3,4‑e] [1,2,4]
oxadiazine (4i)
Following representative procedure, preparative thin-
layer chromatography (EtOH/EtOAc, 1:6), Yield: 83%,
white oil, (Found: C, 49.3; H, 1.5; N, 20.7. C11H5F3N4O
requires: C, 49.6; H, 1.9; N, 21.0%). IR (KBr): νmax 3388
(NH), 1648 (C=N) cm−1. 1H-NMR (300 MHz, DMSO-d6):
δH 8.67 (m, 1H, py-H), 7.84–7.95 (2H, py-H), 7.54 (m, 1H,
py-H), 6.95 (s, 1H, NH) ppm. 13C-NMR (75 MHz, DMSO-
d6): δC 151.3, 150.0, 146.4, 144.9, 136.1, 135.2, 131.7,
123.6, 120.4, 117.5 ppm 19F-NMR (282 MHz, DMSO-d6):
δF −92.17 (m, 1F, F-6 py), −152.8 (m, 1F, F-2 py), −160.8
(m, 1F, F-5 py) ppm.
1
1631 (C=N) cm−1. H-NMR (300 MHz, DMSO-d6): δH
7.00–7.67 (5H, Ar–H), 6.93 (bs, 2H, NH2), 4.21 (t, 2H,
3JHH = 6.1 Hz, CH2), 3.13 (t, 2H, 3JHH = 6.1 Hz, CH2) ppm.
13C-NMR (75 MHz, DMSO-d6): δC 150.1, 145.4, 142.6,
133.6, 132.2, 127.1, 125.7, 122.4, 38.6, 35.1 ppm. 19F-NMR
(282 MHz, DMSO-d6): δF −92.8 (m, 2F, F-2,6 py), −156.0
(m, 2F, F-3,5 py) ppm.
N′‑((perfuoropyridin‑4‑yl)oxy)nicotinimidamide (4g)
Following representative procedure, preparative thin-layer
chromatography (EtOH/EtOAc, 1:1), Yield: 62%, white
solid, mp 142–145 °C, IR (KBr): νmax 3480 (NH), 1667
(C=N) cm−1. 1H-NMR (300 MHz, DMSO-d6): δH 8.88 (d,
1H, 3JHH = 4.0 Hz, py-H), 8.72 (m, 1H, py-H), 8.08 (m, 1H,
py-H), 7.53 (m, 1H, py-H), 7.36 (bs, 2H, NH2) ppm. 13C-
NMR (75 MHz, DMSO-d6): δC 161.3, 152.5, 149.7, 146.6,
142.9, 133.2, 132.7, 126.3, 121.6 ppm 19F-NMR (282 MHz,
DMSO-d6): δF −92.3 (m, 2F, F-2,6 py), −155.9 (m, 2F,
F-3,5 py) ppm.
General procedure for synthesis of N‑(perfuoropyr
idin‑4‑yl)‑N‑((perfuoropyridin‑4‑yl)oxy) imidamide
systems 4j, 4k
Potassium carbonate (3 mmol) was added to a solution
of amidoxime 2 (1 mmol) in acetonitrile (5 mL), and
the mixture was stirred at room temperature for 30 min.
Then, pentafuoropyridine 3 (2 mmol) was added, and
General procedure for synthesis of pyridooxadiazine
systems 4i, 4h
Potassium carbonate (3 mmol) was added to a solution of
amidoxime 2 (1 mmol) in acetonitrile (20 mL), and the
mixture was stirred at room temperature for 30 min. Then,
pentafuoropyridine 3 (1 mmol) was added, and the result-
ing solution was refuxed for 24 h. The reaction mixture
was poured into 10 mL of water and extracted with CHCl3
(3 × 10 mL) and dried over MgSO4 and the solvent evapo-
rated. The product was obtained after purifcation with pre-
parative thin-layer chromatography (EtOH/EtOAc).
Scheme 1 Synthesis of precursor amidoximes under ultrasonic irra-
diation
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J IRAN CHEM SOC
Table 1 Reaction of amidoxime derivatives with pentafuoropyridine
Entry
Amidoxime (2)
Product (3)
%Yield
1
71
2
3
69
77
4
5
80
67
6
7
74
62
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J IRAN CHEM SOC
Table 1 (continued)
Entry
Amidoxime (2)
Product (3)
%Yield
8
9
65
75
10
11
70
35
Scheme 2 Synthesis of
pyridooxadiazine system from
pentafuoropyridine
the resulting solution was refuxed for 7 h. The reaction
mixture was poured into 10 mL of water and extracted
with CHCl3 (3 × 10 mL) and dried over MgSO4 and the
solvent evaporated. The product was obtained after purif-
cation with preparative thin-layer chromatography (EtOH/
EtOAc).
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Scheme 3 Synthesis of 4j and
4k
N‑(perfuoropyridin‑4‑yl)‑N‑((perfuoropyridin‑4‑yl)
synthesized these compounds from the reaction of carboni-
trile derivatives with hydroxylamine solution under ultra-
sonic irradiation in short reaction time and in high yields
(Scheme 1).
oxy)cyclohexanecarboximidamide (4j)
Following representative procedure, preparative thin-layer
chromatography (EtOH/EtOAc, 1:3), Yield: 21%, white oil,
(Found: C, 46.3; H, 2.7; N, 12.5. C17H12F8N4O requires: C,
46.4; H, 2.6; N, 12.7%). IR (KBr): νmax 3373 (NH), 1648
Amidoximes have three nucleophilic centers (two N
and one O), and it is clear that the oxygen atom in the
amidoxime is a better nucleophile than the nitrogen atoms
because of the alpha effect and less hinderers around the
oxygen atom. It is interesting to know which site is firstly
attacked in aromatic nucleophilic substitution reactions.
For this purpose, we studied reaction between pentafluor-
opyridine 1 and trifunctional amidoximes 2. The effect of
solvent was investigated using the reaction of pentafluo-
ropyridine 3 and N′-hydroxycyclopropanecarboximidam
ide 2a in the presence of potassium carbonate. At the ace-
tonitrile, the reaction gave an excellent yield, whereas the
yields were low or trace in other solvents (THF, DMF).
The final product was the same in all solvents. The reac-
tion of pentafluoropyridine with amidoxime 2a, in the
presence of potassium carbonate in the acetonitrile, gave
the desired N′ ((perfluoropyridin-4-yl)oxy)cyclopropane-
carboximidamide 4a (Table 1, entry 1), arising from the
substitution of the most activated fluorine atom at the
4-position of the pyridine ring, in excellent yield after
purification using preparative thin-layer chromatography
1
(C=N) cm−1. H-NMR (300 MHz, DMSO-d6): δH 6.15
(s, 1H, NH), 1.07–1.66 (11H, cyclohexyl) ppm. 13C-NMR
(75 MHz, DMSO-d6): δC 153.4, 149.6, 144.3, 143.6, 140.7,
134.1, 130.9, 29.6, 23.6, 23.5, 13.2 19F-NMR (282 MHz,
DMSO-d6): δF −93.0 (m, 2F, F-2,6 py), –96.3 (m, 2F, F-2,6
py), −155.9 (m, 2F, F-3,5 py), −156.1 (m, 2F, F-3,5 py)
ppm.
4‑bromo‑N‑(perfuoropyridin‑4‑yl)‑N‑((perfuoropyridi
n‑4‑yl)oxy)benzimidamide (4k)
Following representative procedure, preparative thin-layer
chromatography (EtOH/EtOAc, 1:3), Yield: 21%, white oil,
(Found: C, 39.5; H, 0.8; N, 10.3. C17H5BrF8N4O requires:
C, 39.8; H, 1.0; N, 10.9%). IR (KBr): νmax 3420 (NH), 1573
1
(C=N) cm−1. H-NMR (300 MHz, DMSO-d6): δH 7.43
(d, 2H, 3JHH = 7.1 Hz, Ar–H), 7.35 (d, 2H, 3JHH = 7.1 Hz,
Ar–H), 6.25 (s, 1H, NH), 13C-NMR (75 MHz, DMSO-d6):
δC 158.5, 154.5, 144.8, 142.7, 133.0, 131.2, 130.8, 129.4,
126.1, 122.9 ppm 19F-NMR (282 MHz, DMSO-d6): δF
−88.5 (m, 2F, F-2,6 py), −90.6 (m, 2F, F-2,6 py), −148.0
(m, 2F, F-3,5 py), −156.7 (m, 2F, F-3,5 py) ppm.
1
eluted by ethanol/ethyl acetate. HNMR and 19FNMR
analysis confirmed product 4a. This observation showed
that nucleophile derived from N′-hydroxycyclopropaneca
rboximidamide 2a reacted with pentafluoropyridine from
the oxygen site. In 19FNMR spectrum of 4a, two reso-
nances (−92.9 and −156.2 ppm) indicate the displace-
ment of fluorine atom attached to the 4-position of the
pyridine ring. Fluorine atoms located at ortho and meta
positions to ring nitrogen showed chemical shifts at −92.9
and −156.2 ppm, respectively. This observation, with
Results and discussion
Amidoximes can be prepared from the reaction of car-
bonitriles with hydroxylamine [26]. In this paper, we have
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J IRAN CHEM SOC
the other IR and NMR data, indicated that amidoxime
2a reacted with pentafluoropyridine from oxygen site to
form product 4a based on hard–hard interaction princi-
ple. With this encouraging result in hand, we performed
the reaction of various amidoximes with pentafluoropyri-
dine. Similar to 2a, the reaction of amidoximes 2b–g with
pentafluoropyridine 3 gave corresponding products 4b–g
(Table 1, entry 2–7).
Conclusion
We showed that pentafuoropyridine can successfully react
with amidoximes from oxygen site. [6,6] pyridooxadiazine
scafolds can be readily synthesized in one-pot process
from pentafuoropyridine and amidoximes after prolonged
heating. Also reaction of amidoximes with pentafuoro-
pyridine in 1:2 mol ratio gave bis-perfuoropyridyl bridged
compounds.
Given the successful synthesis of 4, we studied the
cyclization reactions involving 2 and 3 in some cases in
the presence of potassium carbonate and in dilute acetoni-
trile solution to minimize intermolecular reaction. Both
2e and 2 h gave annelated products 4h and 4i in one-pot
processes in good yield, albeit after prolonged heating
(24 h), following purification using plate chromatogra-
phy eluted by ethanol/ethyl acetate of the crude products
(Scheme 3). The progress of these cyclization reactions
was monitored by 19F-NMR, and the disappearance of
resonances attributed to fluorine atoms located at the 4-
and 3-positions of pentafluoropyridine allowed simple
identification of cyclized products 4h and 4i. It is the
result of substitution at the 4-position of the pyridine ring
by the oxygen of amidoxime followed by intramolecular
ring closure at the geometrically accessible 3-position
of the pyridine ring by the primary nitrogen of amidox-
ime. In 4h, fluorines located at 6-, 2- and 5-positions
of pyridine ring had chemical shifts −73.5, −102.7 and
Acknowledgements The authors wish to thank Vali-e-Asr University
of Rafsanjan for partially funding this work.
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1
−172.0 ppm, respectively. The H- and 13C-NMR spec-
trum of 4h revealed signals as expected. Similarly, in 4i,
fluorines located at 6-, 2- and 5-positions of a pyridine
ring had chemical shifts −92.2, −152.8 and −160.8 ppm,
respectively (Scheme 2).
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Reaction of amidoxime 2i with pentafuoropyridine 3
in 1:2 mol ratio, in the presence of potassium carbonate,
and also in concentrated acetonitrile solution to maximize
intermolecular reaction at refux gave a single product,
N-(perfluoropyridin-4-yl)-N-((perfluoropyridin-4-yl)
oxy)cyclohexanecarboximidamide 4j, in good yield.
Four resonances by 19F NMR (−93.0, −96.3, −155.9
and −156.1 ppm) indicate the displacement of fuorine
atoms attached to 4-position of the two pyridine rings
(Scheme 3). Purifcation of 4j was achieved by column
chromatography. Identification of 4j was done by 19F
NMR analysis, in which the resonance attributed to fuo-
rines located ortho to ring nitrogen has a chemical shift
of −93.0 and −96.3 ppm similar to the shift observed in
analogue systems. The corresponding resonance for fuo-
rines located meta to ring nitrogen in 4j occurs at −155.9
and −156.1 ppm similar to the analogous system. In a
similar condition, reaction of amidoxime 2c with pen-
tafluoropyridine gave 4-bromo-N-(perfluoropyridin-4-
yl)-N-((perfluoropyridin-4-yl)oxy)benzimidamide 4 k
(Scheme 3).
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