Dipyrido[1,2-b:3′,4′-e][1,2,4]triazine Scaffolds from Pentafluoropyridine

Article abstract of DOI:10.1002/jhet.3283

Annelation reaction between pentafluoropyridine and diaminodihydro substituted pyridine derivatives gave dipyrido[1,2-b:3′,4′-e][1,2,4]triazine systems as major products arising from the initial nucleophilic substitution of more nucleophilic N-amino group

Full text of DOI:10.1002/jhet.3283

Month 2018
Dipyrido[1,2-b:30,40-e][1,2,4]triazine Scaffolds from Pentafluoropyridine
*
Fahimeh Bahadornia, and Alireza Poorfreidoni
Reza Ranjbar-Karimi,
Ali Darehkordi,
Department of Chemistry, Faculty of Science, Vali-e-Asr University, Rafsanjan 77176, Islamic Republic of Iran
*E-mail: alireza_poorfreidoni@yahoo.com
Received April 18, 2018
DOI 10.1002/jhet.3283
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
Annelation reaction between pentafluoropyridine and diaminodihydro substituted pyridine derivatives
gave dipyrido[1,2-b:30,40-e][1,2,4]triazine systems as major products arising from the initial nucleophilic
substitution of more nucleophilic N-amino group of pyridone ring at 4-position of the pyridine ring followed
by intramolecular cyclization at 3-position of pyridine ring. Also, 6-amino-2-oxo-1-((perfluoropyridin-4-yl)
amino)-4-aryl-1,2-dihydropyridine-3,5-dicarbonitrile derivatives were obtained as side products. The struc-
tures of all the compounds were confirmed by IR, 1H NMR, 13C NMR, and 19F NMR spectroscopy as well
as elemental analysis.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
difunctional nitrogen and oxygen nucleophiles attached to
aromatic rings [22].
Fluor-containing heterocyclic systems are attractive
synthetic scaffolds and have a wide range of applications
in biochemistry, organic chemistry, and pharmaceutical
chemistry [1–4]. Pentafluoropyridine is an important
perfluorinated heterocycle that highly regarded in organic
chemistry as an excellent scaffold for the synthesis of
other heterocyclic and macrocyclic compounds [5–7].
The chemistry of pentafluoropyridine is dominated by
nucleophilic substitution reactions due to the presence of
five fluorine atoms attached to the pyridine ring [8,9].
Nucleophilic substitution reactions of pentafluoropyridine
have been reported with various S, N, O, P, and C
nucleophiles [10–14]. Regiochemistry of these reactions
basically affected by the nature of the solvent,
nucleophile, and reaction conditions.
Perfluorinated pyridines are useful building blocks for the
synthesis of fluorinated ring-fused heterocycles on reaction
with various equal and unequal bidentate nucleophiles
[5,15–18]. In the last few years, we have been pursuing
synthesis of ring-fused systems on the reaction of
bidentate nucleophiles with perfluoropyridines [19–21].
We have shown difluorinated tetrahydropyrido[3,4-b][1,4]
oxazine, thiazine, and pyrazine scaffolds, as well as
imidazopyridine systems, can be readily synthesized by
reaction of 2,3,5,6-tetrafluoro-4-(phenylsulfonyl) pyridine
with a variety of bidentate nucleophiles [20,21]. In another
study, we have been synthesized [6,6,6] ring fused
tricyclic systems on the reaction of pentafluoropyridine
or 2,3,5,6-tetrafluoro-4-(phenylsulfonyl)pyridine with
The 1,2,4-triazine systems are an important class of
heterocyclic compounds, and it is well known for
their biological activities such as anticancer [23], anti-
convulsant [24], antimalarial [25], antitumor [26], and
antiviral [27]. The most available method for the synthesis
of these compounds is mainly based on the reactions
of amidrazones with 1,2-diketone compounds [28,29].
Also, the multicomponent reactions of dicarbonyl
compounds, hydrazides, and ammonium acetate is a
pathway to the synthesis of 3,5-disubstituted 1,2,4-trizaine
compounds [30].
Continuing our research on synthesis fluorinated
ring-fused heterocycles, we herein report the synthesis of
dipyrido[1,2-b:30,40-e][1,2,4]triazine scaffolds from the
reaction of pentafluoropyridine with diamino-dihydro
substituted pyridine derivatives.
RESULTS AND DISCUSSION
Diamino-dihydro substituted pyridine derivatives were
synthesized from the reaction of corresponding
benzilidenmalonolnitriles 3 with 2-cyanoacetohydrazide 4
according to the literature procedure (Scheme 1) [31].
The reaction of diaminodihydro substituted pyridine
derivatives 5a–j with pentafluoropyridine 6 was carried
out in CH3CN in the presence of potassium carbonate
at 85°C. Reaction of 1,6-diamino-2-oxo-4-phenyl-1,2-
dihydropyridine-3,5-dicarbonitrile 5a with pentafluoropyridine
© 2018 Wiley Periodicals, Inc.

R. Ranjbar-Karimi, A. Darehkordi, F. Bahadornia, and A. Poorfreidoni
Vol 000
Scheme 1. Synthesis of diamino-dihydro substituted pyridines.
6
gave 1,3,4-trifluoro-7-oxo-9-phenyl-7,11-dihydro-5H-
showed a broad singlet peak at δ = 9.23 ppm for two
NH groups. It also indicated two multiple peaks in the
range of δ = 7.19–7.31 and 7.51–7.62 ppm for aromatic
hydrogens. In 13C NMR spectrum of compound 7a,
carbonyl group was located at δ = 161.9 ppm and other
pyridone carbons were located at δ = 74.6, 86.3, 157.9,
and 158.0 ppm. Aromatic carbons of benzene and pyridine
rings were located in the range of δ = 128.0–135.6 ppm.
Two peaks appeared at δ = 114.9 and 115.6 ppm related
to cyano groups. IR spectrum 7a showed absorption
bands at 3207 and 3299 cmꢀ1 for NH stretching and
absorption bands at 2220 and 1692 cmꢀ1 for CN and C═O
stretching, respectively. In 19F NMR analysis of 8a, the
resonances of meta and ortho fluorines to ring nitrogen
were located at δ = ꢀ156.2 and 97.4 ppm, respectively.
These two resonances indicate the displacement of
fluorine atom attached to the 4-position of the pyridine
ring with 2-pyridone 5a and cyclic product not formed.
1H NMR spectrum of compound 8a showed two broad
singlet peaks at δ = 5.80 and 10.34 ppm for NH and NH2
groups, respectively. It also indicated two multiple
peaks in the range of δ = 7.29–7.44 and 7.45–7.50 for
aromatic hydrogens. In 13C NMR spectrum of compound
8a, peaks were located at δ = 160.2 ppm and δ = 83.5,
157.3, and 158.1 ppm attributed to carbonyl group and
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile 7a as
major product and 6-amino-2-oxo-1-((perfluoropyridin-4-yl)
amino)-4-phenyl-1,2-dihydropyridine-3,5-dicarbonitrile 8a as
side product (Table 1, Code a) after purification using plate
chromatography eluted by ethyl acetate/MeOH. Product 7a
was obtained by substitution of the amino group attached to
ring nitrogen 5a at the 4-position of the pyridine ring, followed
by intramolecular ring closure at the geometrically accessible
3-position of the pyridine ring by another amino group
5a. Product 8a was formed by nucleophilic attack of the
N-amino group of the compound 5a to the 4-position of
pentafluoropyridine. The chemoselectivity of nucleophilic
substitution on pentafluoropyridine 6 reflected by the higher
nucleophilicity of the N-amino group over the amino group.
The structures of 7a and 8a were confirmed by 19F,
1H, and 13C NMR analysis. Three resonances by 19F
NMR (ꢀ93.8, ꢀ157.0, and ꢀ165.7 ppm) indicate the
displacement of fluorine atoms attached to the 3-position
and 4-position of the pyridine ring with 2-pyridone 5a as a
bidentate nucleophile. In 19F NMR analysis of 7a, the
resonances of two ortho fluorines (F-6 and F-2) to ring
nitrogen were located at δ = ꢀ157.0 and ꢀ165.7 ppm and
meta fluorine (F-5) to ring nitrogen was located at
δ = ꢀ93.8 ppm. 1H NMR spectrum of compound 7a
Table 1
Reaction of diamino-dihydro substituted pyridines with pentafluoropyridine.
Code
Ar
7, Yield (%)
8, Yield (%)
a
b
c
d
e
f
g
h
i
C6H5
4-Me-C6H4
4-OMe-C6H4
2,4-di (OMe)-C6H3
4-Cl-C6H4
38
40
40
52
48
46
45
51
33
38
21
trace
trace
trace
trace
trace
trace
trace
trace
trace
2-Br-C6H4
2-NO2-C6H4
3-NO2-C6H4
4-NO2-C6H4
4-F-C6H4
j
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Dipyrido[1,2-b:30,40-e][1,2,4]triazine Systems Synthesized from Reaction between
Pentafluoropyridine and Diamino-dihydro Substituted Pyridine Derivatives
other carbons of pyridone ring, respectively. Also, a peak
appeared at δ = 117.2 related to CN group. In IR spectrum
8a showed an absorption band at 3416 cmꢀ1 for NH
stretching and absorption bands at 2215 and 1652 cmꢀ1
for CN and C═O stretching, respectively.
Thin-layer chromatography analysis was performed on
silica gel thin-layer chromatography plates (Merck).
Column chromatography was carried out on silica gel
with mixed solvents (n-hexane/ethyl acetate).
General procedure for reaction between pentafluoropyridine
Similarly, the reaction of 2-pyridones 5b–j with
pentafluoropyridine gave ring-fused compounds 7b–j as
major product and uncyclized products 8b–j (Table 1,
Code b–j). In 19F NMR spectra of compounds 7b–j,
F-5 of pyridine ring was located in the range of
δ = (ꢀ96.3.3)–(ꢀ92.9) ppm, F-6 was located in the
range of δ = (ꢀ158.8)–(ꢀ141.3) ppm, and F-2 was
located in the range of δ = (ꢀ167.5)–(ꢀ163.6) ppm.
1H NMR spectra showed aromatic hydrogens in the
range of δ = 7.93–9.92 ppm for NH and some signals
in the range of δ = 6.60–8.40 ppm for aromatic
hydrogens. In 13C NMR spectra, carbonyl group carbon
was located in the range of δ = 159.0–165.0 ppm,
cyano groups carbon was located in the range of
δ = 113.2–117.6 ppm, pyridone carbons were located
in the ranges of δ = 73.7–87.1 ppm and 156.0–
161.7 ppm, and aromatic carbons were located in the
range of δ = 113.7–159.2 ppm. Compounds 8b–j
were obtained in trace (Table 1, Code b–j).
The structure of compounds 8b–j confirmed by 19F
NMR. In 19F NMR spectra of these compounds,
ortho fluorine atoms were located in the range of
δ = (ꢀ96.1)–(ꢀ98.3) ppm and meta fluorine atoms in
the range of δ = (ꢀ147.3)–(ꢀ156.8) ppm.
and diamino dihydropyridine derivatives.
Potassium
carbonate (3 mmol) was added to a solution of diamino-
dihydro substituted pyridine derivative 5 (1 mmol) in
CH3CN (8 mL) and the mixture was stirred at room
temperature for 30 min. Then, pentafluoropyridine 6
(1 mmol) was added, and the resulting solution was
refluxed for appropriate time. The reaction mixture was
poured onto 10-mL water, extracted with chloroform
(3 × 8 mL), and then dried with MgSO4 and solvent
evaporated. Purification was performed using column
chromatography (EtOAc/MeOH).
1,3,4-Trifluoro-7-oxo-9-phenyl-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile (7a).
Potassium carbonate (0.414 g, 3 mmol), 1,6-diamino-2-
oxo-4-phenyl-1,2-dihydropyridine-3,5-dicarbonitrile
(0.251 g, 1 mmol), pentafluoropyridine 6 (0.169 g,
1 mmol), and CH3CN (8 mL), after refluxing for 48 h and
using column chromatography (EtOAc/MeOH, 15:1),
5a
gave
1,3,4-trifluoro-7-oxo-9-phenyl-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile
7a (major product): 38%; yellow solid; mp: 170–173°C.
(Found: C, 56.64; H, 1.59; N, 21.90; C18H7F3N6O
requires: C, 56.85; H, 1.86; N, 22.10). IR (KBr): ν 3207
(N-H), 3299 (N-H), 2220 (CN), 1692 (C═O) cmꢀ1. H
1
NMR (300 MHz, DMSO-d6): δH 9.23 (bs, 2H, NH),
7.51–7.62 (m, 3H, Ar-H), 7.19–7.31 (m, 2H, Ar-H)
ppm. 13C NMR (75 MHz DMSO-d6): δC 161.9 (C═O),
158.0 (pyridone-C), 157.9 (pyridone-C), 135.6 (dm,
1JCF = 265.4 Hz, C-6 py), 134.2 (Ar-C), 130.7 (Ar-CH),
128.7 (Ar-CH), 128.0 (Ar-CH), 127.9 (dm,
1JCF = 229.8 Hz, C-5 py), 115.6 (CN), 114.9 (CN), 86.3
(pyridone-C), 74.6 (pyridone-C) ppm. 19F NMR
(282 MHz, DMSO-d6): δF ꢀ93.8 (m, 1F, F-5 py),
ꢀ157.0 (m, 1F, F-6 py), ꢀ165.7 (m, 1F, F-2 py) ppm;
and 6-amino-2-oxo-1-((perfluoropyridin-4-yl)amino)-4-
phenyl-1,2-dihydropyridine-3,5-dicarbonitrile 8a; 21%;
brown solid; mp: 150–153°C. IR (KBr): ν 3416 (N-H),
CONCLUSION
In conclusion, we demonstrated the efficient synthesis of
some dipyrido[1,2-b:30,40-e][1,2,4]triazine systems from
the reaction of pentafluoropyridine with diaminodihydro
substituted pyridine derivatives. Also, 6-amino-2-oxo-
1-((perfluoropyridin-4-yl)amino)-4-aryl-1,2-dihydropyri-
dine-3,5-dicarbonitriles formed as side product.
The chemoselectivity of nucleophilic substitution on
pentafluoropyridine could be concluded based on the
higher nucleophilicity of the N-amino group due to α-effect.
2215 (CN), 1652 (C═O) cmꢀ1 1H NMR (300 MHz,
.
DMSO-d6): δH 10.34 (1H, NH), 7.45–7.50 (m, 3H, Ar-H),
7.29–7.44 (m, 2H, Ar-H), 5.80 (2H, NH2) ppm. 13C NMR
(75 MHz, DMSO-d6): δC 160.2 (C═O), 158.1 (pyridone-
C), 157.3 (pyridone-C), 135.5 (Ar-C), 128.5 (Ar-CH),
128.2 (Ar-CH), 128.0 (Ar-CH), 117.2 (CN), 83.5
(pyridone-C) ppm. 19F NMR (282 MHz, DMSO-d6): δF
EXPERIMENTAL
All the solvents and starting materials were obtained
1
commercially (Merck). H NMR spectra were recorded at
300 MHz, 13C NMR spectra at 75 MHz, and 19F NMR
spectra at 282 MHz. IR spectra were recorded on a
Thermo Scientific-Nicolet iS10 spectrometer in a KBr
matrix. All melting points were obtained by Stuart
Scientific apparatus. The elemental analyses for C, H, and
N were performed using Heraeus CHN–O rapid analyzer.
ꢀ97.4 (m, 2F, F-2,6 py), ꢀ156.2 (m, 2F, F-3,5 py) ppm.
1,3,4-Trifluoro-7-oxo-9-(p-tolyl)-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile (7b).
Potassium carbonate (0.414 g, 3 mmol), 1,6-diamino-2-
oxo-4-(p-tolyl)-1,2-dihydropyridine-3,5-dicarbonitrile 5b
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Ranjbar-Karimi, A. Darehkordi, F. Bahadornia, and A. Poorfreidoni
Vol 000
(0.265 g, 1 mmol), pentafluoropyridine 6 (0.169 g,
1 mmol), and CH3CN (8 mL), after refluxing for 42 h
and using column chromatography (EtOAc/MeOH, 15:2),
9-(2,4-Dimethoxyphenyl)-1,3,4-trifluoro-7-oxo-7,11-dihydro-
5H-dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile
(7d). Potassium carbonate (0.414 g, 3mmol), 1,6-diamino-
4-(2,4-dimethoxyphenyl)-2-oxo-1,2-dihydropyridine-3,5-
dicarbonitrile 5d (0.311 g, 1 mmol), pentafluoropyridine
6 (0.169 g, 1 mmol), and CH3CN (8 mL), after refluxing
for 40 h and using column chromatography (EtOAc/MeOH,
3:1), gave 9-(2,4-dimethoxyphenyl)-1,3,4-trifluoro-7-oxo-
7,11-dihydro-5H-dipyrido[1,2-b:30,40-e][1,2,4]triazine-
gave
1,3,4-trifluoro-7-oxo-9-(p-tolyl)-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile
7b, 40%; yellow solid; mp: 176–179°C. (Found: C,
57.59; H, 2.21; N, 21.08; C19H9F3N6O requires: C,
57.87; H, 2.30; N, 21.31). IR (KBr): ν 3207 (N-H),
3306 (N-H), 2221 (CN), 1624 (C═O) cmꢀ1. H NMR
1
8,10-dicarbonitrile
7d,
52%;
yellow
solid;
(300 MHz, DMSO-d6): δH 9.04 (2H, NH), 7.46 (d, 2H,
3
3JHH = 8.1 Hz, Ar-H), 7.37 (d, 2H, JHH = 8.1 Hz,
mp:190–193°C. (Found: C, 54.28; H, 2.41; N, 18.86;
C20H11F3N6O3 requires: C, 54.55; H, 2.52; N, 19.09).
Ar-H), 2.39 (s, 3H, CH3) ppm. 13C NMR (75 MHz
DMSO-d6): δC 161.6 (C═O), 158.1 (pyridone-C),
IR (KBr): ν 3447 (N-H), 2216 (CN), 1644 (C═O) cmꢀ1
.
1H NMR (300 MHz, DMSO-d6): δH 9.92, 7.94 (NH),
1
157.8 (pyridone-C), 143.2 (dm, JCF = 235.2 Hz, C-6
3
7.13 (d, 1H, JHH = 8.4 Hz, Ar-H), 6.67 (s, 1H, Ar-H),
py), 140.6 (Ar-C), 137.9 (m, C-2 py), 131.4 (Ar-C),
3
1
6.60 (d, 1H, JHH = 9 Hz, Ar-H), 3.82 (s, 3H, OCH3),
131.3 (dm, JCF = 254.9 Hz, C-5 py), 129.3 (Ar-CH),
3.78 (s, 3H, OCH3) ppm. 13C NMR (75 MHz
DMSO-d6): δC 164.1 (C═O), 160.6 (pyridone-C),
156.1 (pyridone-C), 154.6 (Ar-C), 144.2 (dm,
1JCF = 223.0 Hz, C-6 py), 139.6 (m, C-2 py), 133.6
128.1 (Ar-CH), 115.9 (CN), 115.2 (CN), 86.3
(pyridone-C), 74.5 (pyridone-C), 21.0 (CH3) ppm.
19F NMR (282 MHz, DMSO-d6): δF ꢀ94.5 (m, 1F,
F-5), ꢀ157.7 (m, 1F, F-6), ꢀ166.6 (m, 1F, F-2 py)
ppm; and trace 6-amino-2-oxo-1-((perfluoropyridin-4-
yl)amino)-4-(p-tolyl)-1,2-dihydropyridine-3,5-dicarbonitrile
8b; brown solid; mp: 295°C. IR (KBr): ν 3448 (N-H), 2214
1
(dm, JCF = 258.3 Hz, C-5 py), 129.3 (Ar-CH), 127.5
(Ar-C), 117.6 (CN), 116.0 (CN), 113.7 (Ar-CH), 85.2
(pyridone-C), 73.7 (pyridone-C), 54.0 (OCH3), 52.3
(OCH3) ppm. 19F NMR (282 MHz, DMSO-d6): δF
ꢀ93.2 (m, 1F, F-5 py), ꢀ141.7 (m, 2F, F-6 py), ꢀ164.0
(m, 1F, F-2 py) ppm; and trace 6-amino-4-(2,4-
dimethoxyphenyl)-2-oxo-1-((perfluoropyridin-4-yl)
(CN), 1643 (C═O) cm .
ꢀ1 19F NMR (282 MHz, DMSO-d6):
δF ꢀ97.3 (m, 2F, F-2,6 py), ꢀ156.1 (m, 1F, F-3,5 py) ppm.
1,3,4-Trifluoro-9-(4-methoxyphenyl)-7-oxo-7,11-dihydro-
5H-dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile
(7c).
Potassium carbonate (0.414 g, 3 mmol), 1,6-
amino)-1,2-dihydropyridine-3,5-dicarbonitrile 8d, brown
solid; mp:218–220°C. IR (KBr): ν 3440 (N-H), 2213 (CN),
diamino-4-(4-methoxyphenyl)-2-oxo-1,2-dihydropyridine-
3,5-dicarbonitrile 5c (0.281 g, 1 mmol), pentafluoropyridine
6 (0.169 g, 1 mmol), and CH3CN (8 mL), after refluxing
for 42 h and using column chromatography (EtOAc/
MeOH, 15:2), gave 1,3,4-trifluoro-9-(4-methoxyphenyl)-
7-oxo-7,11-dihydro-5H-dipyrido[1,2-b:30,40-e][1,2,4]triazine-
8,10-dicarbonitrile 7c, 40%; yellow solid; mp: 220–222°C.
(Found: C, 55.50; H, 2.02; N, 20.32; C19H9F3N6O2 requires:
C, 55.62; H, 2.21; N, 20.48). IR (KBr): ν 3204 (N-H), 2216
(CN), 1606 (C═O) cmꢀ1. 1H NMR (300 MHz, DMSO-d6):
1643 (C═O) cmꢀ1 19F NMR (282 MHz, DMSO-d6): δF
.
ꢀ96.1 (m, 2F, F-2,6 py), ꢀ155.6 (m, 2F, F-3,5 py) ppm.
9-(4-Chlorophenyl)-1,3,4-trifluoro-7-oxo-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile (7e).
Potassium carbonate (0.414 g, 3 mmol), 1,6-diamino-4-(4-
chlorophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile
5e (0.258 g, 1 mmol), pentafluoropyridine 6 (0.169 g,
1 mmol), and CH3CN (8 mL), after refluxing for 40 h and
using column chromatography (EtOAc/MeOH, 5:1), gave
9-(4-chlorophenyl)-1,3,4-trifluoro-7-oxo-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile
7e, 48%; yellow solid; mp: 168–170°C. (Found: C,
51.95; H, 1.25; N, 20.00; C18H6ClF3N6O requires: C,
52.13; H, 1.46; N, 20.26). IR (KBr): ν 3447 (N-H),
3
δH 8.99 (2H, NH), 7.55 (d, 2H, JHH = 8.7 Hz, Ar-H),
3
7.12 (d, 2H, JHH = 8.8 Hz, Ar-H), 3.84 (s, 3H, OCH3)
ppm. 13C NMR (75 MHz, DMSO-d6): δC 161.2 (C═O),
161.2 (pyridone-C), 158.2 (pyridone-C), 157.8 (Ar-C), 143.3
(dm, JCF = 229.4 Hz, C-6 py), 138.0 (m, C-2 py), 131.3
(dm, JCF
1
2216 (CN), 1651 (C═O) cmꢀ1 1H NMR (300 MHz,
.
1
= 264.1 Hz, C-5 py), 130.1 (Ar-CH),
DMSO-d6): δH 9.73, 7.93 (NH), 7.58 (d, 2H,
3JHH = 8.6 Hz, Ar-H), 7.46 (3JHH = 8.5 Hz, Ar-H) ppm.
13C NMR (75 MHz, DMSO-d6): δC 162.3 (C═O), 159.0
(pyridone-C), 156.6 (pyridone-C), 134.7 (Ar-C), 133.9
(Ar-C), 129.9 (Ar-CH), 128.7 (Ar-CH), 116.9 (CN),
116.5 (CN), 86.9 (pyridone-C), 82.6 (pyridone-C) ppm.
19F NMR (282 MHz, DMSO-d6): δF ꢀ92.9 (m, 1F, F-5
py), ꢀ141.3 (m, 1F, F-6 py), ꢀ163.6 (m, 1F, F-2 py)
ppm; and trace 6-amino-4-(4-chlorophenyl)-2-oxo-1-
((perfluoropyridin-4-yl)amino)-1,2-dihydropyridine-3,5-
126.2 (Ar-C), 116.1 (CN), 115.4 (CN), 114.1 (Ar-CH), 86.2
(pyridone-C), 74.5 (pyridone-C), 55.4 (OCH3) ppm.
19F NMR (282 MHz, DMSO-d6): δF ꢀ94.6 (m, 1F, F-5 py),
ꢀ157.6 (m, 1F, F-6 py), ꢀ166.6 (m, 1F, F-2 py)
ppm; and trace 6-amino-4-(4-methoxyphenyl)-2-oxo-1-
((perfluoropyridin-4-yl)amino)-1,2-dihydropyridine-3,5-
dicarbonitrile 8c, brown solid; mp:220–223°C. IR (KBr):
ν 3447 (N-H), 2214 (CN), 1607 (C═O) cmꢀ1 19F NMR
.
(282 MHz, DMSO-d6): δF ꢀ97.3 (m, 2F, F-2,6 py),
ꢀ156.0 (m, 2F, F-3,5 py) ppm.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Dipyrido[1,2-b:30,40-e][1,2,4]triazine Systems Synthesized from Reaction between
Pentafluoropyridine and Diamino-dihydro Substituted Pyridine Derivatives
dicarbonitrile 8e, brown solid; mp: 210–213°C. IR (KBr):
ν 3449 (N-H), 2221 (CN), 1648 (C═O) cmꢀ1 19F NMR
129.4 (Ar-CH), 125.5 (Ar-CH), 115.1 (CN), 114.4 (CN),
86.2 (pyridone-C), 74.5 (pyridone-C) ppm. 19F NMR
(282 MHz, DMSO-d6): δF ꢀ94.5 (m, 1F, F-5 py), ꢀ157.4
(m, 1F, F-6 py), ꢀ166.6 (m, 1F, F-2 py) ppm; and trace 6-
amino-4-(2-nitrophenyl)-2-oxo-1-((perfluoropyridin-4-yl)
amino)-1,2-dihydropyridine-3,5-dicarbonitrile 8g, brown
solid; mp: 185°C. IR (KBr): ν 3447 (N-H), 2216 (CN),
.
(282 MHz, DMSO-d6): δF ꢀ96.6 (m, 2F, F-2,6 py),
ꢀ156.2 (m, 2F, F-3,5 py) ppm.
9-(2-Bromophenyl)-1,3,4-trifluoro-7-oxo-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile (7f).
Potassium carbonate (0.414 g, 3 mmol), 1,6-diamino-
4-(2-bromophenyl)-2-oxo-1,2-dihydropyridine-3,5-
1640 (C═O) cmꢀ1 19F NMR (282 MHz, DMSO-d6): δF
.
dicarbonitrile 5f (0.328 g, 1 mmol), pentafluoropyridine 6
(0.169 g, 1 mmol), and CH3CN (8 mL), after refluxing for
45 h and using column chromatography (EtOAc/MeOH,
5:1), gave 9-(2-bromophenyl)-1,3,4-trifluoro-7-oxo-7,11-
dihydro-5H-dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-
dicarbonitrile 7f, 46%; yellow solid; mp: 214°C. (Found: C,
46.88; H, 1.05; N, 18.05; C18H6BrF3N6O requires: C,
47.08; H, 1.32; N, 18.30). IR (KBr): 3208 (NH), 3305 (N-
ꢀ97.0 (m, 2F, F-2,6 py), ꢀ155.8 (m, 1F, F-3,5 py) ppm.
1,3,4-Trifluoro-9-(3-nitrophenyl)-7-oxo-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile (7h).
Potassium carbonate (0.414 g, 3 mmol), 1,6-diamino-4-(3-
nitrophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile
5g (0.296 g, 1 mmol), pentafluoropyridine 6 (0.169 g,
1 mmol), and CH3CN (8 mL), after refluxing for 40 h
and using column chromatography (EtOAc/MeOH, 10:1),
gave 1,3,4-trifluoro-9-(3-nitrophenyl)-7-oxo-7,11-dihydro-
5H-dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-
1
H), 2223 (CN), 1625 (C═O) cmꢀ1. H NMR (300 MHz,
3
DMSO-d6): δH 9.1 (NH), 7.83 (d, 1H, JHH = 7.9 Hz, Ar-
3
dicarbonitrile 7h, 51%; yellow solid; mp: 175–178°C.
(Found: C, 50.72; H, 1.17; N, 22.82; C18H6F3N7O3
requires: C, 50.84; H, 1.42; N, 23.05). IR (KBr): ν 3208
H), 7.53–7.60 (m, 2H, Ar-H), 7.48 (t, 1H, JHH = 6.6 Hz,
Ar-H) ppm. 13C NMR (75 MHz, DMSO-d6): δC 160.5
(C═O), 157.9 (pyridone-C), 157.4 (pyridone-C), 143.3
1
(NH), 3306 (N-H), 2220 (CN), 1650 (C═O) cmꢀ1. H
1
(dm, JCF = 231.4 Hz, C-6 py), 138.5 (m, C-2 py), 138.5
NMR (300 MHz, DMSO-d6): δH 8.21(NH), 8.35 (d, 1H,
(m, C-2 py), 135.6 (Ar-C), 133.0 (Ar-CH), 131.9 (Ar-C),
130.4 (dm, JCF = 255.0 Hz, C-5 py), 129.4 (Ar-CH),
3JHH = 8.2 Hz, Ar-H), 8.15 (s, 1H, Ar-H), 7.81 (t, 1H,
1
3
3JHH = 6.8 Hz, Ar-H), 7.75 (d, 1H, JHH = 7.4 Hz, Ar-H)
128.4 (Ar-CH), 120.2 (Ar-CH), 115.1 (CN), 114.3 (CN),
87.1 (pyridone-C), 75.2 (pyridone-C) ppm. 19F NMR
(282 MHz, DMSO-d6): δF ꢀ95.4 (m, 1F, F-5 py), ꢀ158.4
(m, 1F, F-6 py), ꢀ166.9 (m, 1F, F-2 py) ppm; and trace 6-
amino-4-(2-bromophenyl)-2-oxo-1-((perfluoropyridin-4-
yl)amino)-1,2-dihydropyridine-3,5-dicarbonitrile 8f, brown
ppm. 13C NMR (75 MHz DMSO-d6): δC 159.8 (C═O),
156.4 (pyridone-C), 156.0 (pyridone-C), 145.8 (Ar-C),
1
144.1 (dm, JCF = 230.4 Hz, C-6 py), 138.2 (m, C-2 py),
134.7
(Ar-C),
132.0
(Ar-CH),
131.1
(dm,
1JCF = 246.2 Hz, C-5 py), 130.0 (Ar-CH), 128.6 (Ar-
CH), 126.7 (Ar-CH), 115.6 (CN), 113.2 (CN), 85.7
(pyridone-C), 76.9 (pyridone-C) ppm. 19F NMR
(282 MHz, DMSO-d6): δF ꢀ96.3 (m, 1F, F-5 py),
ꢀ158.8 (m, 1F, F-6 py), ꢀ167.5 (m, 1F, F-2 py) ppm;
oil. IR (KBr): ν 3447 (N-H), 2217 (CN), 1640 (C═O) cmꢀ1
.
19F NMR (282 MHz, DMSO-d6): δF ꢀ97.6 (m, 2F, F-2,6
py), ꢀ156.0 (m, 2F, F-3,5 py) ppm.
1,3,4-Trifluoro-9-(2-nitrophenyl)-7-oxo-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile(7g).
and
trace
6-amino-4-(3-nitrophenyl)-2-oxo-1-
Potassium carbonate (0.414 g, 3 mmol), 1,6-diamino-
4-(2-nitrophenyl)-2-oxo-1,2-dihydropyridine-3,5-
((perfluoropyridin-4-yl)amino)-1,2-dihydropyridine-3,5-
dicarbonitrile 8h, 7%, brown solid; mp: 130–133°C. IR
(KBr): ν 3446 (N-H), 2216 (CN), 1646 (C═O) cmꢀ1 19F
.
dicarbonitrile 5g (0.296 g, 1 mmol), pentafluoropyridine 6
(0.169 g, 1 mmol), and CH3CN (8 mL), after refluxing for
40 h and using column chromatography (EtOAc/MeOH,
10:1), gave 1,3,4-trifluoro-9-(2-nitrophenyl)-7-oxo-7,11-
dihydro-5H-dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-
dicarbonitrile 7g, 45%; yellow solid; mp: 213–215°C.
(Found: C, 50.59; H, 1.33; N, 22.87; C18H6F3N7O3
requires: C, 50.84; H, 1.42; N, 23.05). IR (KBr): ν 3317
NMR (282 MHz, DMSO-d6): δF ꢀ98.3 (m, 2F, F-2,6
py), ꢀ147.3 (m, 1F, F-3,5 py) ppm.
1,3,4-Trifluoro-9-(4-nitrophenyl)-7-oxo-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile (7i).
Potassium carbonate (0.414 g, 3 mmol), 1,6-diamino-4-(4-
nitrophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile
5i (0.296 g, 1 mmol), pentafluoropyridine 6 (0.169 g,
1 mmol), and CH3CN (8 mL), after refluxing for 40 h and
using column chromatography (EtOAc/MeOH, 10:1),
gave 1,3,4-trifluoro-9-(4-nitrophenyl)-7-oxo-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile 7i,
33%; yellow solid; mp: 226–229°C. (Found: C, 50.60; H,
1.36; N, 22.90; C18H6F3N7O3 requires: C, 50.84; H, 1.42;
N, 23.05). IR (KBr): ν 3212 (NH), 3306 (N-H), 2223 (CN),
.
(N-H), 2224 (CN), 1627 (C═O) cmꢀ1 1H NMR
(300 MHz, DMSO-d6): δH 9.16 (NH), 8.37 (d, 1H,
3
3JHH = 8.2 Hz, Ar-H), 8.00 (t, 1H, JHH = 7.5 Hz, Ar-H),
3
7.90 (t, 1H, JHH = 7.6 Hz, Ar-H), 7.80 (d, 1H,
3JHH = 7.6 Hz, Ar-H) ppm. 13C NMR (75 MHz
DMSO-d6): δC 159.9 (C═O), 157.8 (pyridone-C), 157.6
1
(pyridone-C), 146.3 (Ar-C), 143.3 (dm, JCF = 233.1 Hz,
1
1630 (C═O) cmꢀ1. H NMR (300 MHz, DMSO-d6): δH
C-6 py), 137.8 (m, C-2 py), 135.3 (Ar-C), 132.2 (Ar-CH),
1
9.50 (NH), 8.40 (d, 2H, 3JHH = 8.6 Hz, Ar-H), 7.90 (d, 2H,
131.6 (dm, JCF = 252.9 Hz, C-5 py), 130.7 (Ar-CH),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. Ranjbar-Karimi, A. Darehkordi, F. Bahadornia, and A. Poorfreidoni
Vol 000
3JHH = 8.6 Hz, Ar-H) ppm. 13C NMR (75 MHz, DMSO-d6):
δC 159.0 (C═O), 157.8 (pyridone-C), 157.4 (pyridone-C),
148.7 (Ar-C), 140.6 (Ar-C), 130.0 (Ar-CH), 123.9 (Ar-
CH), 115.5 (CN), 114.8 (CN), 86.3 (pyridone-C), 74.3
(pyridone-C) ppm. 19F NMR (282 MHz, DMSO-d6): δF
ꢀ95.6 (m, 1F, F-53 py), ꢀ158.2 (m, 1F, F-6 py), ꢀ167.2
(m, 1F, F-2 py) ppm; and trace 6-amino-4-(4-nitrophenyl)-
2-oxo-1-((perfluoropyridin-4-yl)amino)-1,2-
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dihydropyridine-3,5-dicarbonitrile 8i, brown solid; mp:
203°C. IR (KBr): ν 3447 (N-H), 2217 (CN), 1640 (C═O)
cmꢀ1 19F NMR (282 MHz, DMSO-d6): δF –97.1 (m, 2F,
.
F-2,6 py), ꢀ156.0 (m, 2F, F-3,5 py) ppm.
1,3,4-Trifluoro-9-(4-fluorophenyl)-7-oxo-7,11-dihydro-5H-
dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-dicarbonitrile (7j).
Potassium carbonate (0.414 g, 3 mmol), 1,6-diamino-
4-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3,5-
[12] Banks, R. E.; Haszeldine, R. N.; Karsa, D. R.; Rickett, F. E.;
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dicarbonitrile 5j (0.269 g, 1 mmol), pentafluoropyridine 6
(0.169 g, 1 mmol), and CH3CN (8 mL), after refluxing for
45 h and using column chromatography (EtOAc/MeOH,
10:1), gave 1,3,4-trifluoro-9-(4-fluorophenyl)-7-oxo-7,11-
dihydro-5H-dipyrido[1,2-b:30,40-e][1,2,4]triazine-8,10-
dicarbonitrile 7j, 38%; yellow solid; mp: 227–230°C.
(Found: C, 54.08; H, 1.39; N, 20.85; C18H6F4N6O
requires: C, 54.28; H, 1.52; N, 21.10). IR (KBr): ν
1
3424 (NH), 2230 (CN), 1625 (C═O) cmꢀ1. H NMR
(300 MHz, DMSO-d6): δH 9.1 (NH), 7.62–7.68 (m, 2H,
Ar-H), 7.38–7.45 (m, 2H, Ar-H) ppm. 13C NMR
(75 MHz, DMSO-d6): δC 165.0 (C═O), 161.7
1
(pyridone-C), 159.2 (d, JCF = 173.6 Hz, Ar-C), 157.6
1
(pyridone-C), 143.3 (dm, JCF = 235.2 Hz, C-6 py), 138.4
1
(m, C-2 py), 131.4 (dm, JCF = 246.7 Hz, C-5 py), 130.8
3
4
(d, JCF = 8.85 Hz, Ar-CH), 130.7 (d, JCF = 3.2 Hz, Ar-
2
C), 116.0 (CN), 115.7 (CN), 115.5 (d, JCF = 51.2 Hz, Ar-
CH), 86.5 (pyridone-C), 74.7 (pyridone-C) pm. 19F NMR
(282 MHz, DMSO-d6): δF ꢀ95.1 (m, 1F, F-5 py), ꢀ110.0
(1F, Ar-CF), ꢀ157.8 (m, 1F, F-6 py), ꢀ166.7 (m, 1F, F-2
py) ppm; and trace 6-amino-4-(4-fluorophenyl)-2-oxo-1-
((perfluoropyridin-4-yl)amino)-1,2-dihydropyridine-3,5-
dicarbonitrile 8j, brown solid; mp: 200–202°C. IR (KBr): ν
3441 (N-H), 2215 (CN), 1651 (C═O) cmꢀ1 19F NMR
.
(282 MHz, DMSO-d6): δF –97.6 (m, 2F, F-2,6 py), ꢀ110.8
(1F, Ar-CF) ꢀ156.8 (m, 2F, F-3,5 py) ppm.
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Acknowledgment. The authors wish to thank Vali-e-Asr
University of Rafsanjan for partially funding this work.
SUPPORTING INFORMATION
REFERENCES AND NOTES
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
[1] Halpern, D. F.; Vernice, G. G. Chemistry of Organic Fluorine
CompoundsII;AmericanChemicalSociety:Washington,DC,1995,p.172.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet