Synthesis of Functionalized Hemi-1,2,4-triazinyl-[2,2′]-bipyridines via Telescoped Condensation of [2,2′]-bipyridinyl-6-carbonitrile

Article abstract of DOI:10.1002/jhet.2908

Partitioning of neutron-poisoning lanthanides from minor actinides in used nuclear fuel using liquid–liquid separation techniques with moderately soft Lewis basic heterocyclic scaffolds is an area of intense research focus. Nitrogen heterocycles have demo

Full text of DOI:10.1002/jhet.2908

Month 2017
Synthesis of Functionalized Hemi-1,2,4-triazinyl-[2,20]-bipyridines via
Telescoped Condensation of [2,20]-bipyridinyl-6-carbonitrile
*
Ryan P. Downs, Ai Lin Chin, Kayla M. Dean, and Jesse D. Carrick
Department of Chemistry, Tennessee Technological University, 55 University Drive, Cookeville, Tennessee 38505-0001,
USA
*
E-mail: jcarrick@tntech.edu
Received March 28, 2017
DOI 10.1002/jhet.2908
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
Partitioning of neutron-poisoning lanthanides from minor actinides in used nuclear fuel using liquid–
liquid separation techniques with moderately soft Lewis basic heterocyclic scaffolds is an area of intense
research focus. Nitrogen heterocycles have demonstrated potential for the selective separation of Am3+ from
Eu3+ in separations processes. Improved synthetic strategies are required to access more diversified
complexant scaffolds for further study. The present work describes an efficient synthetic strategy for the
preparation of functionalized [2,20]-bipyridinyl scaffolds using Pd catalysis to prepare the requisite starting
material and telescoped condensation to afford direct access to hemi-1,2,4-triazinyl-[2,20]-bipyridines with
aliphatic character and potentially greater solubility in less polar diluents. Synthetic method development,
optimization, and substrate scope are reported herein.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
the requisite 2,20-bipyridinylcarbonitrile and subsequent
telescoping of an intermediary hydrazonamide to afford
10 functionalized hemi-TBP complexants (six novel) in
the polar aprotic solvent 2-methyltetrahydrofuran.
Transmutation and recovery of radionuclides intrinsic to
used nuclear fuel continues to inspire significant effort.
The fundamental impetus for our interest in this area is
grounded in the hypothesis that moderately soft Lewis
basic complexants with the appropriate physical properties
can achieve selective separation of An(III) over Ln(III)
from used nuclear fuel on a kinetically viable time scale
with suitable distribution values [1]. While previously
prepared complexants successfully address some important
challenges, work over the last three decades has yet to
identify the ideal complexant [2]. Efforts in this laboratory
seek to develop streamlined synthetic methods [3] to
address complexant solubility challenges, in addition to
employing modular concepts for the rapid, convergent
construction of novel scaffolds [4].
The present study describes the preparation of hemi-
1,2,4-triazinyl-[2,20]-bipyridine (hemi-TBP) complexant
scaffolds as potential complexants for future investigation
in liquid–liquid separations. While the utilization of the
aforementioned scaffold has been described in separation
studies [5], a general synthetic approach has not been
disseminated. Highlights of the presented work include
Pd-catalyzed coupling of 6-bromo-2-pyridinecarbonitrile
and 2-bromopyridine using the Negishi coupling to afford
RESULTS AND DISCUSSION
Initial efforts sought to form the desired C–C bond
between a preactivated and unactivated derivative of
3-(6-bromopyridin-2-yl)-5,6-diphenyl-[1,2,4]-triazine to
afford
symmetric
and
unsymmetric
bis-1,2,4-
triazinyl-[2,20]-bipyridines. This end goal proved elusive.
A related goal focused on the synthesis of hemi-TBP
complexants leveraging the synthesis of carbonitrile 2
while incorporating less toxic reagents derived from the
pyridinyl zinc reagent 4, obtained from 2-bromopyridine,
via Negishi coupling with 5 (Scheme 1) [6]. The
exorbitant cost of 2 from commercial sources rendered its
synthesis of paramount importance on the path to
functionalized hemi-TBPs. Previous approaches to the
construction of the desired hemi-TBP scaffolds using
[2,20]bipyridinyl-6-carbonitrile
routinely
employ
oxidation of a pyridinyl N to the corresponding N-oxide
followed by functional group interconversion, and
cyanation with trimethylsilyl cyanide [7]. Alternative
© 2017 Wiley Periodicals, Inc.

R. P. Downs, A. L. Chin, K. M. Dean, and J. D. Carrick
Vol 000
Scheme 1. Synthetic approaches to the construction of [2,20]-bipyridinyl-2-carbonitrile.
procedures to the construction of 2 utilizing the Stille
coupling have also been reported [8]. The formation of 2
has also been accomplished by Duan [9] using reductive
Ni catalysis in the absence of ligand. We sought a direct
method leveraging Pd catalysis that did not involve
challenging reagent preformation [10] prior to execution
of the desired transformation. Inspired by the work of
Luzung and Yin [11], who demonstrated the formation
of various aryl heterocycles via Negishi coupling of
premetalated 2-bromopyridine and suitable aryl chlorides,
we sought to define or apply the aforementioned reaction
conditions toward the formation of 2.
formation conditions. Entry into these diversified hemi-
TBP scaffolds beyond those accessible from commercially
available 1,2-dicarbonyls was predicated on preparation of
the novel benzil reagents from 4,40-dibromobenzil
leveraging our recently published method for double
Suzuki–Miyaura cross-coupling of such substrates
(Scheme 2) [13]. The requisite 4,40-dialkylbenzils,
including novel examples 6, 8–9, were afforded in good to
excellent isolated yields over two steps in one reaction pot
from 4,40-dibromobenzil (Supporting Information).
With a viable synthetic pathway for the production of 2
and 6–9 realized, our focus shifted to optimizing access to
various hemi-TBP scaffolds. Thus, treatment of 2 with
hydrazine hydrate afforded the desired [2,20]-bipyridinyl
Treatment
of
2-bromopyridine
(3)
with
isopropylmagnesium chloride facilitated a metal-halogen
exchange reaction to afford a pyridinyl Grignard reagent,
which was transmetallated to the zinc reagent 4. Negishi
coupling of 5 using Dipalladium-tris-dibenzylideneacetone
[Pd2(dba)3] with XPhos afforded 60% conversion to the
desired 2,20-bipyridine 2. Additional optimization attempts
through catalyst and/or ligand screening did not improve
reaction outcome toward the production of 2. Further
optimization of the candidate system through solvent
screening, reactant concentration, order of addition, or
reaction temperature did not afford substantive advantages
over the listed conditions. Contemporary approaches to the
1
hydrazonamide 10. Analysis of 10 via H NMR confirmed
high levels of conversion in excess of 93 mol% via
integration of selected resonances. Hydrazonamide 10 was
directly telescoped to the condensation reaction without
further purification. An initial solvent screen for hemi-TBP
preparation was undertaken including THF, DMF, NMP,
and 2-MeTHF pursuant to our previously published work
using polar aprotic solvents, with 2-MeTHF emerging as
the ideal candidate solvent for this system. Dissolution of
10 and the requisite 1,2-dicarbonyl in 2-MeTHF at 80°C
afforded a homogeneous mixture, which was refluxed for
16 h to afford the desired complexants (11–20) (Table 1).
Complexants 11–14 and 19 were accessed from
commercially available 4,40-benzil reagents. Di-4-
alkylphenyl-1,2,4-triazinyl-[2,20]-bipyridines 15–18 as well
as 20 [3] required preparation of the 1,2-dicarbonyl
(Scheme 2). Isolated, purified yields ranged from 34% to
80% over two steps from 2 (entries 1–10). Interestingly,
construction of
2 using N-methyliminodiacetic acid
(MIDA) reagents for the formation of the desired [2,20]-
bipyridine substrate were also unsuccessful [12].
With a defined catalytic method in place for the formation
of the desired carbon–carbon bond in the hemi-TBP starting
material (2), we sought to evaluate the formation of the
requisite hydrazonamide and preliminary heterocycle
Scheme 2. Preparation of requisite 4,40-dialkyl benzils by Suzuki–Miyaura cross-coupling.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis of Functionalized Hemi-1,2,4-triazinyl-[2,20]-bipyridines via Telescoped
Condensation of [2,20]-bipyridinyl-6-carbonitrile
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

R. P. Downs, A. L. Chin, K. M. Dean, and J. D. Carrick
Vol 000
hemi-TBP complexants appear to display electronic
EXPERIMENTAL
All reagents were purchased from the US
environment sensitivity to heterocycle formation that was
previously encountered in earlier work from this lab [3],
whereby resonance donating substitutents, such as the 3,30-
OMe substituent in 19, inhibited the condensation reaction
leading to lower conversion of 10 and similarly lower
isolated yields presumably via suppression of the
electrophilicity of the 1,2-dione carbonyl. Synthesis of the
4,40-OMe constitutional isomer of 19 was attempted, but
resulted in incomplete conversion and a complex mixture
of materials unable to be separated chromatographically.
Although a decrease in efficiency of the heterocycle
synthesis with 4,40-alkyl benzils (15–17) beyond methyl
(14) was observed, presumably because of the inductively
electron-donating alkyl substituents, preparation of these
completely novel complexants was possible. Isolation and
purification of the complexant scaffolds was
straightforward and involved direct absorption of the crude
reaction mixture on silica gel followed by purification
using automated flash chromatography.
General.
chemical suppliers, stored according to published
protocols, and used as received unless indicated
otherwise. All experiments were performed in oven-dried
or flame-dried glassware under an inert atmosphere of Ar
except where indicated. Reaction progress was monitored
using thin-layer chromatography on glass-backed silica
gel plates and/or 1H-NMR analysis of crude reaction
mixtures. RF values for compounds that resulted in a
concentrically observed spot on normal phase silica gel
are reported using the conditions listed. All reported
yields listed are for pure compounds and corrected for
residual solvent, if applicable, from 1H NMR
spectroscopy unless otherwise indicated. Infrared spectral
1
data were acquired from the (form) listed. All H and 13C
NMR chemical shifts are reported using the δ scale and
are referenced to the residual solvent signal: CDCl3 (δ
1
7.26) or DMSO-d6 (δ 2.50) for H-NMR and chloroform
(δ 77.16), DMSO-d6 (δ 39.52) for 13C-NMR. Splittings
are reported as follows: (s) = singlet, (d) = doublet,
(t) = triplet, (dd) = doublet of doublets, (dt) = doublet of
triplets, (br) = broad, and (m) = multiplet. High-
resolution mass spectrometry (HRMS) data was obtained
utilizing electron impact (EI) ionization with a magnetic
sector (EBE trisector), double focusing-geometry mass
analyzer unless indicated otherwise.
CONCLUSIONS
In conclusion, we have described an efficient
preparation of various functionalized hemi-TBPs using a
Negishi-coupling
reaction
to
afford
[2,20]
bipyridinyl-6-carbonitrile, which was transformed to the
hemi-TBP via telescoped condensation to afford six
novel (Supporting Information) complexants (10 total)
over two steps via a unified approach without the use of
anhydrous hydrazine, discrete purification of the
For a general experimental procedure on the preparation
of 6–9, see [13].
[2,20]-Bipyridinyl-6-carbonitrile (2).
An oven-dried 8-
mL reaction vial equipped with a magnetic stir bar was
treated with 2-bromopyridine (0.388 g, 2.46 mmol, 1.50
intermediary
hydrazonamide,
or
recrystallization
protocols. Moreover, this general strategy was applicable
to the production of hemi-TBPs with various substituents
including those with resonance and inductive electron-
donating properties. Future work will ascertain the
solubility of prepared complexants in process-relevant
diluents followed by evaluation of the most promising
candidates in separation assays to study chemoselectivity
for complexation of Am3+ over Eu3+. Synthesis of these
important scaffolds could provide additional insight into
metal–ligand covalency related to the interaction of
moderately soft-N-donor complexants with the f-orbitals
of minor-actinide Lewis acids such as Am3+. Additional
efforts will center on defining experimental parameters
for the direct formation of the 2,20-bipyridine carbon–
carbon of bis-1,2,4-triazinyl-[2,20]-bipyridine bond via
cross-coupling of the appropriately functionalized
precursors in addition to the investigation of aryl–aryl
couplings to 3-(6-bromopyridin-2-yl)-5,6-diphenyl-[1,2,4]
triazine. Studies to address the current synthetic
limitations of the method are ongoing in this laboratory
and will be reported in due course.
equiv)
followed
by
dropwise
addition
of
isopropylmagnesium chloride-2.0M in THF (1.35 mL,
2.70 mmol, 1.65 equiv) at ambient temperature and
continued for 3 h upon which time a solution of ZnCl2-
2.0M in anhydrous THF (1.47 mL, 2.95 mmol, 1.80
equiv) was added followed by continuation at ambient
temperature for an additional 2 h. A 25-mL round-
bottom flask equipped with a magnetic stir bar was
charged in sequential order the catalyst (5 mol%),
ligand (10 mol%), and 6-bromopyridine-2-carbonitrile
(0.300 g, 1.64 mmol, 1.00 equiv) in the listed solvent
at 0.3M. The homogeneous mixture containing catalyst,
ligand, and 6-bromopyridine-2-carbonitrile was allowed
to precomplex for 0.5 hr upon which time the
transmetallated material in the auxiliary flask was
charged dropwise followed by reflux at the temperature
listed for 16 h. Afterwards, the crude reaction mixture
was filtered through Celite, and the cake was conditioned
with copious amounts of EtOAc. The filtrate was
transferred to a separatory funnel where the organic layer
was washed successively with a saturated NaHCO3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis of Functionalized Hemi-1,2,4-triazinyl-[2,20]-bipyridines via Telescoped
Condensation of [2,20]-bipyridinyl-6-carbonitrile
solution followed by a saturated NaCl solution, dried over
anhydrous Na2SO4, filtered, and then concentrated to
afford the crude compound, which was purified on silica
gel using automated flash column chromatography with
an EtOAc : hexanes gradient.
1,2-Bis-(4-butylphenyl)ethane-1,2-dione (6). RF = 0.62,
5% EtOAc : hexanes; MTBE : hexanes (gradient);
isolated yield 0.121 g, 70%; yellow-greenish oil; 1H
NMR (500 MHz, CDCl3): δ = 7.88 (dt, J = 1.9,
8.4 Hz, 4H), 7.30 (Br–d, J = 8.4 Hz, 4H), 2.68 (t,
J = 7.5 Hz, 4H), 1.64–1.58 (m, 4H), 1.36 (sextet,
J = 7.5, 10.0 Hz, 4H), 0.93 (t, J = 7.5 Hz, 6H); 13C
NMR (125 MHz, CDCl3): δ = 194.7, 151.1, 131.0,
130.2, 129.2, 36.0, 32.3, 22.4, 14.0; IR (ATR-CDCl3):
ῡmax = 3031, 2957, 2860, 1668, 1603, 1570, 1216,
1172, 845 cmꢀ1; HRMS (EI): m/z calculated for
C22H26O2: 322.1933; found 322.1935.
hexanes. The resulting solids were analyzed by 1H
NMR confirming consumption of the starting material
and were telescoped directly to the condensation step
in 2-methyl THF (0.5M) with the appropriate 1,2-
dicarbonyl (1.05 equiv) without further purification.
1H NMR (500 MHz, DMSO-d6): δ = 8.73–8.69 (m,
2H), 8.34 (dd, J = 1.0, 7.8 Hz, 1H), 8.01–7.96 (m,
2H), 7.91 (t, J = 7.8 Hz, 1H), 7.49 (ddd, J = 1.0,
4.5, 7.8 Hz, 1H).
6-(5,6-Diphenyl-[1,2,4]triazin-3-yl)-[2,20]bipyridinyl (11). EtOAc/
hexanes (gradient), yellow solid; mp = 172.8–176.4°C; 1H NMR
(500 MHz, CDCl3): δ = 8.81 (Br–d, J = 7.8 Hz, 1H), 8.75–
8.70 (m, 3H), 8.11–8.06 (m, 1H), 7.95–7.89 (Br–m, 1H),
7.77–7.73 (m, 2H), 7.70–7.66 (m, 2H), 7.50–7.37 (m, 7H);
13C NMR (125 MHz, CDCl3): δ = 160.8, 156.5, 156.1,
155.5, 152.6, 148.72, 148.7X (overlaps with 148.72), 138.3,
137.8, 135.9, 135.5, 131.0, 130.1, 130.0, 129.7, 128.83,
128.76, 124.5, 124.4, 123.1, 122.3; IR (ATR-CDCl3):
ῡmax = 3059, 2930, 2855, 1580, 1561, 1493, 1382, 1361,
768, 697 cmꢀ1; HRMS (EI): m/z calculated for C25H17N5:
387.1484; found: 387.1494.
1,2-Bis-(4-octylphenyl)ethane-1,2-dione (8).
RF = 0.82,
10% MTBE : hexanes; MTBE/hexanes (gradient);
1
isolated yield 0.150 g, 64%; yellow/green oil; H NMR
(500 MHz, CDCl3): δ = 7.88 (d, J = 8.4 Hz, 4H), 7.30
(d, J = 8.4 Hz, 4H), 2.67 (t, J = 7.5 Hz, 4H), 1.65–1.59
(m, 4H), 1.36–1.23 (m, 20H), 0.87 (t, J = 7.2 Hz, 6H);
13C NMR (125 MHz, CDCl3): δ = 194.7, 151.1, 131.0,
130.2, 129.2, 36.4, 32.0, 31.2, 29.5, 29.4, 29.3, 22.8,
14.2; IR (ATR-CDCl3): ῡmax = 3031, 2924, 2854,
1669, 1603, 1570, 1216, 1171, 886 cmꢀ1; HRMS (EI):
m/z calculated for C30H42O2: 434.1385; found:
434.1392.
6-[5,6-Bis-(4-fluorophenyl)-[1,2,4]triazin-3-yl]-[2,20]bipyridinyl
(12).
EtOAc/hexanes (gradient); pale green powder;
mp = 193.4–197.6°C; 1H NMR (500 MHz, CDCl3):
δ = 8.80 (d, J = 8.0 Hz, 1H), 8.78–8.73 (m, 2H), 8.71 (dd,
J = 1.0, 8.0 Hz, 1H), 8.11 (t, J = 8.0 Hz, 1H), 7.99–7.94
(m, 1H), 7.79–7.44 (m, 2H); C–F coupling = 2.5 Hz, 7.70–
7.65 (m, 2H); C–F coupling = 2.5 Hz, 7.45–7.41 (Br–m,
1H), 7.16–7.09 (m, 4H); 13C NMR (125 MHz, CDCl3):
δ = 165.6, 165.0, 163.6, 163.0, 160.8, 155.4, 154.9, 152.4,
148.6, 138.45, 138.4X (overlaps with 138.45), 132.3,
131.6, 131.4, 131.35, 124.7, 124.6, 123.4, 122.5, 116.3,
116.2; IR (ATR-CDCl3): ῡmax = 3062, 2932, 3855, 1603,
1,2-Bis-(4-phenethylphenyl)ethane-1,2-dione (9). RF = 0.42,
5% EtOAc : hexanes; MTBE/hexanes (gradient); isolated
yield 0.240 g, 90%; pale yellow/green solid; mp = 81.3–
83.7°C, 1H NMR (500 MHz, CDCl3): δ = 7.89 (dt,
J = 1.8, 8.4 Hz, 4H), 7.31–7.26 (m, 8H), 7.22–7.18 (m,
2H), 7.17–7.14 (m, 4H), 3.03–2.98 (m, 4H), 2.96–2.92
(m, 4H), 13C NMR (125 MHz, CDCl3): δ = 194.5,
149.8, 141.0, 131.3, 130.3, 129.3, 128.6, 128.56, 126.35,
38.4, 38.2; IR (ATR-CDCl3): ῡmax = 3027, 2926, 2858,
1581, 1514, 1493, 1382, 1362, 1232, 1160, 841, 783 cmꢀ1
;
HRMS (EI): m/z calculated for C25H15F2N5: 423.1296;
found: 423.1294.
6-[5,6-Bis-(4-bromophenyl)-[1,2,4]triazin-3-yl]-[2,20]
bipyridinyl (13). MeOH/DCM (gradient); brown solid;
mp = 202.0–206.0°C; 1H NMR (500 MHz, CDCl3):
δ = 8.86–8.75 (m, 3H), 8.72 (d, J = 8.0 Hz, 1H),
8.15–8.10 (Br–m, 1H), 8.05–7.97 (Br–m, 1H), 7.65–
7.54 (m, 8H), 7.52–7.43 (m, 1H); 13C NMR
(125 MHz, CDCl3): δ = 161.0, 155.6, 155.2, 154.9,
152.1, 149.0, 148.9X (overlaps with 149.0), 138.3,
137.49, 134.4, 134.1, 132.3, 132.27, 131.6, 131.1,
126.2, 125.0, 124.4, 124.36, 123.2, 122.0; IR (ATR-
CDCl3): ῡmax = 3058, 1582, 1563, 1487, 1471, 1380,
1360, 904, 727 cmꢀ1; HRMS (EI): m/z calculated for
C25H15Br2N5: 542.9694; found: 542.9706.
1667, 1602, 1570, 1217, 1172, 829, 748, 698 cmꢀ1
;
HRMS (EI): m/z calculated for C30H26O2: 418.1933;
found: 418.1927.
Hydrazonamide (10).
To an 8-mL reaction vial
equipped with a magnetic stirring bar at ambient
temperature was charged 2 (0.100 g, 0.55 mmol, 1.00
equiv). After dissolution in anhydrous EtOH (57 μL,
9.60M), the clear solution was cooled to 0°C treated
dropwise with hydrazine monohydrate (60–65%
hydrazine) (0.24 mL, 2.76 mmol, 5.00 equiv) and
continued for 1 h. The homogeneous mixture was
allowed to gradually warm to ambient temperature
and heated to 40°C for 12 h. Afterwards, the
heterogeneous mixture was filtered under vacuum at
ambient temperature to afford a white filter cake that
6-(5,6-Di-p-tolyl-[1,2,4]triazin-3-yl)-[2,20]bipyridinyl
(14).
EtOAc/hexanes (gradient); green-yellow solid;
mp = 198.4–204.0°C; 1H NMR (500 MHz, CDCl3):
δ = 8.80 (d, J = 8.0 Hz, 1H), 8.73–8.71 (m, 1H), 8.70–
8.65 (m, 2H), 8.07 (t, J = 8.0 Hz, 1H), 7.92–7.88 (m,
was conditioned with
a minimal amount of 0°C
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R. P. Downs, A. L. Chin, K. M. Dean, and J. D. Carrick
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1H), 7.67 (d, J = 8.2 Hz, 2H), 7.59 (d, J = 8.2 Hz, 2H),
7.39–7.35 (Br–m, 1H), 7.22 (d, J = 8.2 Hz, 2H), 7.20 (d,
J = 8.2 Hz, 2H), 2.46 (s, 3H), 2.40 (s, 3H); 13C NMR
(125 MHz, CDCl3): δ = 160.5, 156.3, 155.9, 155.64,
155.6X (overlaps with 155.64), 152.7, 149.0, 141.5,
140.0, 138.2, 137.7, 133.1, 132.8, 130.0, 129.53, 129.5X
(overlaps with 129.53), 129.46, 124.4, 124.3, 122.9,
122.2, 21.7, 21.6; IR (ATR-CDCl3): ῡmax = 3058, 3025,
2921, 2863, 1675, 1607, 1581, 1561, 1493, 1381, 1361,
146.5, 145.1, 138.2, 137.5, 133.3, 133.0, 130.1, 129.6,
128.9, 128.8, 124.32, 124.26, 122.8, 122.2, 36.01,
35.96, 32.02, 32.01, 31.31, 31.25, 29.61, 29.58, 29.5X
(overlaps with 29.58), 29.43, 29.40, 29.4X (overlaps
with 29.40), 22.82, 22.81, 14.26, 14.2X (overlaps with
14.26); IR (ATR-CDCl3): ῡmax = 3056, 2926, 2854,
1610, 1581, 1493, 1468, 1431, 1381, 782 cmꢀ1; HRMS
(EI): m/z calculated for C41H45N5: 611.3988; found:
611.3998.
821, 782 cmꢀ1
; HRMS (EI): m/z calculated for
6-[5,6-Bis-(4-phenethylphenyl)[1,2,4]triazin-3-yl]-[2,20]bipyridinyl
C27H21N5: 415.1797; found: 415.1791.
(18). EtOAc/hexanes (gradient); pale-yellow solid; 1H NMR
6-[5,6-Bis-(4-butylphenyl)-[1,2,4]triazin-3-yl]-[2,20]bipyridinyl
(500 MHz, CDCl3): δ = 8.98 (Br–s, 1H), 8.83 (Br–s, 1H),
8.76 (d, J = 8.0 Hz, 1H), 8.16 (Br–t, J = 8.0 Hz, 1H),
7.66–7.63 (m, 2H), 7.59–7.56 (m, 2H), 7.29–7.24 (m, 7H),
7.21–7.13 (m, 10H), 3.00–2.91 (m, 8H); 13C NMR
(125 MHz, CDCl3): δ = 160.6, 156.3, 155.9, 155.6, 152.7,
148.69, 148.6X (overlaps with 148.69), 145.12, 143.8,
141.5, 141.3, 138.2, 137.8, 133.6, 133.2, 130.1, 129.6,
129.0, 128.9, 128.7, 128.6, 128.51, 128.49, 126.2, 124.4,
124.3, 123.0, 122.3, 37.91, 37.87, 37.7, 37.6; IR (ATR-
CDCl3): ῡmax = 3056, 3026, 2924, 2859, 1609, 1580,
1562, 1495, 1382, 1361, 825, 783, 748, 699 cmꢀ1; HRMS
(EI): m/z calculated for C41H33N5: 595.2736; found:
595.2728.
(15).
MeOH/DCM (gradient); yellow oil; 1H NMR
(500 MHz, CDCl3): δ = 8.84 (d, J = 8.0 Hz, 1H),
8.77–8.69 (m, 3H), 8.09 (t, J = 8.0 Hz, 1H), 7.99–
7.93 (Br–s, 1H), 7.70–7.66 (m, 2H), 7.62–7.58 (m,
2H), 7.45–7.39 (m, 1H), 7.24–7.18 (m, 4H), 2.69–2.63
(m, 4H), 1.67–1.58 (m, 4H), 1.42–1.32 (m, 4H), 0.98–
0.91 (m, 6H); 13C NMR (125 MHz, CDCl3):
δ = 160.5, 156.4, 156.0, 155.4, 152.8, 148.3, 146.5,
145.1, 138.3, 133.3, 133.0, 130.1, 129.6, 128.9, 128.8,
124.5, 124.5X (overlaps with 124.5), 124.4, 124.4X
(overlaps with 124.4), 123.1, 123.0, 35.72, 35.67, 33.5,
33.4, 22.50, 22.46, 14.11, 14.08; IR (ATR-CDCl3):
ῡmax = 3060, 3027, 2956, 2930, 2859, 1609, 1581,
1493, 1467, 1381, 1360, 834, 782, 732 cmꢀ1; HRMS
(EI): m/z calculated for C33H33N5: 499.2736; found:
499.2730.
6-[5,6-Bis-(3-methoxy-phenyl)-[1,2,4]triazin-3-yl]-[2,20]
bipyridinyl (19).
EtOAc/hexanes (gradient); yellow solid;
mp = 134.2–138.8°C; 1H NMR (500 MHz, CDCl3):
δ = 8.92–8.77 (m, 3H), 8.73 (d, J = 8.0 Hz, 1H), 8.13 (t,
J = 8.0 Hz, 1H), 8.06–7.99 (Br–m, 1H), 7.54–7.45 (m,
1H), 7.35–7.28 (m, 5H), 7.20–7.15 (m, 1H), 7.05–6.97 (m,
2H), 3.79 (s, 3H), 3.75 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ = 160.8, 159.9, 159.7, 156.8, 156.2, 155.88,
155.81, 152.31, 149.16, 138.1, 137.1, 137.0, 136.7,
129.74, 129.7X (overlaps with 129.74), 124.23, 124.2,
122.8, 122.5, 122.2, 121.9, 117.2, 116.3, 114.9, 114.4,
55.45, 55.38; IR (ATR-CDCl3): ῡmax = 3065, 3003, 2966,
2835, 1601, 1581, 1502, 1487, 1465, 1379, 908, 781,
731 cmꢀ1; HRMS (EI): m/z calculated for C27H21N5O2:
447.1695; found: 447.1701.
6-{5,6-Bis-[4-(3,3-dimethylbutyl)phenyl]-[1,2,4]triazin-3-yl}-
[2,20]bipyridinyl (16).
MeOH/DCM (gradient); yellow
1
solid; mp = 125.6–130.6°C; H NMR (500 MHz, CDCl3):
δ = 8.82 (Br–d, J = 8.0 Hz, 1H), 8.76–8.67 (m, 3H), 8.08
(t, J = 8.0 Hz, 1H), 7.96–7.91 (m, 1H), 7.71–7.67 (m,
2H), 7.62–7.59 (m, 2H), 7.42–7.37 (m, 1H), 7.25–7.20
(m, 4H), 2.67–2.59 (m, 4H), 1.58–1.49 (m, 4H), 0.98 (s,
9H), 0.97 (s, 9H); 13C NMR (125 MHz, CDCl3):
δ = 160.1, 156.5, 156.0, 153.16, 153.1X (overlaps with
153.16), 147.3, 145.9, 138.76, 138.7X (overlaps with
138.76), 133.1, 132.8, 130.1, 129.6, 128.82, 128.77,
125.3, 124.9, 123.89, 123.8X (overlaps with 123.89),
46.02, 46.01, 31.4, 31.3, 30.77, 30.7X, 29.50, 29.48; IR
(ATR-CDCl3): ῡmax = 3060, 3027, 2953, 2865, 1610,
3-[2,20]Bipyridinyl-6-yl-5,5,8,8-tetramethyl-5,6,7,8-
tetrahydrobenzo[1,2,4]triazine
(20).
EtOAc/
hexanes (gradient); pale-yellow solid; mp = 196.7–
1581, 1562, 1493, 1472, 1382, 1364, 844, 823, 783 cmꢀ1
;
1
200.8°C; H NMR (500 MHz, CDCl3): δ = 8.77 (d,
HRMS (EI): m/z calculated for C37H41N5: 555.3362;
found: 555.3372.
J = 8.0 Hz, 1H), 8.71–8.69 (m, 1H), 8.61 (d,
J = 8.0 Hz, 1H), 8.52 (d, J = 8.0 Hz, 1H), 8.02 (t,
J = 8.0 Hz, 1H), 7.90–7.85 (m, 1H), 7.38–7.33 (m,
1H), 1.87 (s, 4H), 1.51 (s, 6H), 1.45 (s, 6H); 13C
NMR (125 MHz, CDCl3): δ = 164.5, 163.1, 160.9,
156.3, 155.8, 153.0, 149.0, 138.0, 137.2, 124.1,
123.8, 122.3, 121.9, 37.4, 36.6, 33.8, 33.3, 29.9,
29.3; IR (ATR-CDCl3): ῡmax = 2966, 2928, 2854,
6-[5,6-Bis-(4-octylphenyl)[1,2,4]triazin-3-yl]-[2,20]bipyridinyl
(17).
MeOH/DCM (gradient); yellow oil; 1H NMR
(500 MHz, CDCl3): δ = 8.80 (Br–d, J = 8.0 Hz, 1H),
8.74–8.71 (m, 1H), 8.71–8.65 (m, 2H), 8.07 (t,
J = 8.0 Hz, 1H), 7.94–7.88 (m, 1H), 7.70–7.67 (m, 2H),
7.61–7.58 (m, 2H), 7.40–7.36 (m, 1H), 7.23–7.18 (m,
4H), 2.68–2.62 (m, 4H), 1.68–1.59 (m, 4H), 1.37–1.22
(m, 20H), 0.91–0.86 (m, 6H); 13C NMR (125 MHz,
CDCl3): δ = 160.6, 156.4, 156.0, 155.8, 152.7, 148.9,
1582, 1560, 1520, 1474, 1423, 1369, 794 cmꢀ1
;
HRMS (EI): m/z calculated for C21H35N5:
345.1953; found: 345.1957.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis of Functionalized Hemi-1,2,4-triazinyl-[2,20]-bipyridines via Telescoped
Condensation of [2,20]-bipyridinyl-6-carbonitrile
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Acknowledgments. This work was supported by the Tennessee
Technological University Department of Chemistry. K.M.D.
acknowledges support from the TTU Undergraduate Research
and Creative Activity (URECA!) Team Grant program for the
2015–2016 academic year and the TTU Creative Inquiry
Summer Experience (CISE) program for summer fellowship
support (2016). Support from NSF-MRI 1531870 is gratefully
acknowledged for the acquisition of the university’s 500 MHz
multi-nuclear NMR spectrometer. Dr. Qiaoli Liang and Prof.
Kevin H. Shaughnessy (UA) are acknowledged for acquisition
of HRMS data and for helpful discussions, respectively.
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SUPPORTING INFORMATION
Additional Supporting Information may be found online
in the supporting information tab for this article.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet