Synthetic Access to Functionalized Dipolarophiles of Lewis Basic Complexant Scaffolds through Sonogashira Cross-Coupling

Article abstract of DOI:10.1021/acs.joc.8b01446

Soft Lewis basic complexants that facilitate selective removal of discrete ions resident in spent nuclear fuel can decrease repository volume and radiotoxicity and are of significant interest. Optimization of chelation efficacy is predicated on modular access to synthons to rapidly evaluate structure-activity relationships. The following work highlights efficient access to functionalized synthons for use as potential dipolarophiles in subsequent cycloaddition processes via Sonogashira coupling of 3-(6-bromo-pyridin-2-yl)-[1,2,4]triazine scaffolds. The 41 examples explored during method development evaluated electrophile and nucleophile diversity affording the desired coupled products in 31-96% isolated yield. Method optimization, substrate scope, a scale-up reaction, and downstream product functionalization are reported herein.

Full text of DOI:10.1021/acs.joc.8b01446

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Article
Synthetic Access to Functionalized Dipolarophiles of Lewis Basic
Complexant Scaffolds through Sonogashira Cross-Coupling
Sauradip Chaudhuri, and Jesse Dwayne Carrick
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01446 • Publication Date (Web): 17 Jul 2018
Downloaded from http://pubs.acs.org on July 17, 2018
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The Journal of Organic Chemistry
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Synthetic Access to Functionalized Dipolarophiles of Lewis Basic Com-
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Sauradip Chaudhuri and Jesse D. Carrick*
Department of Chemistry, Tennessee Technological University, 55 University Drive, Cookeville, TN 38505ꢀ0001
The authors dedicate this work in memory of TTU Professor Emeritus Scott H. Northrup (1951ꢀ2018)
Supporting Information Placeholder
ABSTRACT: SoftꢀLewis basic complexants that facilitate
selective removal of discrete ions resident in spent nuclear
fuel can decrease repository volume and radiotoxicity and
Pd(dppf)Cl2 (5 mol%),
R1
CuI (5 mol%),
R1
TEA (3 equiv)
R2
N
N
N
(1.5 equiv),
N
N
Br
are of significant interest. Optimization of chelation efficacy
is predicated on modular access to synthons to rapidly evalꢀ
uate structureꢀactivity relationships. The following work
highlights efficient access to functionalized synthons for use
as potential dipolarophiles in subsequent cycloaddition proꢀ
cesses via Sonogashira coupling of 3ꢀ(6ꢀBromoꢀpyridinꢀ2ꢀyl)ꢀ[1,2,4]triazine scaffolds. The fortyꢀone examples explored during
method development evaluated electrophile and nucleophile diversity affording the desired coupled products in 31–96% isolated
yield. Method optimization, substrate scope, a scaleꢀup reaction, and downstream product functionalization are reported herein.
N
R2
N
MTBE, 55 oC, 16 h
N
41 examples
(31-96%)
R1
R1
R1 = H, F, CH3, OCH3
R2 = alkyl, aryl, heteroaryl
INTRODUCTION
Table 1. Sonogashira Coupling Method Development
The Sonogashira coupling reaction1 has been widely employed
in contemporary organic synthesis towards the pursuit of terꢀ
restrial and oceanic natural products,2 heterocycles,3 and mateꢀ
rials.4 The overall mild reaction conditions, chemoselectivity,
and wide substrate scope enhance the applicability of the
transformation. Exploration of advanced scaffolds for liquidꢀ
liquid separations processes in the areas of spent nuclear fuel
(SNF)5 remediation and recovery of critical materials6 necessiꢀ
tates the continuous development of modular synthetic methꢀ
ods to expand the competency, selectivity, and efficiency of
complexant scaffolds beyond simple functional group interꢀ
conversions towards more efficacious species. Research in this
laboratory has focused on the preparation of softꢀLewis basic
complexant synthons for the formation of previously unexꢀ
plored constructs based on the pyridinylꢀ1,2,4ꢀtriazine motif
for use in minorꢀactinide separations from SNF. Recently, we
disclosed procedures to afford a variety of functionalized scafꢀ
folds with applications in liquidꢀliquid separations7 including
3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiarylꢀ[1,2,4]triazines for utiliꢀ
zation in SuzukiꢀMiyaura crossꢀcoupling8 as well as Pdꢀ
catalyzed diamination.9 Current focus areas include the develꢀ
opment of synthons for dipolar cycloaddition reactions leading
to the formation of unsymmetric complexant scaffolds.
Catalyst, Ligand
Base, Additive,
Ph
Ph
N
N
Ph
Ph
N
N
N
Br
N
N
N
Solvent (0.25 M),
Temp (oC), 16 h
1
2
temp
(°C)
conv
(%)a
entry
catalyst
ligand
base
additive
solvent
1
2
Pd2(dba)3
Pd(dba)2
ꢀꢀꢀꢀꢀ
ꢀꢀꢀꢀꢀ
TEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
TEA
DBU
ꢀꢀꢀꢀꢀ
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
ꢀꢀꢀꢀꢀ
ꢀꢀꢀꢀꢀ
CuI
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
80
80
80
80
80
80
80
80
80
55
55
55
55
55
55
74b
83b
3
Pd(dba)2
CyPFꢀtBu
ꢀꢀꢀꢀꢀ
34b
4
Pd(cod)Cl2
Pd(OAc)2
71b
5
RuPhos
ꢀꢀꢀꢀꢀ
71b
6
Pd(PPh3)2Cl2
Pd(MeCN)2Cl2
Pd(OAc)2
40b
7
ꢀꢀꢀꢀꢀ
70b
8
ꢀꢀꢀꢀꢀ
79b
9
Pd(dppf)2Cl2
Pd(dppf)2Cl2
Pd(dppf)2Cl2
Pd(dppf)2Cl2
Pd(dppf)2Cl2
Pd(dppf)2Cl2
Pd(dppf)2Cl2
ꢀꢀꢀꢀꢀ
87b
10
11
12
13
14
15
ꢀꢀꢀꢀꢀ
88b
ꢀꢀꢀꢀꢀ
99c (78)d
99c (51)d
0c
ꢀꢀꢀꢀꢀ
ꢀꢀꢀꢀꢀ
ꢀꢀꢀꢀꢀ
TEA
ꢀꢀꢀꢀꢀ
0c
0c
ꢀꢀꢀꢀꢀ
5 mol% catalyst, 10 mol% ligand (entries 3 and 5), 5 mol% CuI, in cyclopentyl methyl ether
(CPME) or methyl tertꢀbutyl ether (MTBE) as solvent. aConversion determined from integration
of select resonances in the 1H NMR spectrum without internal standard. b1.05 equiv of 4ꢀ
methylphenylacetylene used. c1.50 equiv of 4ꢀmethylphenylacetylene used. disolated, purified
yield. CyPFꢀtBu = 1ꢀdicyclohexylphosphinoꢀ2ꢀdiꢀtꢀbutylphosphinoethylferrocene
RESULTS AND DISCUSSION
The alkynyl moiety can be a participant in the Huisgen cyꢀ
cloaddition10 leading to the formation of 1,2,3ꢀtriazoles,11 in
addition to related processes, which facilitate access to 1,2ꢀ
pyrazoles.12 Pursuit of the aforementioned cycloadducts is
centered on foundational access to the requisite Sonogashira
coupling product through Pdꢀcatalysis. A systematic approach
to optimize the transformation for the desired application was
pursued which varied critical parameters (Table 1).
Initial definition of reaction conditions began with the evaluaꢀ
tion of Pd2(dba)3 and Pd(dba)2 entries 1 and 2, with 3ꢀ(6ꢀ
bromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiphenylꢀ[1,2,4]triazine,13 1ꢀethynylꢀ
4ꢀmethylbenzene, copper iodide, and triethylamine which
resulted in 74% and 83% conversion, respectively. Evaluation
of Pd(dba)2 with CyPFꢀtBu which Hartwig14 has demonstrated
for amination was successful in our hands with an amination
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reaction15 of the same scaffold (1), but resulted in poor perꢀ
Page 2 of 11
Table 2 describes the utility of various alkynes with different
1
formance in the current context (entry 3). The change in nuꢀ
cleophile in this transformation is postulated to have a marked
impact on desired product formation under these conditions. A
commonly employed catalyst for the Sonogashira coupling,
Pd(PPh3)Cl2 (entry 6), was moderately successful.16 Screening
of additional Pd(II) salts, entries 7−9 validated Pd(dppf)Cl2 as
the most potent catalyst system. Alternative ethereal solvents
were explored, including 1,4ꢀdioxane, 2ꢀmethylTHF, THF,
and MTBE. MTBE facilitated the formation of the desired
product 2 in marginally higher conversion, but with a better
impurity profile (entry 10). An increase in the alkyne loading
from 1.05 equiv relative to 1 (entry 10) to 1.50 equiv (entry
11) afforded quantitative formation of 2 and good isolated
yield. Base optimization with DBU (entry 12), DABCO,
DIPEA, or diisopropylamine, in addition to the assessment of
alternative copper salts, including copper acetate, proved unꢀ
fruitful. As part of due diligence, the appropriate control exꢀ
periments were performed highlighted by entries 13−15 and
resulted in no conversion. With a preliminary set of reaction
conditions defined for 4ꢀmethylphenyl acetylene, we set out to
evaluate the alkyne scope with 1 (Table 2).
electronic properties and functional groups towards the expanꢀ
sion of synthetic derivatives of 1. Aliphatic alkynes such as
octyne and decyne (entries 1−2) afforded the desired products
3 and 4 in good to excellent yield, respectively. Phenylacetyꢀ
lene (entry 3) and related derivatives (entries 4−8) provided
functionalized products in a consistent yield range with elecꢀ
tronꢀdonating substituents methyl (2), tertꢀbutyl (9), and
methoxy (6) affording the highest yields. Deactivating substiꢀ
tutents including nitrile and bromoꢀ (entries 7–8) proved comꢀ
petent nucleophiles in this transformation.17 Constitutional
isomers of 4ꢀmethylphenylacetylene, including the 3ꢀmethyl
(entry 10) and 2ꢀmethyl congeners were explored in the conꢀ
text of this work with the former providing the desired product
(10) in a lower yield and the latter affording no conversion
presumably due to steric interference during the catalytic cyꢀ
cle. A heteroaromatic alkyne in the case of 2ꢀethynylpyridine
afforded the lowest isolated yield of any substrate and alkyne
combination screened (entry 11). Silylated acetylenes were
successful, with the triisopropylsilylꢀ (12) and tertꢀ
butyldimethylsilylacetylene (13) derivatives which provide
access to synthetic equivalents to coupling with acetylene.18
More electronꢀrich amines in the case of BOC protected proꢀ
pargylamine (entry 14) yielded the desired product in good
isolated yield and proved superior to propargylamine, which
was unsuccessful presumably due to poisoning of the catalytic
system. Benzylpropargyl ether afforded 15 in 61% yield.
Similar to above, attempted coupling with 4ꢀpentynꢀ1ꢀol was
unsuccessful, whereas 1ꢀphenylpropꢀ2ꢀynꢀol provided the
desired coupling product in 59% yield (entry 16). The alkyne
scope with 1 affords numerous opportunities for further exploꢀ
ration of these functionalized synthons in the context of dipoꢀ
larophiles for cycloaddition reactions with relevant dipoles.
As processꢀrelevant diluents for liquidꢀliquid separations of
the minorꢀactinides from SNF continue to advance towards
more efficient systems it is often desirable to enhance the
nonpolarity of resident Lewis basic complexant scaffolds.
Pursuant to the aforementioned, we sought to investigate the
utility of the proposed method for the development of more
nonpolar complexant synthons (Table 3). The input materials
required to execute this series of examples, with the exception
of 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ(4ꢀfluoroꢀphenyl)ꢀ[1,2,4]
triazine, have previously been disclosed by us.19 Thus, 3ꢀ(6ꢀ
bromoꢀpyridinꢀ2ꢀyl)ꢀ5,5,8,8ꢀtetraꢀmethylꢀ5,6,7,8ꢀtetrahydroꢀ
benzo[1,2,4]triazine (entries 1–2), 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ
5,6ꢀbisꢀ[4ꢀ(3,3ꢀdimethylꢀbutyl)ꢀphenyl]ꢀ[1,2,4] triazine (enꢀ
tries 3, 5, 7, and 9), as well as the butyl derivative (entries 2, 4,
6, 8, and 10) afforded the desired coupling products in (37–
96%) isolated yield with the electronꢀrich example 21 affordꢀ
ing the highest yield of any substrate and alkyne combination
evaluated. Incorporation of the prepared complexants in
downstream processes will provide fundamental guidance on
important structureꢀactivity relationships for effective separaꢀ
tion systems involving polydentate, softꢀLewis basic moieties.
Alternative aromatic scaffolds were also attempted to ascerꢀ
tain the impact of different electronic combinations in the
transformation (Table 4). Utilization of decyne with 3ꢀ(6ꢀ
bromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiꢀpꢀtolylꢀ[1,2,4]triazine (entry 2)
afforded the highest isolated yield. The electronꢀwithdrawing
4,4’ꢀdifluorosubstituent with phenylacetylenes (entries 3−5),
as well as octyne (entry 7), resulted in satisfactory perforꢀ
mance. Complexant scaffolds bearing the 3,3’ꢀdimethoxyꢀ
1,2,4ꢀtriazinyl moiety have demonstrated efficacy in the sepaꢀ
ration of the minor actinide Am3+ from the neutronꢀpoisoning
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Alkyne Reaction Scopea
Pd(dppf)Cl2 (5 mol%),
CuI (5 mol%),
TEA (3 equiv)
Ph
N
N
Ph
Ph
N
N
(1.5 equiv),
R
N
Br
N
N
N
R
1
Ph
MTBE, 55 oC, 16 h
Product
Yieldb
Entry
Ph
Ph
N
N
3
4
(76)
(91)
1
2
N
N
n
3 n = 5
4 n = 7
5
2
6
7
8
(63)c
(77)c
(63)
(50)
(54)
3
4
5
6
7
8
5
R' = H
R' = CH3
R' = OCH3
R' = CN
R' = Br
2
6
7
8
Ph
N
N
N
N
Ph
Ph
N
N
R'
9
(75)
9
N
N
Ph
Ph
N
N
10
N
10 (51)
Ph
Ph
N
N
11 (31)c
11
12
N
N
N
N
Ph
Ph
N
N
N
12 (74)
Si(iPr)3
Ph
Ph
N
N
N
N
13
14
15
16
13 (55)
14 (73)
N
N
Si(CH3)2tBu
Ph
Ph
N
N
H
N
O
Ph
Ph
N
N
O
15 (61)
16 (59)
N
N
O
Ph
N
N
Ph
Ph
N
N
OH
Ph
N
Ph
a Reaction Conditions: 3-(6-Bromo-pyridin-2-yl)-5,6-diphenyl-[1,2,4]triazine (0.13 mmol),
Pd(dppf)Cl2 (0.007 mmol), CuI (0.007 mmol), TEA (0.39 mmol), Alkyne (0.20 mmol),
slurried in MTBE (0.25 M), and heated for 16 h. bIsolated, purified yield over one
synthetic step, c Average yield from 2 experiments.
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The Journal of Organic Chemistry
Table 4. Diversified Ar Complexant Scaffoldsa
Table 3. Diversified Complexant Scaffoldsa
Pd(dppf)Cl2 (5 mol%),
1
Pd(dppf)Cl2 (5 mol%),
CuI (5 mol%),
CuI (5 mol%),
R1
R1
2
3
4
5
6
7
8
9
TEA (3 equiv)
(1.5 equiv),
R
TEA (3 equiv)
N
N
N
N
R2
(1.5 equiv),
N
N
N
N
N
N
Br
N
N
Br
N
R
MTBE, 55 oC, 16 h
N
R2
N
MTBE, 55 oC, 16 h
N
Yieldb
Entry
Product
R2 = alkyl, aryl
Yieldb
R1
R1
R1 = F, CH3, OCH3
Entry
17 (37)
18 (73)
Product
1
2
N
N
N
27 (62)
28 (90)
1
2
N
17 R = F
N
N
R
18 R = OCH3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
N
27 R = 4-MePh
R
19 (67)e
3
N
28 R = (CH2)7CH3
N
O
Ph
F
N
N
29 (78)
30 (73)
31 (52)
3
4
5
N
N
N
N
29 R = H
R
30 R = F
F
N
4
20 (45)
31 R = OCH3
N
H3CO
32 (80)c
N
N
6
N
N
N
F
N
F
H3CO
N
5
21 (96)
F
F
N
N
N
N
7
33 (78)
N
N
5
N
N
OCH3
N
N
22 (80)
6
N
N
8
9
34 (55)
35 (58)
N
N
N
34 R = F
R
35 R = OCH3
N
OCH3
N
7
23 (58)
N
N
a Reaction Conditions: 3-(6-Bromo-pyridin-2-yl)-[1,2,4]triazinyl scaffold (0.13 mmol),
Pd(dppf)Cl2 (0.007 mmol), CuI (0.007 mmol), TEA (0.39 mmol), Alkyne (0.20 mmol),
slurried in MTBE (0.25 M), and heated for 16 h. bIsolated, purified yield over one
synthetic step, c Average yield from 2 experiments.
donating functionality were screened leading to the examples
highlighted in Table 5.
N
N
8
24 (65)
N
N
Si(iPr)3
Table 5 outlines the efficacy of the developed method for
acetyl, formyl, cyanoꢀ, and methyl bromopyridine substrates
with yields ranging from 40−84%. Interestingly, it was obꢀ
served that the oxidative addition into the heterocycle CꢀBr
bond occurred preferentially to selfꢀreaction or oligomerizaꢀ
N
N
9
25 (55)
26 (67)
N
N
Si(CH3)2tBu
Table 5. Pyridine Substrate Scopea,b
Pd(dppf)Cl2 (5 mol%),
R
R
CuI (5 mol%), TEA (3 equiv)
(1.5 equiv),
R
N
N
Br
N
10
N
R
MTBE, 55 oC, 16 h
N
N
R = CH3, EWD
O
O
a Reaction Conditions: 3-(6-Bromo-pyridin-2-yl)-[1,2,4]triazinyl scaffold (0.13 mmol),
Pd(dppf)Cl2 (0.007 mmol), CuI (0.007 mmol), TEA (0.39 mmol), Alkyne (0.20 mmol),
slurried in MTBE (0.25 M), and heated for 16 h. bIsolated, purified yield over one
synthetic step, c Average yield from 2 experiments.
NC
N
N
37 (56)
N
H
38 (58)
36 (84)
O
lanthanides20 which preclude incorporation into advanced
fuels for nuclear reactors through the partition and transmutaꢀ
tion strategy.21 Entries 8−9 with 1ꢀethynylꢀ4ꢀflouroꢀ as well as
1ꢀethynylꢀ4ꢀmethoxybenzene resulted in the production of 34
and 35 in 55% and 58% yield, respectively. Interested in evalꢀ
uating the suitability of standard functionalized bromoꢀ
pyridines for the method scope beyond pyridinylꢀ1,2,4ꢀ
triazines, a series of substrates with electronꢀwithdrawing and
H
N
N
N
O
41 (40)
40 (40)
39 (57)
Br
Br
a Reaction Conditions: 6-bromopyridine derivative (0.13 mmol), Pd(dppf)Cl2 (0.007
mmol), CuI (0.007 mmol, 5 mol%), TEA (0.39 mmol), Alkyne (0.20 mmol), slurried in
MTBE (0.25 M), and heated for 16 h. bIsolated, purified yield over one synthetic step.
3
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Page 4 of 11
tion of the 1ꢀethynylꢀ4ꢀbromobenzene nucleophile in the cases
silica gel are reported using the conditions listed. All reported
of 39 and 41. Homocoupled Glaser22 products, a potential
byproduct of the Sonogashira coupling, were not observed in
the aforementioned cases or, with product 8. The modest
yields were attributed more to instability during chromatoꢀ
graphic purification and less to unwanted side reactions. The
1,2,4ꢀtriazinylꢀmoiety appears to bear little influence on the
selective oxidative addition into the CꢀBr bond of the pyridiꢀ
nyl moiety based on the outcome of these competition experiꢀ
ments other than to potentially enhance the electrophilicity of
this position. Products 8, 39, and 41 afford strategic opportuniꢀ
ties for additional functionalization.
1
2
3
4
5
6
7
8
yields listed are for pure compounds and corrected for residual
1
solvent, if applicable, from H NMR spectroscopy unless othꢀ
erwise indicated. Melting points are for a single experiment
1
and are uncorrected. All H and 13C NMR data was acquired
from a 500 MHz multinuclear spectrometer with broadꢀband
N2 cryoprobe. Chemical shifts are reported using the δ scale
and are referenced to the residual solvent signal: CDCl3 (δ
1
7.26), C6D6 (7.16) for H NMR and CDCl3 (δ 77.15), C6D6
(128.06) for 13C NMR. 13C NMR spectra were corrected for
ringdown using linear back prediction. Splittings are reported
as follows: (s) = singlet, (d) = doublet, (pent) = pentet, (t) =
triplet, (dd) = doublet of doublets, (dt) = doublet of triplets,
(br) = broad, and (m) = multiplet. Infrared spectral data was
acquired from the (form) listed. High resolution mass specꢀ
trometry (HRMS) data was obtained utilizing electron impact
ionization (EI) with a magnetic sector (EBE trisector), double
focusingꢀgeometry mass analyzer.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
A tenfold scaleꢀup experiment over initial screening pursuꢀ
ant to the conditions outlined in Table 1 for 16 above was
executed and produced similar results to the development
scale experiment (Scheme 1). Downstream functionalization
of prepared synthons was also attempted (Scheme 2). Suzukiꢀ
Miyaura crossꢀcoupling of 8 and potassium 3,3ꢀdimethylbutyl
trifluoroborate23 afforded the derivatized product 42. Pdꢀ
catalyzed amination of 8 was also successful, but purification
accelerated decomposition of aminated analogues of 42.
For an experimental procedure towards the preparation of 3ꢀ
(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiphenylꢀ[1,2,4]triazine used for
the construction of 2–16 please see reference 8(a). The
synthons required for 17–18 and 27–28 also appear in referꢀ
ence 8(a). For the bisꢀ3,3’ꢀdimethylbutylꢀ and bisꢀbutyl funcꢀ
tionalized scaffolds used with 19−26, as well as scaffolds used
to afford 32 and 34–35, please see reference 15.
Scheme 1. Tenfold Scale-Up Experiment
Pd(dppf)Cl2 (5 mol%),
CuI (5 mol%),
TEA (3 equiv)
(1.5 equiv),
R
Ph
Ph
N
N
Preparation of starting material for products 29−31; 33.
3ꢀ(6ꢀbromopyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ(4ꢀfluoroꢀphenyl)ꢀ[1,2,4]
triazine. For a general procedure for the formation of 6ꢀ
bromoꢀpyridinylꢀ2ꢀyl hydrazonamide please refer to reference
8(a). A 25 mL round bottom flask equipped with a magnetic
stir bar was charged with the requisite hydrazonamide (0.200
g, 0.93 mmol, 1.00 equiv) in anhydrous DMF (6.0 mL, 0.11
M). To the resulting slurry was added 4,4’ꢀdifluorobenzil
(0.229 g, 0.93 mmol, 1.00 equiv) in one portion followed by
heating at 66 °C for 18 hours. Afterwards, the mixture was
cooled to ambient temperature, absorbed on silica gel, and
purified using automated flashꢀcolumn chromatography. Rf =
0.65, 33% EtOAc:hexanes; eluent, EtOAc/hexanes (gradient);
isolated yield 0.272 g, 69%; greenish yellowꢀcolored solid;
melting point = 180.5–182.7 °C; 1H NMR (500 MHz, CDCl3):
δ = 8.63 (d, J = 7.6 Hz, 1H), 7.79 (t, J = 7.8 Hz, 1H),
7.75−7.68 (m, 3H), 7.66−7.62 (m, 2H), 7.15−7.06 (m, 4H);
13C NMR (125 MHz, CDCl3): δ = 165.4 (d, J = 76.9 Hz),
163.4 (d, J = 76.9 Hz), 163.1, 159.8, 155.6, 155.1, 153.8,
143.1, 139.4, 132.4 (d, J = 8.3 Hz), 131.7 132.4 (d, J = 8.3
Hz), 131.4 (d, J = 3.8 Hz), 131.2 (d, J = 3.1 Hz), 130.4, 123.1,
116.3 (d, J = 9.8 Hz), 116.2 (d, J = 9.3 Hz); IR (ATRꢀCDCl3):
ῡmax = 3073, 2973, 2934, 1601, 1575, 1557, 1512, 1376, 1359,
1226, 1158, 839, 797, 742 cm−1; HRMS (EI): m/z: [M]+ Calcd
for C20H11BrF2N4 424.0135; Found: 424.0128.
General Procedure for Pd-Catalyzed Sonogashira Reac-
tion of 3-(6-bromo-pyridin-2-yl)-[1,2,4]triazinyl Scaffolds:
To an 8 mL reaction vial equipped with a magnetic stir bar at
ambient temperature was charged Pd(dppf)Cl2 (5 mol%), CuI
(5 mol%), TEA (3 equiv), the requisite alkyne (1.5 equiv) in
anhydrous MTBE (0.25 M). The resulting slurry was heated
at 55 °C for the time indicated upon which time the crude reꢀ
action mixture was concentrated under reduced pressure at
ambient temperature to remove the TEA. The resulting darkꢀ
brown residue was partitioned between EtOAc (5 mL) and
water (2 mL). The organic layer was separated and the aqueꢀ
ous layer was backꢀextracted with two additional 5 mL porꢀ
tions of EtOAc. The combined organic layers were dried over
anhydrous Na2SO4, filtered, and then concentrated to afford
N
1
OH
MTBE, 55 oC, 16 h
N
16
Ph
1.3 mmol scale
56.1%
Scheme 2. Suzuki-Miyaura Cross-Coupling
Pd(OAc)2 (5 mol%),
RuPhos (10 mol%)
R3BF3K (2.1 equiv),
Ph
Ph
N
N
Cs2CO3 (3 equiv)
N
8
N
42
Tol:H2O (4:1),
115 oC, 16 h, (27%)
CONCLUSION
In summary, we have described a synthetic method to access
Sonogashira coupling products of a variety of functionalized
3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ[1,2,4]triazine scaffolds leading to
the formation of 41 examples in 31−96% isolated yield. The
method is moderately scalable and allows entry into numerous
structurally diverse possibilities. Additionally, these experiꢀ
ments have highlighted the selectivity of oxidative addition at
the CꢀBr bond of the pyridinyl scaffold preferentially to the Cꢀ
Br bond of 1ꢀethynylꢀ4ꢀbromobenzene. Access to these diverꢀ
sified synthons will afford opportunities to prepare advanced,
unsymmetric complexants with alternative heterocycle conꢀ
structs for potential use in liquidꢀliquid separations of SNF or
in the area of polyconjugated materials. Studies towards these
synthetic goals are ongoing in our laboratory and will be reꢀ
ported in due course.
EXPERIMENTAL SECTION
General Methods. All reagents were purchased from U.S.
chemical suppliers, stored according to published protocols,
and used as received unless indicated otherwise. All experiꢀ
ments were performed in ovenꢀ or flameꢀdried glassware. Reꢀ
action progress was monitored using thinꢀlayer chromatogꢀ
1
raphy on glassꢀbacked silica gel plates and/or H NMR analyꢀ
sis of crude reaction mixtures. Rf values for compounds that
resulted in a concentrically observed spot on normal phase
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The Journal of Organic Chemistry
135.4, 132.3, 131.0, 130.2, 130.0, 129.7, 129.2, 129.1, 128.8,
the crude mixture which was absorbed on silica gel and puriꢀ
1
2
3
4
5
6
7
8
fied using automated flash column chromatography under the
discrete conditions for each described compound to afford the
pure compound in the listed yield.
128.7, 128.5, 123.4, 122.4, 90.2, 88.9; IR (ATRꢀCDCl3): ῡmax
= 3052, 2234, 1577, 1562, 1492, 1411, 1358, 812, 775, 749,
695, 533 cm−1; HRMS (EI): m/z: [M]+ Calcd for C28H18N4
410.1531; Found 410.1537.
5,6ꢀDiphenylꢀ3ꢀ(6ꢀpꢀtolylethynylꢀpyridinꢀ2ꢀyl)ꢀ[1,2,4]triazꢀ
ine (2). Prepared according to the general procedure discussed
above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiphenylꢀ[1,2,4]
triazine and 1ꢀethynylꢀ4ꢀmethylꢀbenzene, Rf = 0.25, 33%
EtOAc:hexanes; eluent, EtOAc/hexanes (gradient); isolated
yield 0.0418 g, 76%; peachꢀcolored solid; melting point =
209.0–211.4 °C; 1H NMR (500 MHz, CDCl3): δ = 8.61 (d, J =
7.8 Hz, 1H), 7.92 (brꢀt, J = 7.8 Hz, 1H), 7.75−7.69 (m, 3H),
7.65 (d, J = 7.7 Hz, 2H), 7.54 (d, J = 7.8 Hz, 2H), 7.48−7.34
(m, 6H), 7.19 (d, J = 7.8 Hz, 2H), 2.39 (s, 3H); 13C NMR (125
MHz, CDCl3): δ = 160.5, 156.6, 156.4, 153.4, 144.6, 139.5,
137.3, 135.7, 135.4, 132.2, 130.9, 130.2, 129.9, 129.7, 129.3,
129.0, 128.8, 128.7, 123.1, 119.3, 90.5, 88.4, 21.7; IR (ATRꢀ
CDCl3): ῡmax = 3054, 3028, 2238, 1578, 1512, 1564, 1360,
822, 813, 775, 697, 533 cm−1; HRMS (EI): m/z: [M]+ Calcd
for C29H20N4 424.1688; Found: 424.1690.
3ꢀ[6ꢀ(4ꢀMethoxyꢀphenylethynyl)ꢀpyridinꢀ2ꢀyl]ꢀ5,6ꢀdiphenylꢀ
[1,2,4]triazine (6). Prepared according to the general proceꢀ
dure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀ
diphenylꢀ[1,2,4]triazine and 1ꢀethynylꢀ4ꢀmethoxybenzene, Rf
= 0.25, 33% EtOAc:hexanes; eluent, EtOAc/hexanes (gradiꢀ
ent); isolated yield 0.0360 g, 63%; offꢀwhite; melting point =
199.6–201.5 °C; 1H NMR (500 MHz, CDCl3): δ = 8.61 (d, J =
7.9 Hz, 1H), 7.92 (brꢀt, J = 7.9 Hz, 1H), 7.73 (brꢀd, J = 7.8 Hz,
2H), 7.69 (brꢀd, J = 7.7 Hz, 1H), 7.65 (brꢀd, J = 7.8 Hz, 2H),
7.60 (brꢀd, J = 8.0 Hz, 2H), 7.49−7.33 (m, 6H), 6.91 (d, J =
8.0 Hz, 2H), 3.85 (s, 3H); 13C NMR (125 MHz, CDCl3): δ =
160.5, 160.4, 156.7, 156.5, 153.4, 144.7, 137.4, 135.7, 135.5,
133.9, 131.0, 130.3, 130.0, 129.8, 128.9, 128.8, 128.7, 123.0,
114.5, 90.7, 87.9, 55.5; IR (ATRꢀCDCl3): ῡmax = 3073, 2906,
2839, 2210, 1605, 1575, 1564, 1511, 1358, 1243, 826, 776,
701, 695 cm−1; HRMS (EI): m/z: [M]+ Calcd for C29H20N4O
440.1637; Found 440.1633.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3ꢀ(6ꢀOctꢀ1ꢀynylꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiphenylꢀ[1,2,4]triazine
(3). Prepared according to the general procedure discussed
above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiphenylꢀ[1,2,4]
triazine and 1ꢀoctyne, Rf = 0.62, 33% EtOAc:hexanes; eluent,
EtOAc/hexanes (gradient); isolated yield 0.0413 g, 76%; offꢀ
4ꢀ[6ꢀ(5,6ꢀDiphenylꢀ[1,2,4]triazinꢀ3ꢀyl)ꢀpyridinꢀ2ꢀylethynyl]
ꢀbenzonitrile (7). Prepared according to the general procedure
discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiphenylꢀ
[1,2,4]triazine and 4ꢀethynylbenzonitrile, Rf = 0.15, 33%
EtOAc:hexanes; neutral alumina; eluent, EtOAc/hexanes (graꢀ
dient); isolated yield 0.0281 g, 50%; brown solid; melting
1
white solid; melting point = 117.3–119.8 °C; H NMR (500
MHz, CDCl3): δ = 8.54 (dd, J = 7.9 Hz, 0.9 Hz, 1H), 7.84 (t, J
= 7.9 Hz, 1H), 7.71−7.67 (m, 2H), 7.64−7.60 (m, 2H), 7.54
(dd, J = 7.8, 0.9 Hz, 1H), 7.44−7.31 (m, 6H), 2.46 (t, J = 7.2
Hz, 2H), 1.64 (t, J = 7.2 Hz, 2H), 1.51−1.43 (m, 2H),
1.37−1.26 (m, 4H), 0.93−0.85 (m, 3H); 13C NMR (125 MHz,
CDCl3): δ = 160.6, 156.5, 156.3, 153.2, 144.9, 137.1, 135.7,
135.4, 130.8, 130.2, 129.9, 129.7, 128.7, 128.6, 128.57, 122.8,
92.3, 80.6, 31.5, 28.8, 28.4, 22.6, 19.6, 14.2; IR (ATRꢀ
CDCl3): ῡmax = 3061, 3029, 2925, 2856, 2229, 1579, 1564,
1412, 1357, 1178, 811, 775, 701, 694 cm−1; HRMS (EI): m/z:
[M]+ Calcd for C28H26N4 418.2157; Found 418.2144.
1
point = 216.5–220.6 °C; H NMR (500 MHz, CDCl3): δ =
8.69 (d, J = 7.9 Hz, 1H), 7.98 (t, J = 7.9 Hz, 1H), 7.79−7.60
(m, 9H), 7.50−7.34 (m, 6H); 13C NMR (125 MHz, CDCl3): δ =
160.3, 156.8, 156.5, 153.8, 143.5, 137.6, 135.6, 135.3, 132.7,
132.3, 131.1, 130.2, 130.1, 129.7, 129.3, 128.8, 128.7, 127.3,
124.0, 118.5, 112.5, 92.7, 87.9; IR (ATRꢀCDCl3): ῡmax = 3066,
2921, 2228, 1601, 1578, 1566, 1503, 1495, 1359, 816, 772,
736, 724, 698 cm−1; HRMS (EI): m/z: [M]+ Calcd for C29H17N5
435.1484; Found 435.1487.
3ꢀ(6ꢀDecꢀ1ꢀynylꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiphenylꢀ[1,2,4]triazine
(4). Prepared according to the general procedure discussed
above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiphenylꢀ[1,2,4]
triazine and 1ꢀdecyne, Rf = 0.48, 33% EtOAc:hexanes; eluent,
EtOAc/hexanes (gradient); isolated yield 0.0455g, 78%;
3ꢀ[6ꢀ(4ꢀBromoꢀphenylethynyl)ꢀpyridinꢀ2ꢀyl]ꢀ5,6ꢀdiphenylꢀ
[1,2,4]triazine (8). Prepared according to the general proceꢀ
dure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀ
diphenylꢀ[1,2,4]triazine and 1ꢀbromoꢀ4ꢀethynylbenzene, Rf =
0.48, 33% EtOAc:hexanes; eluent, EtOAc/hexanes (gradient);
isolated yield 0.0341 g, 54%; brown solid; melting point =
1
brown solid; melting point = 101.1–104.2 °C; H NMR (500
1
MHz, CDCl3): δ = 8.55 (dd, J = 7.9, 0.8 Hz, 1H), 7.86 (t, J =
7.9 Hz, 1H), 7.73−7.68 (m, 2H), 7.66−7.61 (m, 2H), 7.55 (dd,
J = 7.9, 0.8 Hz, 1H), 7.47−7.33 (m, 6H), 2.47 (t, J = 7.2 Hz,
2H), 1.66 (pent, J = 7.2 Hz, 2H), 1.51−1.43 (m, 2H),
1.37−1.24 (m, 8H), 0.92−0.86 (m, 3H); 13C NMR (125 MHz,
CDCl3): δ = 160.6, 156.6, 156.4, 153.3, 145.0, 137.8, 135.7,
135.5, 130.9, 130.2, 129.9, 129.7, 128.8, 128.7, 128.6, 122.8,
92.3, 80.6, 32.0, 29.3, 29.28, 29.21, 28.5, 22.8, 19.6, 14.2; IR
(ATRꢀCDCl3): ῡmax = 3058, 2923, 2858, 2229, 1579, 1564,
1454, 1445, 1356, 812, 769, 694 cm−1; HRMS (EI): m/z: [M]+
Calcd for C30H30N4 446.2470; Found 446.2486.
221.0–223.0 °C; H NMR (500 MHz, CDCl3): δ = 8.66 (brꢀd,
J = 6.5 Hz, 1H), 7.98 (brꢀs, 1H), 7.77−7.68 (m, 3H), 7.65 (brꢀ
d, J = 7.7 Hz, 1H), 7.53 (brꢀs, 4H), 7.48−7.34 (m, 6H); 13C
NMR (125 MHz, CDCl3): δ = 160.1, 156.8, 156.5, 153.3,
143.7, 137.9, 135.6, 135.3, 133.8, 131.9, 131.0, 130.3, 130.0,
129.7, 129.2, 128.8, 128.7, 123.8, 123.6, 121.2, 90.0, 89.5; IR
(ATRꢀCDCl3): ῡmax = 3054, 1577, 1564, 1488, 1360, 1009,
826, 776, 698 cm−1; HRMS (EI): m/z: [M]+ Calcd for
C28H17BrN4 488.0637; Found 488.0628.
3ꢀ[6ꢀ(4ꢀtertꢀButylꢀphenylethynyl)ꢀpyridinꢀ2ꢀyl]ꢀ5,6ꢀ
diphenylꢀ[1,2,4]triazine (9). Prepared according to the general
procedure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀ
diphenylꢀ[1,2,4]triazine and 1ꢀtertꢀbutylꢀ4ꢀethynylbenzene, Rf
= 0.39, 33% EtOAc:hexanes; eluent, EtOAc/hexanes (gradiꢀ
ent); isolated yield 0.0452 g, 75%; offꢀwhite solid; melting
5,6ꢀDiphenylꢀ3ꢀ(6ꢀphenylethynylꢀpyridinꢀ2ꢀyl)ꢀ[1,2,4] triaꢀ
zine (5). Prepared according to the general procedure disꢀ
cussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiphenylꢀ
[1,2,4]triazine and ethynylbenzene, Rf
=
0.55, 33%
1
EtOAc:hexanes; eluent, EtOAc/hexanes (gradient); isolated
yield 0.0413 g, 77%; brown solid; melting point = 208.5–
point = 173.1–176.4 °C; H NMR (500 MHz, CDCl3): δ =
8.61 (d, J = 7.9 Hz, 1H), 7.92 (t, J = 7.9 Hz, 1H), 7.75−7.69
(m, 3H), 7.67−7.63 (m, 2H), 7.61−7.57 (m, 2H), 7.47−7.34
(m, 8H), 1.34 (s, 9H); 13C NMR (125 MHz, CDCl3): δ =
160.6, 156.7, 156.4, 153.5, 152.5, 144.7, 137.3, 135.7, 135.5,
132.1, 131.0, 130.2, 130.0, 129.7, 129.0, 128.8, 128.7, 125.6,
1
213.8 °C; H NMR (500 MHz, CDCl3): δ = 8.64 (d, J = 7.5
Hz, 1H), 7.94 (brꢀt, J = 7.5 Hz, 1H), 7.76−7.69 (m, 3H),
7.67−7.62 (m, 4H), 7.49−7.35 (m, 9H); 13C NMR (125 MHz,
CDCl3): δ = 160.5. 156.7, 156.4, 153.5, 144.4, 137.5, 135.7,
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123.1, 119.4, 90.5, 88.5, 35.0, 31.3; IR (ATRꢀCDCl3): ῡmax
=
3062, 2963, 2866, 2213, 1580, 1564, 1493, 1443, 1358, 831,
813, 765, 695 cm−1; HRMS (EI): m/z: [M]+ Calcd for C32H26N4
466.2157; Found: 466.2151.
HRMS (EI): m/z: [M−CH3]+ Calcd for C28H28N4Si 448.2083;
Found 433.1865.
{3ꢀ[6ꢀ(5,6ꢀDiphenylꢀ[1,2,4]triazinꢀ3ꢀyl)ꢀpyridinꢀ2ꢀyl]ꢀpropꢀ
1
2
3
4
5
6
7
8
2ꢀynyl}ꢀcarbamic acid tertꢀbutyl ester (14). Prepared accordꢀ
ing to the general procedure discussed above with 3ꢀ(6ꢀbromoꢀ
pyridinꢀ2ꢀyl)ꢀ5,6ꢀdiphenylꢀ[1,2,4]triazine and propꢀ2ꢀynylꢀ
carbamic acid tertꢀbutyl ester, Rf = 0.12, 33% EtOAc:hexanes;
neutral alumina; eluent, EtOAc/hexanes (gradient); isolated
yield 0.0441 g, 73%; yellow solid; melting point = 82.8–86.5
°C; 1H NMR (500 MHz, CDCl3): δ = 8.61 (d, J = 7.9 Hz, 1H),
7.89 (t, J = 7.9 Hz, 1H), 7.72−7.68 (m, 2H), 7.65−7.62 (m,
2H), 7.59 (d, J = 7.9 Hz, 1H), 7.49−7.33 (m, 6H), 4.85 (brꢀs,
1H), 4.22 (s, 2H), 1.48 (s, 9H); 13C NMR (125 MHz, CDCl3):
δ = 160.4, 156.7, 156.1, 153.5, 143.7, 137.4, 135.7, 135.4,
131.0, 130.2, 130.0, 129.7, 128.8, 128.7, 123.5, 85.6, 82.7,
31.3, 28.5; IR (ATRꢀCDCl3): ῡmax = 3400, 3059, 2976, 2928,
1717, 1579, 1565, 1501, 1357, 1241, 1161, 770, 696 cm−1;
HRMS (EI): m/z: [M−C4H8]+ Calcd for C28H25N5O2
463.2008; Found 407.1369.
5,6ꢀDiphenylꢀ3ꢀ(6ꢀmꢀtolylethynylꢀpyridinꢀ2ꢀyl)ꢀ[1,2,4] triaꢀ
zine (10). Prepared according to the general procedure disꢀ
cussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiphenylꢀ
[1,2,4]triazine and 1ꢀethynylꢀ3ꢀmethylꢀbenzene, Rf = 0.40,
33% EtOAc:hexanes; eluent, EtOAc/hexanes (gradient); isoꢀ
lated yield 0.0280 g, 51%; brown solid; melting point =
183.7–186.1 °C; 1H NMR (500 MHz, CDCl3): δ = 8.62 (d, J =
7.9 Hz, 1H), 7.92 (t, J = 8.0 Hz, 1H), 7.74−7.68 (m, 3H),
7.66−7.62 (m, 2H), 7.46−7.33 (m, 8H), 7.28−7.23 (m, 1H),
7.21−7.17 (m, 1H), 2.37 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ = 160.5, 156.7, 156.4, 153.5, 144.5, 138.2, 137.4,
135.7, 135.4, 132.8, 131.0, 130.2, 130.1, 130.0, 129.7, 129.4,
129.1, 128.8, 128.7, 128.4, 123.2, 122.2, 90.5, 85.6, 21.4; IR
(ATRꢀCDCl3): ῡmax = 3056, 3031, 2920, 2852, 2217, 1600,
1578, 1563, 1487, 1357, 812, 774, 690 cm−1; HRMS (EI): m/z:
[M]+ Calcd for C29H20N4 424.1688; Found 424.1677.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3ꢀ[6ꢀ(3ꢀBenzyloxyꢀpropꢀ1ꢀynyl)ꢀpyridinꢀ2ꢀyl]ꢀ5,6ꢀdiphenylꢀ
[1,2,4]triazine (15). Prepared according to the general proceꢀ
dure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀ
diphenylꢀ[1,2,4]triazine and propꢀ2ꢀynyloxymethylꢀbenzene,
Rf = 0.20, 33% EtOAc:hexanes; eluent, EtOAc/hexanes (graꢀ
dient); isolated yield 0.0359 g, 61%; brown solid; melting
5,6ꢀDiphenylꢀ3ꢀ(6ꢀpyridinꢀ2ꢀylethynylꢀpyridinꢀ2ꢀyl)ꢀ
[1,2,4]triazine (11). Prepared according to the general proceꢀ
dure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀ
diphenylꢀ[1,2,4]triazine and 2ꢀethynylpyridine, Rf = 0.10, 50%
EtOAc:hexanes; eluent, EtOAc/hexanes (gradient); isolated
yield 0.0166 g, 31%; brown solid; melting point = 227.5–
1
point = 139.0–141.6 °C; H NMR (500 MHz, CDCl3): δ =
1
231.5 °C; H NMR (500 MHz, CDCl3): δ = 8.71−8.63 (brꢀm,
8.63 (dd, J = 8.0, 0.6 Hz, 1H), 7.91 (t, J = 7.9 Hz, 1H),
7.72−7.69 (m, 2H), 7.65−7.63 (m, 3H), 7.48−7.28 (m, 11H),
4.72 (s, 2H), 4.47 (s, 2H); 13C NMR (125 MHz, CDCl3): δ =
160.4, 156.7, 156.4, 153.5, 143.7, 137.6, 137.4, 135.7, 135.4,
131.0, 130.2, 130.0, 129.7, 129.0, 128.8, 128.7, 128.6, 128.3,
2H), 7.96 (brꢀt, J = 7.8 Hz, 1H), 7.82 (d, J = 7.9 Hz, 1H),
7.76−7.67 (m, 4H), 7.65 (d, J = 7.6 Hz, 2H), 7.48−7.35 (m,
6H), 7.34−7.28 (brꢀm, 1H); 13C NMR (125 MHz, CDCl3): δ =
160.4, 156.7, 156.4, 153.6, 150.2, 143.6, 142.8, 137.5, 136.5,
135.7, 135.4, 131.0, 130.2, 130.0, 129.7, 129.66, 128.8, 128.7,
128.1, 123.9, 123.6, 88.6, 88.2; IR (ATRꢀCDCl3): ῡmax = 3057,
1580, 1564, 1507, 1390, 766, 634 cm−1; HRMS (EI): m/z:
[M]+ Calcd for C27H17N5 411.1484; Found 411.1468.
5,6ꢀDiphenylꢀ3ꢀ{6ꢀ[(triisopropylsilanyl)ꢀethynyl]ꢀpyridinꢀ2ꢀ
yl}ꢀ[1,2,4]triazine (12). Prepared according to the general
procedure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀ
diphenylꢀ[1,2,4]triazine and ethynyltriisopropylsilane, Rf =
0.72, 33% EtOAc:hexanes; eluent, EtOAc/hexanes (gradient);
isolated yield 0.0473 g, 74%; yellow solid; melting point =
137.4–142.2 °C; 1H NMR (500 MHz, CDCl3): δ = 8.61 (d, J =
7.5 Hz, 1H), 7.91 (brꢀt, J = 7.5 Hz, 1H), 7.73 (d, J = 7.7 Hz,
2H), 7.67 (d, J = 7.6 Hz, 1H), 7.47−7.34 (m, 6H), 1.23−1.11
(m, 21H); 13C NMR (125 MHz, CDCl3): δ = 160.3, 156.7,
156.4, 153.1, 144.1, 137.5, 135.6, 135.4, 131.0, 130.2, 130.0,
129.7, 128.8, 128.7, 123.6, 105.4, 94.0, 18.8, 11.4; IR (ATRꢀ
CDCl3): ῡmax = 3063, 2941, 2863, 1577, 1486, 1445, 1377,
838, 770, 698, 662 cm−1; HRMS (EI): m/z: [M]+ Calcd for
C31H34N4Si 490.2553; Found 490.2535.
128.1, 123.6, 86.3, 85.9, 72.1, 58.0; IR (ATRꢀCDCl3): ῡmax
=
3043, 2857, 2236, 1579, 1562, 1414, 1353, 1092, 734, 692,
532 cm−1; HRMS (EI): m/z: [M]+ Calcd for C30H22N4O
454.1794; Found 454.1795.
3ꢀ[6ꢀ(5,6ꢀDiphenylꢀ[1,2,4]triazinꢀ3ꢀyl)ꢀpyridinꢀ2ꢀyl]ꢀ1ꢀ
phenylꢀpropꢀ2ꢀynꢀ1ꢀol (16). Prepared according to the general
procedure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀ
diphenylꢀ[1,2,4]triazine and 1ꢀphenylꢀpropꢀ2ꢀynꢀ1ꢀol, Rf
=
0.37, 50% EtOAc:hexanes; eluent, EtOAc/hexanes (gradient);
isolated yield 0.0336 g, 59%; brown solid; melting point =
183.6–187.3 °C; 1H NMR (500 MHz, CDCl3): δ = 8.63 (d, J =
7.9 Hz, 1H), 7.91 (t, J = 7.9 Hz, 1H), 7.73−7.68 (m, 2H),
7.67−7.61 (m, 5H), 7.47−7.32 (m, 9H), 5.77 (s, 1H); 13C NMR
(125 MHz, CDCl3): δ = 160.3, 156.7, 156.4, 153.5, 143.6,
140.1, 137.4, 135.6, 135.4, 131.0, 130.2, 130.0, 129.7, 129.0,
128.8, 128.8, 128.7, 128.65, 127.0, 123.7, 89.7, 85.9, 65.1; IR
(ATRꢀCDCl3): ῡmax = 3400, 3030, 2923, 2227, 1579, 1563,
1491, 1412, 1392, 1358, 769, 739, 696 cm−1; HRMS (EI): m/z:
[M]+ Calcd for C29H20N4O 440.1637; Found 440.1651.
3ꢀ{6ꢀ[(tertꢀButylꢀdimethylꢀsilanyl)ꢀethynyl]ꢀpyridinꢀ2ꢀyl}ꢀ
5,6ꢀdiphenylꢀ[1,2,4]triazine (13). Prepared according to the
general procedure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀ
yl)ꢀ5,6ꢀdiphenylꢀ[1,2,4]triazine and tertꢀbutylethynyldimethylꢀ
silane, Rf = 0.57, 33% EtOAc:hexanes; eluent, EtOAc/hexanes
(gradient); isolated yield 0.0319 g, 55%; yellow solid; melting
3ꢀ[6ꢀ(4ꢀFluoroꢀphenylethynyl)ꢀpyridinꢀ2ꢀyl]ꢀ5,5,8,8ꢀ
tetramethylꢀ5,6,7,8ꢀtetrahydroꢀbenzo[1,2,4]triazine (17). Preꢀ
pared according to the general procedure discussed above with
3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,5,8,8ꢀtetramethylꢀ5,6,7,8ꢀtetraꢀ
hydroꢀbenzo[1,2,4]triazine and 1ꢀethynylꢀ4ꢀfluoroꢀbenzene,
RF = 0.48, 33% EtOAc:hexanes; eluent, EtOAc/hexanes (graꢀ
dient); isolated yield 0.0187 g, 37%; yellow solid; melting
1
point = 201.2–203.1 °C; H NMR (500 MHz, CDCl3): δ =
1
8.60 (dd, J = 7.9, 0.6 Hz, 1H), 7.89 (t, J = 7.9 Hz, 1H),
7.73−7.67 (m, 2H), 7.66−7.61 (m, 3H), 7.48−7.34 (m, 6H),
1.03 (s, 9H), 0.23 (s, 6H); 13C NMR (125 MHz, CDCl3): δ =
160.5, 156.6, 156.4, 153.4, 144.2, 137.2, 135.7, 135.4, 131.0,
130.2, 130.0, 129.7, 129.5, 128.8, 128.7, 123.5, 104.5, 94.6,
23.4, 16.9, −4.58; IR (ATRꢀCDCl3): ῡmax = 3052, 2926, 2854,
1576, 1566, 1409, 1357, 916, 843, 814, 772, 699, 533 cm−1;
point = 62.3–65.5 °C; H NMR (500 MHz, CDCl3): δ = 8.37
(dd, J = 7.9, 0.8 Hz, 1H), 7.85 (t, J = 7.9 Hz, 1H), 7.62 (dd, J
= 7.8, 0.8 Hz, 1H), 7.61−7.57 (m, 2H), 7.09−7.01 (m, 2H),
1.88−1.81 (m, 4H), 1.48 (s, 6H), 1.42 (s, 6H); 13C NMR (125
MHz, CDCl3): δ = 164.4, 164.0, 163.0 (J = 249.7 Hz), 160.6,
154.4, 143.9, 137.5, 134.19 (J = 8.9 Hz), 128.4, 122.9, 118.6
(J = 4.1 Hz), 115.9 (J = 21.8 Hz), 88.8, 88.6, 37.4, 36.6, 33.8,
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The Journal of Organic Chemistry
according to the general procedure discussed above with 3ꢀ(6ꢀ
33.5, 29.8, 29.3; IR (ATRꢀCDCl3): ῡmax = 3060, 2962, 2928,
1
2
3
4
5
6
7
8
2865, 2217, 1600, 1579, 1565, 1507, 1455, 1222, 835, 812,
741, 530 cm−1; HRMS (EI): m/z: [M]+ Calcd for C24H23FN4
386.1907; Found 386.1916.
bromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ[4ꢀ(3,3ꢀdimethylꢀbutyl)ꢀphenyl]ꢀ
[1,2,4]triazine and 1ꢀtertꢀbutylꢀ4ꢀethynylꢀbenzene, RF = 0.70,
33% EtOAc:hexanes; eluent, EtOAc/hexanes (gradient); isoꢀ
lated yield 0.0793 g, 96%; white solid; melting point = 192.0–
3ꢀ[6ꢀ(4ꢀMethoxyꢀphenylethynyl)ꢀpyridinꢀ2ꢀyl]ꢀ5,5,8,8ꢀ
tetramethylꢀ5,6,7,8ꢀtetrahydroꢀbenzo[1,2,4]triazine (18). Preꢀ
pared according to the general procedure discussed above with
3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,5,8,8ꢀtetramethylꢀ5,6,7,8ꢀtetraꢀ
hydroꢀbenzo[1,2,4]triazine and 1ꢀethynylꢀ4ꢀmethoxyꢀbenzene,
Rf = 0.15, 33% EtOAc:hexanes; eluent, EtOAc/hexanes (graꢀ
dient); isolated yield 0.0379 g, 73%; greenꢀyellow solid; meltꢀ
ing point = 100.3–101.6 °C; 1H NMR (500 MHz, CDCl3): δ =
8.33 (d, J = 7.9, 0.8 Hz, 1H), 7.82 (t, J = 7.7 Hz, 1H), 7.60 (d,
J = 7.9, 0.8 Hz, 1H), 7.56−7.53 (m, 2H), 6.89−6.85 (m, 2H0,
1
194.0 °C; H NMR (500 MHz, CDCl3): δ = 8.59 (dd, J = 8.0,
0.9 Hz, 1H), 7.91 (t, J = 7.9 Hz, 1H), 7.69 (dd, J = 7.9, 0.9 Hz,
1H), 7.68−7.64 (m, 2H), 7.61−7.55 (m, 4H), 7.42−7.38 (m,
2H), 7.23−7.20 (m, 2H), 7.19−7.16 (m, 2H), 2.65−2.57 (m,
4H), 1.55−1.47 (m, 4H), 1.34 (s, 9H), 0.97 (s, 9H), 0.96 (s,
9H); 13C NMR (125 MHz, CDCl3): δ = 160.2, 156.5, 156.2,
153.7, 152.5, 147.1, 145.8, 144.6, 137.2, 133.1, 132.9, 132.1,
130.2, 129.6, 128.9, 128.8, 128.7, 125.6, 123.0, 119.5, 90.4,
88.5, 46.0, 45.99, 35.0, 31.4, 31.3, 30.8, 29.49, 29.48; IR
(ATRꢀCDCl3): ῡmax = 3032, 2952, 2864, 2214, 1609, 1579,
1492, 1454, 1408, 1358, 832, 560 cm−1; HRMS (EI): m/z:
[M]+ Calcd for C44H50N4 634.4035; Found 634.4027.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3.81 (s, 3H), 1.87−1.79 (m, 4H), 1.47 (s, 6H), 1.41 (s, 6H); 13
C
NMR (125 MHz, CDCl3): δ = 164.3, 163.2, 160.7, 160.2,
154.3, 144.4, 137.0, 133.7, 128.2, 122.5, 114.5, 114.1, 90.0,
88.0, 55.4, 37.3, 36.6, 33.8, 33.4, 29.8, 29.3; IR (ATRꢀ
CDCl3): ῡmax = 3062, 2961, 2919, 2864, 2213, 1605, 1565,
1579, 1510, 1455, 1245, 1163, 831, 813, 728, 536 cm−1;
HRMS (EI): m/z: [M]+ Calcd for C25H26N4O 398.2107; Found
398.2105.
5,6ꢀBisꢀ(4ꢀbutylꢀphenyl)ꢀ3ꢀ(6ꢀcyclohexylethynylꢀpyridinꢀ2ꢀ
yl)ꢀ[1,2,4]triazine (22). Prepared according to the general
procedure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀ
bisꢀ(4ꢀbutylꢀphenyl)ꢀ[1,2,4]triazine and ethynylcyclohexane,
Rf = 0.62, 33% EtOAc:hexanes; eluent, EtOAc/hexanes (graꢀ
dient); isolated yield 0.0551 g, 80%; brown solid; melting
3ꢀ[6ꢀ(3ꢀBenzyloxyꢀpropꢀ1ꢀynyl)ꢀpyridinꢀ2ꢀyl]ꢀ5,6ꢀbisꢀ[4ꢀ
(3,3ꢀdimethylꢀbutyl)ꢀphenyl]ꢀ[1,2,4]triazine (19). Prepared
according to the general procedure discussed above with 3ꢀ(6ꢀ
bromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ[4ꢀ(3,3ꢀdimethylꢀbutyl)ꢀphenyl]ꢀ
[1,2,4]triazine and propꢀ2ꢀynyloxymethylꢀbenzene, Rf = 0.36,
33% EtOAc:hexanes; eluent, EtOAc/hexanes (gradient); isoꢀ
lated yield 0.0546 g, 67%; white solid; melting point = 174.6–
1
point = 126.0–128.0 °C; H NMR (500 MHz, CDCl3): δ =
8.53 (d, J = 7.9 Hz, 1H), 7.84 (t, J = 7.9 Hz, 1H), 7.64 (d, J =
8.2 Hz, 2H), 7.57−7.53 (m, 3H), 7.20 (d, J = 8.2 Hz, 2H), 7.16
(d, J = 8.2 Hz, 2H), 2.68−2.61 (m, 4H), 1.98−1.91 (brꢀm, 2H0,
1.83−1.75 (brꢀm, 2H), 1.66−1.58 (m, 9H), 1.42−1.30 (m, 7H),
0.94 (t J = 7.4 Hz, 3H), 0.92 (t, J = 7.4 Hz, 3H); 13C NMR
(125 MHz, CDCl3): δ = 160.3, 156.4, 155.2, 153.4, 146.3,
145.0, 144.98, 137.1, 133.2, 132.9, 130.1, 129.5, 128.8,
128.76, 128.7, 122.7, 95.9, 80.6, 35.7, 35.6, 33.4, 3.37, 32.4,
29.9, 26.0, 25.2, 22.5, 22.4, 14.1, 14.05; IR (ATRꢀCDCl3):
ῡmax = 3031, 2956, 2922, 2850, 226, 1608, 1579, 1566, 1405,
1350, 807, 732, 604 cm−1; HRMS (EI): m/z: [M]+ Calcd for
C36H40N4 528.3253; Found: 528.3253.
1
176.3 °C; H NMR (500 MHz, CDCl3): δ = 8.60 (dd, J = 8.0,
0.8 Hz, 1H), 7.89 (t, J = 7.8 Hz, 1H), 7.66−7.63 (m, 2H), 7.62
(dd, J = 7.8, 0.8 Hz, 1H0, 7.58−7.55 (m, 2H), 7.43−7.39 (m,
2H), 7.38−7.34 (m, 2H), 7.33−7.28 (m, 1H), 7.21 (d, J = 8.2
Hz, 2H0, 7.17 (d, J = 8.2 Hz, 2H), 4.72 (s, 2H), 4.47 (s, 2H),
2.64−2.56 (m, 4H), 1.54−1.46 (m, 4H), 0.97 (s, 9H), 0.95 (s,
9H); 13C NMR (125 MHz, CDCl3): δ = 160.1, 156.5, 156.2,
153.7, 147.1, 145.8, 143.7, 137.6, 137.3, 133.1, 132.8, 130.2,
129.6, 128.8, 128.77, 128.7, 128.6, 128.3, 128.0, 123.5, 86.1,
86.0, 72.1, 58.0; IR (ATRꢀCDCl3): ῡmax = 3062, 3029, 2951,
2864, 1610, 1565, 1579, 1492, 1459, 1356, 1079, 751, 700,
548 cm−1; HRMS (EI): m/z: [M−CH3]+ Calcd for C42H46N4O
622.3642; Found 607.3426.
3ꢀ(6ꢀCyclohexylethynylꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ[4ꢀ(3,3ꢀ
dimethylꢀbutyl)ꢀphenyl]ꢀ[1,2,4]triazine (23). Prepared accordꢀ
ing to the general procedure discussed above with 3ꢀ(6ꢀbromoꢀ
pyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ[4ꢀ(3,3ꢀdimethylꢀbutyl)ꢀphenyl]ꢀ
[1,2,4]triazine and ethynylꢀcyclohexane, Rf = 0.70, 33%
EtOAc:hexanes; eluent, EtOAc/hexanes (gradient); isolated
yield 0.0441 g, 58%; white solid; melting point = 214.1–216.5
°C; 1H NMR (500 MHz, CDCl3): δ = 8.52 (dd, J = 7.9, 0.8 Hz,
1H), 7.83 (t, J = 7.9 Hz, 1H), 7.66−7.62 (m, 2H), 7.58−7.53
(m, 3H), 7.22−7.19 (m, 2H), 7.18−7.15 (m, 2H), 2.68−2.54
(m, 5H), 1.98−1.91 (brꢀm, 2H), 1.83−1.75 (m, 2H), 1.63−1.55
(brꢀm, 4H), 1.54−1.46 (m, 4H), 1.39−1.32 (brꢀm, 2H), 0.97 (s,
9H), 0.96 (s, 9H); 13C NMR (125 MHz, CDCl3): δ = 160.3,
156.4, 156.1, 153.4, 147.0, 145.7, 145.0, 137.1, 133.1. 132.9,
130.2, 130.16, 129.6, 128.8, 128.6, 122.7, 95.9, 80.6, 46.0,
45.98, 32.4, 31.4, 31.3, 30.75, 30.7X (overlaps with 30.75); IR
(ATRꢀCDCl3): ῡmax = 3032, 2950, 2931, 2861, 2230, 1609,
1581, 1566, 1490, 1451, 1355, 1363, 820, 804, 731, 602 cm−1;
HRMS (EI): m/z: [M]+ Calcd for C40H48N4 584.3879; Found
584.3881.
5,6ꢀBisꢀ(4ꢀbutylꢀphenyl)ꢀ3ꢀ[6ꢀ(4ꢀfluoroꢀphenylethynyl)ꢀ
pyridinꢀ2ꢀyl]ꢀ[1,2,4]triazine (20). Prepared according to the
general procedure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀ
yl)ꢀ5,6ꢀbisꢀ(4ꢀbutylꢀphenyl)ꢀ[1,2,4]triazine and 1ꢀethynylꢀ4ꢀ
fluoroꢀbenzene, Rf = 0.55, 33% EtOAc:hexanes; eluent,
EtOAc/hexanes (gradient); isolated yield 0.0315 g, 45%; beige
1
solid; melting point = 166.0–168.0 °C; H NMR (500 MHz,
CDCl3): δ = 8.62 (dd, J = 8.0, 0.9 Hz, 1H), 7.92 (t, J = 7.9 Hz,
1H0, 7.67 (dd, J = 7.9, 0.9 Hz, 1H), 7.66−7.61 (m, 4H),
7.58−7.55 (m, 2H), 7.22−7.19 (m, 2H), 7.18−7.15 (m, 2H),
7.10−7.05 (m, 2H), 2.68−2.61 (m, 4H), 1.67−1.56 (m, 4H),
1.42−1.29 (m, 4H), 0.94 (t, J = 7.5 Hz, 3H), 0.92 (t, J = 7.5
Hz, 3H); 13C NMR (125 MHz, CDCl3): δ = 163.1 (J = 252.0
Hz), 160.2, 156.6, 156.3, 153.8, 146.4, 145.1, 144.2, 137.3,
134.3 (J = 9.0 Hz), 133.1, 132.9, 130.1, 129.6, 128.9, 128.8,
128.75, 123.3, 118.6 (J = 3.6 Hz), 115.9 (J = 22.0 Hz), 88.9,
88.7, 35.7, 35.6, 33.4, 33.36, 22.5, 22.4, 14.1, 14.0; IR (ATRꢀ
CDCl3): ῡmax = 3032, 2958, 2928, 2856, 2236, 1609, 1579,
1566, 1507, 1354, 1276, 836, 816, 607, 527 cm−1; HRMS (EI):
m/z: [M]+ Calcd for C36H33FN4 540.2689; Found 540.2689.
3ꢀ[6ꢀ(4ꢀtertꢀButylꢀphenylethynyl)ꢀpyridinꢀ2ꢀyl]ꢀ5,6ꢀbisꢀ[4ꢀ
(3,3ꢀdimethylꢀbutyl)ꢀphenyl]ꢀ[1,2,4]triazine (21). Prepared
5,6ꢀBisꢀ(4ꢀbutylꢀphenyl)ꢀ3ꢀ{6ꢀ[(triisopropylsilanyl)ꢀ
ethynyl]ꢀpyridinꢀ2ꢀyl}ꢀ[1,2,4]triazine (24). Prepared according
to the general procedure discussed above with 3ꢀ(6ꢀbromoꢀ
pyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ(4ꢀbutylꢀphenyl)ꢀ[1,2,4]triazine
and
ethynyltriisopropylsilane, Rf = 0.75, 33% EtOAc:hexanes;
eluent, EtOAc/hexanes (gradient); isolated yield 0.0509 g,
1
65%; brown oil; H NMR (500 MHz, CDCl3): δ = 8.57 (dd, J
= 8.0, 0.9 Hz, 1H), 7.86 (t, J = 7.9 Hz, 1H), 7.66−7.62 (m,
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3H), 7.58−7.55 (m, 2H), 7.20 (d, J = 7.9 Hz, 2H), 7.17 (d, J =
817, 800, 527 cm−1; HRMS (EI): m/z: [M]+ Calcd for C31H24N4
452.2001; Found 452.2015.
1
2
3
4
5
6
7
8
7.9 Hz, 2H), 2.68−2.60 (m, 4H), 1.67−1.55 (m, 4H),
1.42−1.29 (m, 4H), 1.22−1.13 (m, 21H), 0.93 (J = 7.5 Hz,
3H), 0.92 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ
= 160.2, 156.4, 156.2, 153.6, 146.4, 145.1, 144.3, 137.1,
133.1, 132.9, 130.1, 129.7, 129.5, 128.8, 128.7, 123.4, 106.0,
92.8, 35.7, 35.6, 33.4, 33.36, 22.5, 22.4, 18.8, 14.1, 14.0, 11.5;
IR (ATRꢀCDCl3): ῡmax = 3032, 2955, 2929, 2863, 2050, 1609,
1578, 1566, 1489, 1462, 1379, 882, 845, 676, 661, 561 cm−1;
HRMS (EI): m/z: [M]+ Calcd for C39H50N4Si 602.3805; Found
602.3807.
3ꢀ(6ꢀDecꢀ1ꢀynylꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiꢀpꢀtolylꢀ[1,2,4]triazine
(28). Prepared according to the general procedure discussed
above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiꢀpꢀtolylꢀ[1,2,4]
triazine and 1ꢀdecyne, Rf = 0.55, 33% EtOAc:hexanes; eluent,
EtOAc/hexanes (gradient); isolated yield 0.0556 g, 90%;
1
brown solid; melting point = 89.6–91.6 °C; H NMR (500
MHz, CDCl3): δ = 8.52 (d, J = 7.8 Hz, 1H), 7.83 (t, J = 7.8 Hz,
1H), 7.64−7.61 (m, 2H), 7.56−7.52 (m, 3H), 7.19 (d, J = 8.1
Hz, 2H), 7.15 (d, J = 8.1 Hz, 2H), 2.46 (t, J = 7.3 Hz, 2H),
2.39 (s, 3H), 2.37 (s, 3H), 1.69 (pent, J = 7.3 Hz, 2H),
1.50−1.42 (m, 2H), 1.37−1.23 (m, 8H), 0.92−0.85 (m, 3H);
13C NMR (125 MHz, CDCl3): δ = 160.3, 156.4, 156.1, 153.4,
144.9, 141.3, 140.0, 137.1, 133.0, 132.8, 130.1, 129.53,
129.48, 129.3, 128.5, 122.7, 92.2, 80.6, 32.0, 29.32, 29.28,
29.2, 28.5, 22.8, 21.63, 21.55, 19.6, 14.2; IR (ATRꢀCDCl3):
ῡmax = 3056, 3030, 2920, 2852, 2230, 1610, 1578, 1563, 1491,
1458, 1356, 820, 802, 723, 533 cm−1; HRMS (EI): m/z: [M]+
Calcd for C30H30N4 446.2470; Found: 446.2451.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3ꢀ{6ꢀ[(tertꢀButylꢀdimethylꢀsilanyl)ꢀethynyl]ꢀpyridinꢀ2ꢀyl}ꢀ
5,6ꢀbisꢀ[4ꢀ(3,3ꢀdimethylꢀbutyl)ꢀphenyl]ꢀ[1,2,4]triazine (25).
Prepared according to the general procedure discussed above
with
3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ[4ꢀ(3,3’ꢀdimethylꢀ
butyl)ꢀphenyl]ꢀ[1,2,4]triazine and tertꢀbutylꢀethynyldimethylꢀ
silane, Rf = 0.48, 33% EtOAc:hexanes; eluent, EtOAc/hexanes
(gradient); isolated yield 0.0443 g, 55%; white solid; melting
1
point = 192.0–194.0 °C; H NMR (500 MHz, CDCl3): δ =
8.57 (dd, J = 7.9, 0.8 Hz, 1H), 7.86 (t, J = 7.9 Hz, 1H0,
7.66−7.63 (m, 2H), 7.62 (dd, J = 7.9, 0.9 Hz, 1H), 7.58−7.54
(m, 2H), 7.22−7.19 (m, 2H), 7.18−7.15 (m, 2H), 2.64−2.55
(m, 4H), 1.53−1.47 (m, 4H), 1.03 (s, 9H), 0.97 (s, 9H), 0.95 (s,
9H0, 0.22 (s, 6H); 13C NMR (125 MHz, CDCl3): δ = 160.2,
156.4, 155.2, 153.6, 153.6X (overlaps with 153.6), 147.1,
145.8, 144.1, 137.1, 133.1, 132.8, 130.2, 129.6, 129.2, 128.8,
128.7, 123.4, 104.6, 94.4, 46.0, 45.97, 31.4, 31.3, 30.75,
30.7X (overlaps with 30.75), 29.48, 29.47, 26.3, 16.9, −4.6; IR
(ATRꢀCDCl3): ῡmax = 2953, 2900, 2861, 1609, 1578, 1567,
1493, 1468, 1351, 1248, 917, 851, 824, 781 cm−1; HRMS (EI):
m/z: [M]+ Calcd for C40H52N4Si 616.3961; Found 616.3965.
5,6ꢀBisꢀ(4ꢀbutylꢀphenyl)ꢀ3ꢀ(6ꢀdecꢀ1ꢀynylꢀpyridinꢀ2ꢀyl)ꢀ
5,6ꢀBisꢀ(4ꢀfluoroꢀphenyl)ꢀ3ꢀ(6ꢀphenylethynylꢀpyridinꢀ2ꢀyl)ꢀ
[1,2,4]triazine (29). Prepared according to the general proceꢀ
dure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ
(4ꢀfluoroꢀphenyl)ꢀ[1,2,4]triazine and ethynylbenzene, Rf
=
0.39, 33% EtOAc:hexanes; eluent, EtOAc/hexanes (gradient);
isolated yield 0.041 g, 79%; brown solid; melting point =
1
156.9–159.8 °C; H NMR (500 MHz, CDCl3): δ = 8.60 (dd, J
= 8.0, 0.8 Hz, 1H), 7.93 (t, J = 7.8 Hz, 1H), 7.75−7.68 (m,
3H), 7.66−7.61 (m, 4H), 7.41−7.34 (m, 3H), 7.14−7.03 (m,
4H); 13C NMR (125 MHz, CDCl3): δ = 165.3 (J = 76.8 Hz),
163.2 (J = 72.9 Hz), 160.5, 155.5, 155.1, 153.2, 144.4, 137.4,
132.4 (J = 9.0 Hz), 132.2, 131.6 (J = 9.0 Hz), 131.5 (J = 2.7
Hz), 131.3 (J = 3.5 Hz), 129.20, 129.15, 128.5, 123.3, 116.2 (J
= 11.7 Hz), 116.0 (J = 11.9 Hz), 90.2, 88.8; IR (ATRꢀCDCl3):
ῡmax = 3063, 2237, 1601, 1579, 1564, 1492, 1357, 1229, 1160,
911, 841, 725, 686, 558, 536, 517 cm−1; HRMS (EI): m/z:
[M]+ Calcd for C28H16F2N4 446.1343; Found 446.1358.
[1,2,4]triazine (26). Prepared according to the general proceꢀ
dure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ
(4ꢀbutylꢀphenyl)ꢀ[1,2,4]triazine and 1ꢀdecyne, Rf = 0.75, 33%
EtOAc:hexanes; eluent, EtOAc/hexanes (gradient); isolated
1
yield 0.0486 g, 67%; dark brown oil; H NMR (500 MHz,
CDCl3): δ = 8.55 (d, J = 7.9 Hz, 1H), 7.87 (t, J = 7.9 Hz, 1H),
7.66 (d, J = 8.2 Hz, 2H0, 7.58−7.54 (m, 2H), 7.22−7.18 (m,
2H), 7.17−7.14 (m, 2H), 2.68−2.60 (m, 4H), 2.47 (t, J = 7.2
Hz, 2H), 1.69−1.56 (m, 6H), 1.50−1.43 (m, 2H), 1.41−1.24
(m, 12H), 0.94 (t, J = 7.5 Hz, 3H), 0.92 (t, J = 7.5 Hz, 3H),
0.89 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ =
160.0, 156.5, 156.2, 153.2, 146.3, 145.1, 144.6, 137.5, 133.1,
132.9, 130.2, 129.6, 128.8, 128.7, 122.8, 93.1, 80.3, 35.7,
35.6, 33.43, 33.4, 32.0, 29.33, 29.3, 29.2, 28.4, 22.8, 22.5,
22.4, 19.7, 14.2; IR (ATRꢀCDCl3): ῡmax = 3058, 3031, 2954,
2926, 2855, 2228, 1609, 1580, 1565, 1455, 1489, 1379, 1357,
829, 806, 737, 549 cm−1; HRMS (EI): m/z: [M]+ Calcd for
C38H46N4 558.3722; Found 558.3722.
5,6ꢀBisꢀ(4ꢀfluoroꢀphenyl)ꢀ3ꢀ[6ꢀ(4ꢀfluoroꢀphenylethynyl)ꢀ
pyridinꢀ2ꢀyl]ꢀ[1,2,4]triazine (30). Prepared according to the
general procedure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀ
yl)ꢀ5,6ꢀbisꢀ(4ꢀfluoroꢀphenyl)ꢀ[1,2,4]triazine and 1ꢀethynylꢀ4ꢀ
fluoroꢀbenzene, Rf = 0.48, 33% EtOAc:hexanes; eluent,
EtOAc/hexanes (gradient); isolated yield 0.0443 g, 73%; beige
1
solid; melting point = 180.6–183.5 °C; H NMR (500 MHz,
C6D6): δ = 8.61 (d, J = 7.9 Hz, 1H), 7.39−7.34 (m, 2H),
7.31−7.29 (m, 3H), 7.21−7.12 (m, 3H), 6.70−6.64 (m, 2H),
6.62−6.52 (m, 4H); 13C NMR (125 MHz, C6D6): δ = 165.3 (J
= 269.2 Hz), 163.9 (J = 356.1 Hz), 162.7 (J = 378.5 Hz),
161.1, 155.3, 154.7, 154.2, 144.6, 137.0, 134.4 (J = 33.4 Hz),
132.8 (J = 34.5 Hz), 132.0 (J = 34.3 Hz), 128.7, 128.4, 128.2,
123.5, 118.8 (J = 13.6 Hz), 116.0 (J = 11.1 Hz), 115.8 (J =
10.0 Hz), 115.6, 89.5, 89.1; IR (ATRꢀCDCl3): ῡmax = 3068,
2236, 1601, 1578, 1563, 1505, 1358, 1225, 1159, 832, 815,
536, 526 cm−1; HRMS (EI): m/z: [M]+ Calcd for C28H15F3N4
464.1249; Found 464.1235.
5,6ꢀBisꢀ(4ꢀfluoroꢀphenyl)ꢀ3ꢀ[6ꢀ(4ꢀmethoxyꢀphenylꢀethynyl)ꢀ
pyridinꢀ2ꢀyl]ꢀ[1,2,4]triazine (31). Prepared according to the
general procedure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀ
yl)ꢀ5,6ꢀbisꢀ(4ꢀfluoroꢀphenyl)ꢀ[1,2,4]triazine and 1ꢀethynylꢀ4ꢀ
methoxybenzene, Rf = 0.42, 33% EtOAc:hexanes; neutral
alumina; eluent, EtOAc/hexanes (gradient); isolated yield
0.0320 g, 52%; yellow solid; melting point = 185.1–186.5 °C;
1H NMR (500 MHz, CDCl3): δ = 8.59 (d, J = 8.0 Hz, 1H),
7.92 (t, J = 7.8 Hz, 1H), 7.77−7.72 (m, 2H), 7.70 (d, J = 7.8
5,6ꢀDiꢀpꢀtolylꢀ3ꢀ(6ꢀpꢀtolylethynylꢀpyridinꢀ2ꢀyl)ꢀ[1,2,4] triaꢀ
zine (27). Prepared according to the general procedure disꢀ
cussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀdiꢀpꢀtolylꢀ
[1,2,4]triazine and 1ꢀethynylꢀ4ꢀmethylbenzene, Rf = 0.60, 33%
EtOAc:hexanes; eluent, EtOAc/hexanes (gradient); isolated
yield 0.0338 g, 62%; yellow solid; melting point = 184.8–
1
186.2 °C; H NMR (500 MHz, CDCl3): δ = 8.59 (d, J = 7.9
Hz, 1H), 7.91 (t, J = 7.9 Hz, 1H), 7.69 (d, J = 7.5 Hz, 1H),
7.64 (d, J = 7.9 Hz, 2H), 7.57−7.52 (m, 4H), 7.23−7.13 (m,
6H), 2.40 (s, 3H), 2.38 (s, 6H); 13C NMR (125 MHz, CDCl3):
δ = 160.3, 156.5, 153.7, 144.5, 151.4, 140.1, 139.4, 137.3,
133.0, 132.8, 132.2, 130.2, 129.6, 129.5, 129.4, 129.3, 128.8,
123.1, 119.4, 90.4, 88.5, 21.8, 21.7, 21.6; IR (ATRꢀCDCl3):
ῡmax = 3031, 2920, 2856, 2230, 1608, 1578, 1565, 1488, 1357,
8
ACS Paragon Plus Environment

Page 9 of 11
The Journal of Organic Chemistry
Hz, 1H), 7.67−7.61 (m, 2H), 7.60−7.57 (m, 2H), 7.15−7.06
= 3068, 2938, 2225, 1599, 1577, 1562, 1508, 1354, 1227,
(m, 4H), 6.93−6.89 (m, 2H), 3.86 (s, 3H); 13C NMR (125
MHz, CDCl3): δ = 165.3 (J = 76.4 Hz), 163.3 (J = 73.6 Hz),
160.6, 160.5, 133.9, 132.5 (J = 8.9 Hz), 131.7 (J = 8.9 Hz),
131.6 (J = 3.1 Hz), 131.4 (J = 3.3 Hz), 129.0, 123.0, 116.3 (J
= 48.8 Hz), 116.1 (J = 48.6 Hz), 114.4, 114.3, 90.7, 87.9, 55.5;
IR (ATRꢀCDCl3): ῡmax = 3050, 2209, 1601, 1577, 1559, 1510,
1487, 1354, 1225, 1155, 834, 829, 810, 552, 547, 527 cm−1;
HRMS (EI): m/z: [M]+ Calcd for C29H18F2N4O 476.1449;
Found 476.1444.
1036, 839, 811, 708 cm−1; HRMS (EI): m/z: [M]+ Calcd for
C30H21FN4O2 488.1649; Found 488.1640.
1
2
3
4
5
6
7
8
5,6ꢀBisꢀ(3ꢀmethoxyꢀphenyl)ꢀ3ꢀ[6ꢀ(4ꢀmethoxyꢀphenylꢀ
ethynyl)ꢀpyridinꢀ2ꢀyl]ꢀ[1,2,4]triazine (35). Prepared according
to the general procedure discussed above with 3ꢀ(6ꢀbromoꢀ
pyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ(3ꢀmethoxyꢀphenyl)ꢀ[1,2,4]triazine and
1ꢀethynylꢀ4ꢀmethoxyꢀbenzene, Rf = 0.10, 33% EtOAc:hexꢀ
anes; eluent, EtOAc/hexanes (gradient); isolated yield 0.0375
1
g, 58%; brown solid; melting point = 145.0–147.0 °C; H
9
3ꢀ[6ꢀ(4ꢀFluoroꢀphenylethynyl)ꢀpyridinꢀ2ꢀyl]ꢀ5,6ꢀbisꢀ(4ꢀ
methoxyꢀphenyl)ꢀ[1,2,4]triazine (32). Prepared according to
the general procedure discussed above with 3ꢀ(6ꢀbromoꢀ
pyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ(4ꢀmethoxyꢀphenyl)ꢀ[1,2,4]triazine and
1ꢀethynylꢀ4ꢀfluoroꢀbenzene, Rf = 0.10, 33% EtOAc:hexanes;
eluent, EtOAc/hexanes (gradient); isolated yield 0.0500 g,
NMR (500 MHz, CDCl3): δ = 8.59 (d, J = 7.9 Hz, 1H), 7.91 (t,
J = 7.9 Hz, 1H), 7.68 (d, J = 7.9 Hz, 1H), 7.61−7.55 (m, 3H),
7.31−7.23 (m, 5H), 7.14 (d, J = 7.7 Hz, 1H), 7.01−6.96 (m,
2H), 6.92−6.87 (m, 2H), 3.84 (s, 3H), 3.77 (s, 3H), 3.73 (s,
3H); 13C NMR (125 MHz, CDCl3): δ = 160.6, 160.4, 159.9,
159.8, 156.5, 156.3, 153.4, 144.7, 137.3, 137.0, 136.7, 133.9,
129.8, 129.75, 128.9, 123.0, 122.7, 122.3, 117.3, 116.3, 115.0,
114.5, 114.5X (overlaps with 114.5), 114.2, 90.5, 88.0, 55.50,
55.49, 55.48,; IR (ATRꢀCDCl3): ῡmax = 3068, 2938, 2834,
2220, 1603, 1576, 1563, 1510, 1352, 1228, 811, 805, 537,
cm−1; HRMS (EI): m/z: [M]+ Calcd for C31H24N4O3 500.1848;
Found: 500.1832.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
79%; brown solid; melting point = 173.6–178.0 °C; H NMR
(500 MHz, CDCl3): δ = 8.60 (dd, J = 7.9, 0.5 Hz, 1H), 7.92 (t,
J = 7.9 Hz, 1H), 7.77−7.73 (m, 2H), 7.68 (dd, J = 7.9, 0.5 Hz,
1H), 7.66−7.61 (m, 4H), 7.10−7.05 (m, 2H), 6.95−6.91 (m,
2H), 6.90−6.87 (m, 2H), 3.86 (s, 3H), 3.85 (s, 3H); 13C NMR
(125 MHz, CDCl3): δ = 164.1, 162.1, 161.6 (J = 121.0 Hz),
159.9, 155.9, 155.5, 153.8, 144.2, 137.3, 134.3, 134.2, 131.9,
131.1, 128.8, 128.1 (J = 2.9 Hz), 123.2, 118.7 (J = 3.6 Hz),
115.9 (J = 21.8 Hz), 114.4, 114.2, 88.9, 88.8, 55.54, 55.50; IR
(ATRꢀCDCl3): ῡmax = 3070, 2235, 1607, 1577, 1566, 1508,
1490, 1355, 1252, 1177, 832, 527 cm−1; HRMS (EI): m/z:
[M]+ Calcd for C30H21FN4O2 488.1649; Found 488.1635.
5,6ꢀBisꢀ(4ꢀfluoroꢀphenyl)ꢀ3ꢀ(6ꢀoctꢀ1ꢀynylꢀpyridinꢀ2ꢀyl)ꢀ
1ꢀ(6ꢀpꢀTolylethynylꢀpyridinꢀ2ꢀyl)ꢀethanone (36). Prepared
according to the general procedure discussed above with subꢀ
strate 1ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀethanone and 1ꢀethynylꢀ4ꢀ
methylbenzene, Rf = 0.69, 33% EtOAc:hexanes; eluent,
EtOAc/hexanes (gradient); isolated yield 0.0495 g, 84%; beige
1
solid; melting point = 111.3–112.4 °C; H NMR (500 MHz,
CDCl3): δ = 7.96 (brꢀd, J = 7.6 Hz, 1H), 7.81 (brꢀt, J = 7.6 Hz,
1H), 7.67 (brꢀd, J = 7.6 Hz, 1H), 7.52 (d, J = 7.8 Hz, 2H), 7.19
(d, J = 7.8 Hz, 2H), 2.77 (s, 3H), 2.39 (s, 3H); 13C NMR (125
MHz, CDCl3): δ = 200.0, 154.0, 143.2, 139.7, 137.1, 132.2,
130.6, 129.4, 120.6, 119.0, 90.3, 87.8, 26.0, 21.8; IR (ATRꢀ
CDCl3): ῡmax = 2923, 2206, 1700, 1574, 1561, 1358, 815, 603
cm−1; HRMS (EI): m/z: [M]+ Calcd for C16H13NO 235.0997;
Found: 235.0991.
[1,2,4]triazine (33). Prepared according to the general proceꢀ
dure discussed above with 3ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ
(4ꢀfluoroꢀphenyl)ꢀ[1,2,4]triazine and 1ꢀoctyne, Rf = 0.38, 33%
EtOAc:hexanes; eluent, EtOAc/hexanes (gradient); isolated
1
yield 0.0460 g, 78%; brown amorphous; H NMR (500 MHz,
CDCl3): δ = 8.54 (d, J = 7.9 Hz, 1H), 7.82 (d, J = 7.9 Hz, 1H),
7.74−7.71 (m, 2H), 7.65−7.61 (m, 2H), 7.56 (d, J = 7.9 Hz,
1H), 7.14−7.09 (m, 2H), 7.08−7.05 (m, 2H), 2.47 (t, J = 7.2
Hz, 2H), 1.66 (pent, J = 7.4 Hz, 2H), 1.52−1.44 (m, 2H),
1.38−1.29 (m, 4H), 0.91 (t, J = 6.8 Hz, 3H); 13C NMR (125
MHz, CDCl3): δ = 165.3 (J = 75.7 Hz), 163.3 (J = 73.5 Hz),
160.6, 155.4, 155.2, 153.0, 145.0, 137.3, 132.4 (J = 9.1 Hz),
131.7 (J = 9.1 Hz), 131.6 (J = 2.7 Hz), 131.4 (J = 3.8 Hz),
128.9, 122.8, 116.2 (J = 15.2 Hz), 116.1 (J = 14.2 Hz), 116.0,
92.5, 80.5, 31.5, 28.9, 28.4, 22.7, 19.6, 14.2; IR (ATRꢀ
CDCl3): ῡmax = 3066, 2958, 2924, 2856, 2227, 1597, 1580,
1509, 1491, 1356, 1225, 1157, 861, 844, 813, 805, 541 cm−1;
HRMS (EI): m/z: [M]+ Calcd for C28H24F2N4 454.1969; Found
454.1954.
6ꢀpꢀTolylethynylꢀpyridineꢀ2ꢀcarbaldehyde (37). Prepared
according to the general procedure discussed above with 6ꢀ
bromoꢀpyridineꢀ2ꢀcarbaldehyde and 1ꢀethynylꢀ4ꢀmethyl benꢀ
zene, Rf = 0.68, 33% EtOAc:hexanes; eluent, EtOAc/hexanes
(gradient); isolated yield 0.0333 g, 56%; brown solid; melting
1
point = 116.7–120.3 °C; H NMR (500 MHz, CDCl3): δ =
10.10 (s, 1H), 7.91−7.85 (m, 2H), 7.73 (dd, J = 7.5, 1.5 Hz,
1H), 7.54−7.51 (m, 2H), 7.19 (d, J = 7.8 Hz, 2H), 2.39 (s, 3H);
13C NMR (125 MHz, CDCl3): δ = 193.2, 153.1, 144.5, 140.0,
137.5, 132.3, 131.3, 129.4, 120.3, 118.7, 91.3, 87.2, 21.8; IR
(ATRꢀCDCl3): ῡmax = 3064, 2833, 2210, 1712, 1701, 1577,
1510, 1212, 819, 801, 529 cm−1; HRMS (EI): m/z: [M]+ Calcd
for C15H11NO 221.0841; Found 221.0834.
3ꢀ[6ꢀ(4ꢀFluoroꢀphenylethynyl)ꢀpyridinꢀ2ꢀyl]ꢀ5,6ꢀbisꢀ(3ꢀ
methoxyꢀphenyl)ꢀ[1,2,4]triazine (34). Prepared according to
the general procedure discussed above with 3ꢀ(6ꢀbromoꢀ
pyridinꢀ2ꢀyl)ꢀ5,6ꢀbisꢀ(3ꢀmethoxyꢀphenyl)ꢀ[1,2,4]triazine and
1ꢀethynylꢀ4ꢀfluoroꢀbenzene, RF = 0.18, 33% EtOAc:hexanes;
eluent, EtOAc/hexanes (gradient); isolated yield 0.0352 g,
6ꢀpꢀTolylethynylꢀpyridineꢀ2ꢀcarbonitrile (38). Prepared acꢀ
cording to the general procedure discussed above with 6ꢀ
bromoꢀpyridineꢀ2ꢀcarbonitrile
and
1ꢀethynylꢀ4ꢀmethylꢀ
benzene, Rf 0.50, 33% EtOAc:hexanes; eluent,
=
EtOAc/hexanes (gradient); isolated yield 0.0342 g, 58%;
1
1
55%; brown solid; melting point = 189.0–192.7 °C; H NMR
brown solid; melting point = 155.4–158.3 °C; H NMR (500
(500 MHz, CDCl3): δ = 8.65 (d, J = 7.7 Hz, 1H), 7.94 (brꢀt, J
= 7.7 Hz, 1H), 7.72−7.68 (m, 1H), 7.63 (dd, J = 8.5, 5.4 Hz,
2H), 7.31−7.24 (m, 5H), 7.15 (d, J = 7.4 Hz, 1H), 7.08 (brꢀt, J
= 8.5 Hz, 2H), 7.01−6.97 (m, 2H), 3.77 (s, 3H), 3.73 (s, 3H);
13C NMR (125 MHz, CDCl3): δ = 163.0 (J = 250.0 Hz), 160.5,
159.9, 159.8, 156.6, 156.3, 153.5, 144.2, 137.5, 136.9, 136.6,
134.3, 134.26, 129.8 (J = 2.8 Hz), 129.0, 123.4, 122.7, 122.3,
118.6 (J = 3.6 Hz), 117.2, 116.3, 115.9 (J = 22.3 Hz), 115.9,
115.1, 114.6, 89.2, 88.6, 55.54, 55.50; IR (ATRꢀCDCl3): ῡmax
MHz, CDCl3): δ = 7.81 (t, J = 7.8 Hz, 1H), 7.69 (dd, J = 8.1,
0.9 Hz, 1H), 7.62 (dd, J = 7.8, 0.9 Hz, 1H), 7.51 (d, J = 8.1
Hz, 2H), 7.19 (d, J = 8.1 Hz, 2H), 2.39 (s, 3H); 13C NMR (125
MHz, CDCl3): δ = 145.5, 140.3, 137.4, 134.3, 132.3, 130.2,
128.5, 120.1, 118.3, 116.8, 92.4, 86.7, 21.8; IR (ATRꢀCDCl3):
ῡmax = 3051, 2205, 1578, 1550, 1449, 988, 817, 534 cm−1;
HRMS (EI): m/z: [M]+ Calcd for C15H10N2 218.0844; Found
218.0852.
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Page 10 of 11
2ꢀ(4ꢀBromoꢀphenylethynyl)ꢀ6ꢀmethylꢀpyridine (39). Preꢀ
pared according to the general procedure discussed above with
2ꢀbromoꢀpyridineꢀ3ꢀcarbaldehyde and 1ꢀbromoꢀ4ꢀethynylꢀ
ASSOCIATED CONTENT
1
2
3
4
5
6
7
8
Supporting Information
benzene, Rf
=
0.63, 33% EtOAc:hexanes; eluent,
The Supporting Information is available free of charge on
the ACS Publications website at DOI:
EtOAc/hexanes (gradient); isolated yield 0.0448 g, 57%; white
1
solid; melting point = 107.9–111.4 °C; H NMR (500 MHz,
Copies of 1H and 13C NMR spectra as well as purification
chromatograms for all compounds. (PDF)
CDCl3): δ = 7.58 (t, J = 8.1 Hz, 1H), 7.52−7.43 (m, 4H), 7.36
(d, J = 7.8 Hz, 1H), 7.13 (d, J = 7.8 Hz, 1H), 2.60 (s, 3H); 13
C
NMR (125 MHz, CDCl3): δ = 159.3, 142.5, 136.6, 133.6,
131.8, 124.6, 123.4, 123.0, 121.5, 90.0, 87.8, 24.8; IR (ATRꢀ
CDCl3): ῡmax = 2920, 1576, 1563, 1485, 1444, 1394, 1009,
827, 816, 792, 521 cm−1; HRMS (EI): m/z: [M]+ Calcd for
C14H10BrN 270.9997; Found 270.9987.
AUTHOR INFORMATION
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Corresponding Author
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* Email: jcarrick@tntech.edu
Notes
2ꢀpꢀTolylethynylꢀpyridineꢀ3ꢀcarbaldehyde (40). Prepared
according to the general procedure discussed above with 2ꢀ
The authors declare no competing interest.
bromoꢀpyridineꢀ3ꢀcarbaldehyde
and
1ꢀethynylꢀ4ꢀ
ACKNOWLEDGMENTS
methylbenzene, Rf = 0.43, 33% EtOAc:hexanes; eluent,
EtOAc/hexanes (gradient); isolated yield 0.0240 g, 40%;
Financial support for this work was provided by an award
from the U.S. Department of Energy, Basic Energy Sciences,
Separations Program Award: DEꢀSC0018033. An award from
the National Science Foundation Major Research Instrumentaꢀ
tion Program (1531870) is gratefully acknowledged for the
acquisition of the University’s 500 MHz multinuclear NMR
spectrometer with broadꢀband N2 cryoprobe. The authors
would like to thank Dr. Qiaoli Liang, The University of Alaꢀ
bama, for acquisition of HRMS data. Jacob W. Cleveland and
Ai Lin Chin are acknowledged for the preparation of the reqꢀ
uisite scaffolds leading to the production of 27−31 and 33.
1
brown solid; melting point = 92.5–94.9 °C; H NMR (500
MHz, CDCl3): δ = 10.65 (s, 1H), 8.80 (dd, J = 4.7, 1.8 Hz,
1H), 8.19 (dd, J = 8.0, 1.8 Hz, 1H), 7.53 (d, J = 8.1 Hz, 2H),
7.38 (dd, J = 8.0, 4.7 Hz, 1H0, 7.20 (d, J = 8.1 Hz, 2H), 2.39
(s, 3H); 13C NMR (125 MHz, CDCl3): δ = 191.0, 154.6, 146.4,
140.5, 134.9, 132.2, 131.8, 129.5, 123.1, 118.3, 96.7, 84.4,
21.8; IR (ATRꢀCDCl3): ῡmax = 3040, 2214, 1689, 1574, 1558,
1426, 1256, 810, 790, 758, 516 cm−1; HRMS (EI): m/z: [M]+
Calcd for C15H11NO 221.0841; Found 221.0840.
1ꢀ[6ꢀ(4ꢀBromoꢀphenylethynyl)ꢀpyridinꢀ2ꢀyl]ꢀethanone (41).
Prepared according to the general procedure discussed above
with 1ꢀ(6ꢀbromoꢀpyridinꢀ2ꢀyl)ꢀethanone and 1ꢀbromoꢀ4ꢀ
ethynylꢀbenzene: Rf = 0.70, 33% EtOAc:hexanes; neutral
alumina; eluent, EtOAc/hexanes (gradient); isolated yield
0.0300 g, 40%; white solid; melting point = 112.4–114.3 °C;
1H NMR (500 MHz, CDCl3): δ = 7.99 (d, J = 7.8 Hz, 1H),
7.83 (t, J = 7.8 Hz, 1H), 7.68 (d, J = 7.8 Hz, 1H), 7.55−7.51
(m, 2H), 7.50−7.45 (m, 2H), 2.77 (s, 3H); 13C NMR (125
MHz, CDCl3): δ = 199.8, 154.0, 142.7, 137.2, 133.6, 131.9,
130.7, 123.8, 121.1, 120.9, 89.3, 88.7, 26.0; IR (ATRꢀCDCl3):
ῡmax = 2206, 1694, 1572, 1557, 1482, 1445, 823, 812, 608,
514, cm−1; HRMS (EI): m/z: [M]+ Calcd for C15H10BrNO
298.9946; Found 298.9941.
3ꢀ{6ꢀ[4ꢀ(3,3ꢀDimethylꢀbutyl)ꢀphenylethynyl]ꢀpyridinꢀ2ꢀyl}ꢀ
5,6ꢀdiphenylꢀ[1,2,4]triazine (42). An 8 mL reaction vial
equipped with a magnetic stirring bar at ambient temperature
was charged 9 (0.050 g, 0.102 mmol, 1.00 equiv), Pd(OAc)2
(0.001 g, 0.005 mmol, 1.00 equiv), RuPhos (0.005 g, 0.001
mmol, 1.00 equiv), and Cs2CO3 (0.098 g, 0.300 mmol, 3.00
equiv). The mixture was slurried in toluene:H2O (4:1) (0.2 M)
and heated to 115 °C for 16 h. Subsequent the crude material
was absorbed on normal phase silica gel and purified using
automated flash column chromatography to afford the title
compound (0.0134 g, 27%): Rf = 0.45, 33% EtOAc:hexanes;
eluent, EtOAc/hexanes (gradient); yellow solid; melting point
= 199.0–200.4 °C; 1H NMR (500 MHz, CDCl3): δ = 8.61 (dd,
J = 8.1, 0.9 Hz, 1H), 7.92 (t, J = 7.8 Hz, 1H), 7.74−7.69 (m,
3H), 7.66−7.63 (m, 2H), 7.57−7.54 (m, 2H), 7.48−7.35 (m,
6H), 7.21−7.18 (m, 2H), 2.62−2.57 (m, 2H), 1.54−1.48 (m,
2H), 0.97 (s, 9H); 13C NMR (125 MHz, CDCl3): δ = 160.6,
156.6, 156.5, 153.5, 145.1, 144.6, 137.3, 135.7, 135.4, 132.3,
130.9, 130.2, 129.9, 129.7, 129.0, 128.8, 128.7, 128.6, 123.1,
119.5, 90.6, 88.4, 46.2, 31.5, 30.7, 29.5; IR (ATRꢀCDCl3):
ῡmax = 3057, 2952, 2869, 2204, 1577, 1564, 1492, 1358, 812,
771, 693 cm−1; HRMS (EI): m/z: [M]+ Calcd for C34H30N4
494.2470; Found 494.2485.
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