PhI(OCOCF3)2-mediated intramolecular oxidative N-N bond formation: Metal-free synthesis of 1,2,4-triazolo[1,5-a]pyridines

Article abstract of DOI:10.1021/jo500298j

The biologically important 1,2,4-triazolo[1,5-a]pyridines were readily synthesized from N-(pyridin-2-yl)benzimidamides via phenyliodine bis(trifluoroacetate)-mediated intramolecular annulation. This novel strategy allows for the convenient construction of a 1,2,4-triazolo[1,5-a]pyridine skeleton through direct metal-free oxidative N-N bond formation, featuring a short reaction time and high reaction yields.

Full text of DOI:10.1021/jo500298j

Note
pubs.acs.org/joc
PhI(OCOCF3)2‑Mediated Intramolecular Oxidative N−N Bond
Formation: Metal-Free Synthesis of 1,2,4-Triazolo[1,5‑a]pyridines
Zisheng Zheng,† Shuangyu Ma,† Linlin Tang,† Daisy Zhang-Negrerie,† Yunfei Du,*,†,‡ and Kang Zhao*,†
†Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin
University, Tianjin 300072, China
‡Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China
S
* Supporting Information
ABSTRACT: The biologically important 1,2,4-triazolo[1,5-a]pyridines
were readily synthesized from N-(pyridin-2-yl)benzimidamides via phenyl-
iodine bis(trifluoroacetate)-mediated intramolecular annulation. This novel
strategy allows for the convenient construction of a 1,2,4-triazolo[1,5-
a]pyridine skeleton through direct metal-free oxidative N−N bond
formation, featuring a short reaction time and high reaction yields.
n the past two decades, hypervalent iodine reagents have
emerged as a class of non-metal oxidants with superb
Scheme 1. Previously Reported Construction of
Heterocycles through I(III)-Mediated N−N Bond
Formation
I
oxidizing power and environmental benignity.1 In particular,
hypervalent iodine(III) reagents such as phenyliodine(III)
diacetate (PIDA) and phenyliodine(III) bis(trifluoroacetate)
(PIFA) have found wide applications in the construction of
various heterocyclic compounds.2 Among these methods,
intramolecular carbon−heteroatom3−5 and carbon−carbon
bond formation6 strategies have been intensively investigated.
However, a careful literature survey indicated that there are
only a few reports describing the synthesis of heterocycles
through the heteroatom−heteroatom bond forming ap-
proach,7−9 although such a strategy may comply well with
the atom economy principle and provides the most
straightforward access to the desired heterocyclic compounds.
In particular, the formation of heterocycles through the I(III)-
mediated N−N bond forming reactions was very limited, as
shown in Scheme 1.9 In 1996, Kotali et al. reported a PIDA-
mediated oxidative cyclization of o-aminoaryl ketone acylhy-
drazones to afford aminoindazoles, in which the two hydrogens
on the aryl amine moiety were dehydrogenatively removed.9a
Hirota and co-workers applied the same oxidative cyclization
strategy to the construction of pyrazolo[3,4-d]pyrimidines.7a In
herein disclose a convenient assemblage of the biologically
important 1,2,4-triazolo[1,5-a]pyridine skeleton10,11 through
PIFA-mediated, intramolecular oxidative N−N bond coupling
in N-(pyridin-2-yl)benzimidamide compounds, many advanta-
geous features of which identify with those of “click
chemistry”.12,13
Today, many synthetic routes to 1,2,4-triazolo[1,5-a]-
pyridines have been explored.11 Oxidative cyclization of
amidine derivatives with various oxidants, such as NaClO/
base,11a Pb(OAc)4,11b or MnO2,11h was the most straightfor-
ward strategy. However, some disadvantages of the existing
methods, including low yields and scope limitations,
encouraged us to develop methods that proceed at ambient
́
2006, Tellitu, Dominguez, and their co-workers described the
construction of N,N′-disubstituted indazolones from methyl
anthranilates through PIFA-mediated N−N bond formation.9b,c
During the process, the two hydrogens on the two respective N
atoms were oxidatively removed. Subsequently, Malamidou-
Xenikaki applied a similar strategy to the synthesis of
denocarboxamides.9d Dong et al. also reported a synthesis of
spiro-fused pyrrazolin-5-one N-oxides from 1-carbamoyl-1-
oximylcycloalkanes employing a PIFA-mediated N−N bond
forming approach.9e The hydrogen on the oxime moiety and
the hydrogen on the amide moiety can be considered to be
oxidatively eliminated during the transformation. Continuing
our research into constructing heterocyclic compounds through
hypervalent iodine-mediated reactions, we have established and
Received: February 10, 2014
Published: April 18, 2014
© 2014 American Chemical Society
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Note
a
temperature efficiently devoid of transition metal catalysts or
metal-containing oxidants.
Table 1. Optimization of Reaction Conditions
In 2012, Zhu et al. reported that the N-aryl amidines A could
smoothly undergo direct oxidative C−N bond formation to
afford 2-substituted benzimidazoles B in satisfactory to high
yields (Scheme 2, eq 1).3b Inspired by their work as well as
b
entry
1
oxidant (equiv)
solvent
conc (M)
yield (%)
Scheme 2. Proposed Route to Access 1,2,4-Triazolo[1,5-
a]pyridines Based on the Previously Reported I(III)-
Mediated Synthesis of 2-Substituted Benzimidazoles (eq 2),
Except That the Two Hydrogens Oxidatively Removed in
This Case Are from the Imine and Amine Moieties
PIDA (1.2)
PhIO (1.2)
PIFA (1.2)
PIFA (1.2)
PIFA (1.2)
PIFA (1.2)
PIFA (1.2)
PIFA (1.2)
PIFA (1.2)
PIFA (1.2)
PIFA (1.2)
PIFA (1.0)
PIFA (1.5)
PIFA (1.2)
PIFA (1.2)
DCM
DCM
DCM
DCE
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.05
0.2
40
36
68
78
84
70
60
87
67
88
96
85
96
96
90
c
2
3
4
5
MeCN
EtOAc
toluene
DMF
MeOH
TFE
6
7
8
9
10
11
12
13
14
15
HFIP
HFIP
HFIP
HFIP
HFIP
a
Reaction conditions: 1a (0.5 mmol) and oxidant in solvent at
b
ambient temperature for 10 min unless otherwise stated. Isolated
yields. Reaction mixture heated under reflux for 3 h.
c
some previously reported I(III)-mediated N−N bond forming
reactions, we envisaged that the analogous N-(pyridin-2-
yl)amidines 1 would probably undergo the oxidative N−N
bond formation in a similar manner to give 1,2,4-triazolo[1,5-
a]pyridine product 2.
than that of the methyl-containing substrate, which was
probably due to the relatively low nucleophilicity of the
pyridines affected by the halogens (Table 2, entries 1−4). The
substitution effect of the R2 group was then examined. It was
found that when R2 is an aryl group, bearing either electron-
withdrawing substituents such as halogens and trifluoromethyl
group (Table 2, enties 5−11) or electron-donating substituents
such as methyl and methoxy groups (Table 2, entries 13−15),
it is well tolerated under identical conditions. The reaction was
also shown to be compatible with multiple substituents on the
aromatic ring (Table 2, entry 10). Reaction of 4-methyl-
substituted substrate 1p showed an obvious decrease in the
isolated product yield.16 When a substrate bearing a nitro group
at the para position of the phenyl group was subjected to the
optimal reaction conditions, although substrate 1m was
completely consumed, the reaction resulted in the formation
of some inseparable, polar products, with no detection of the
desired cyclized product (Table 2, entry 12). It is worth noting
that heterocyclic substituents such as pyridinyl and thienyl ring
(2q and 2r, respectively) could also well survive the process
(Table 2, entries 16 and 17, respectively). To our delight, the
method could also be applied to substrates with R2 being an
alkyl group (Table 2, entries 18−20), which greatly expands the
scope of our method. For example, substrate 1s bearing a
benzyl group proceeded smoothly to give cyclized product 2s in
91% yield (Table 2, entry 18). It was gratifying to know the
presence of an alkenyl group in the substrate would not
influence the outcome of the cyclization process (Table 2, entry
19).
N-(Pyridin-2-yl)benzimidamide (1a),11i,14 easily prepared
from the corresponding 2-aminopyridine and benzonitrile,
was used as a model substrate to test the feasibility of the
proposed oxidative cyclization reaction. The initial reaction
mixture of 1a was treated with PhI(OAc)2 in dichloromethane
(DCM) at ambient temperature. This set of conditions indeed
afforded the desired product in 40% yield with full
consumption of the substrate within 30 min (Table 1, entry
1). The other two hypervalent iodine(III) reagents, i.e.,
PhI(OCOCF3)2 and PhIO, were also screened in DCM,
among which PhI(OCOCF3)2 provided the best yield (Table 1,
entries 1−3). To obtain the desired product (2a) in a more
desirable yield, various solvents were tested in the follow-up
solvent screening experiments (Table 1, entries 3−11). Results
showed that the reaction using hexafluoroisopropanol
(HFIP)15 as a solvent afforded the best yield (96%), though
other solvents, i.e., 1,2-dichloroethane (DCE), MeCN, DMF,
and trifluoroethanol (TFE), also provided moderate to good
yields of >70%. Further study indicated that the reaction
performance was not improved by varying the dosage of the
oxidant (Table 1, entries 11−13), while a higher reaction
concentration (0.20 mol/L) proved to have a negative impact
on the yield (Table 1, entries 11, 14, and 15).
With the optimized reaction conditions established (Table 1,
entry 11), the scope of the newly discovered oxidative N−N
bond formation reaction was investigated (Table 2). Because 2a
was afforded in an excellent yield from its corresponding
substrate 1a, the effect of substituents on the pyridine ring (R1)
was first examined. This heterocyclic ring was found to be
tolerant of both electron-rich groups such as methyl (2b) and
electron-deficient groups such as halogens (2c−e). Reactions of
halogen-containing substrates provided yields slightly lower
On the basis of the obtained results, a plausible mechanism
for the cyclization process of 1,2,4-triazolo[1,5-a]pyridines 2
was suggested. As described in Scheme 3, the entire reaction
consists of three simple steps, with intermediate I being first
formed from the reaction of N-(pyridin-2-yl)-imidamide 1 and
PIFA by losing one molecule of TFA and then direct
intramolecular nucleophilic attack of the N atom of the
pyridine ring to generate ammonium ion II,17 which affords the
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Note
a
Table 2. Oxidative Cyclization of N-(Substituted pyridin-2-yl)imidamides to 1,2,4-Triazolo[1,5-a]pyridines
a
b
General condition: 1 (1.0 mmol) and PIFA (1.2 mmol) in HFIP (10 mL) stirred at room temperature for 10 min unless otherwise stated. Isolated
yield.
title compound 2 after rearomatization through the abstraction
of a proton. The mechanism offers straightforward explanations
to two of our observations: (a) why a strongly electron-
withdrawing R2, i.e., NO2, impeded the reaction and (b) why
electron-donating R1, i.e., Me, facilitated the reaction. The
answers are the greatly reduced nucleophilicity of 1, which led
to the failure of the first step, and the increased nucelophilicity
of I in facilitating the second step.
In summary, a convenient and efficient synthesis of 1,2,4-
triazolo[1,5-a]pyridines under mild conditions has been
realized from a variety of N-(substituted pyridin-2-yl)-
imidamides through intramolecular oxidative N−N bond
formation. The method signifies a new PIFA-mediated N−N
bond formation pattern, and the attractive features such as the
wide substrate scope, mild reaction conditions, and high
reaction yields qualify its click chemistry efficiency.
EXPERIMENTAL SECTION
■
General Information. All reactions were conducted at room
temperature without precaution of air and mixtures stirred magneti-
cally. 1H and 13C NMR spectra were recorded on a 600 MHz
spectrometer at 25 °C. Chemical shift values are given in parts per
million and referred to the internal standard, TMS (tetramethylsilane).
The peak patterns are indicated as follows: s, singlet; d, doublet; t,
triplet; q, quartet; m, multiplet; dd, doublet of doublets; td, triplet of
doublets; br s, broad singlet. The coupling constants (J) are reported
in hertz. High-resolution mass spectrometry (HRMS) was conducted
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Note
1
mp 157−158 °C; H NMR (600 MHz, CDCl3) δ 10.25 (br s, 1H),
8.27 (d, 1H, J = 3.0), 7.90−7.89 (m, 2H), 7.59 (dd, 1H, J = 8.4, 3.0),
7.48−7.43 (m, 3H), 7.21 (d, 1H, J = 9.0), 5.98 (br s, 1H); 13C NMR
(150 MHz, CDCl3) δ 161.2, 159.1, 144.4, 137.4, 137.2, 130.8, 128.7,
Scheme 3. Proposed Mechanism for the Construction of
1,2,4-Triazolo[1,5-a]pyridines
126.9, 125.1, 123.5; HRMS (ESI) calcd for C12H1135ClN3 [M + H+]
+
232.0636, found 232.0635. Anal. Calcd for C12H10ClN3: C, 62.21; H,
4.35; N, 18.14. Found: C, 62.49; H, 4.29; N, 17.99.
N-(3,5-Dibromopyridin-2-yl)benzimidamide (1e). Following gen-
eral procedure A, 1e was isolated as a white solid: yield 1.56 g, 44%;
mp 128−129 °C; 1H NMR (600 MHz, CDCl3) δ 9.88 (br s, 1H), 8.28
(d, 1H, J = 2.4), 8.04 (d, 1H, J = 2.4), 8.02 (d, 2H, J = 7.8), 7.50 (t,
1H, J = 7.2), 7.45 (t, 2H, J = 7.2), 6.14 (br s, 1H); 13C NMR (150
MHz, CDCl3) δ 159.1, 157.9, 145.6, 143.0, 136.4, 131.3, 128.7, 127.3,
+
119.1, 112.0; HRMS (ESI) calcd for C12H1079Br2N3 [M + H+]
353.9236, found 353.9235. Anal. Calcd for C12H9Br2N3: C, 40.60; H,
2.56; N, 11.84. Found: C, 40.89; H, 2.50; N, 11.52.
4-Fluoro-N-(pyridin-2-yl)benzimidamide (1f). Following general
procedure A, 1f was isolated as a light yellow solid: yield 1.14 g, 53%;
mp 163−164 °C; H NMR (600 MHz, CDCl3) δ 10.52 (br s, 1H),
on a Q-TOF micro spectrometer. Elemental (C, H, N) analysis was
conducted using a Vario Micro cube analyzer. Melting points were
determined with a national micromelting point apparatus without
corrections. Reagents and solvents were purchased as reagent grade
and were used without further purification. Flash column chromatog-
raphy was performed over silica gel 200−300 mesh, and the eluent was
a mixture of ethyl acetate and petroleum ether.
General Procedure for the Preparation of N-Substituted
Amidines 1. General Procedure A.11i To a stirred solution of
substituted 2-aminopyridine (10 mmol) in DMF (5.0 mL) was added
NaH (60% dispersion in mineral oil, 12 mmol) at 0 °C, and the
mixture was stirred at the same temperature for 30 min. Substituted
benzonitrile (12 mmol) was then added to the reaction mixture and
the mixture stirred at room temperature until TLC indicated the total
consumption of the substituted 2-aminopyridine. The reaction was
quenched by the addition of 5% aqueous NaHCO3 (10 mL) and the
mixture extracted with EtOAc. The extract was washed with brine and
dried over Na2SO4. The solvent was then evaporated, and the residue
was purified by column chromatography using a mixture of petroleum
ether and EtOAc as the eluent to afford the desired N-substituted
amidine 1.
1
8.33 (dd, 1H, J = 4.8, 1.8), 7.92 (dd, 2H, J = 8.4, 6.0), 7.65 (td, 1H, J =
7.5, 1.8), 7.26 (d, 1H, J = 7.8), 7.13 (t, 2H, J = 8.7), 6.94 (t, 1H, J =
6.0), 5.97 (br s, 1H); 13C NMR (150 MHz, CDCl3) δ 164.3 (d, J =
247.5), 162.8, 158.0, 146.0, 137.6, 133.6, 129.1 (d, J = 7.5), 122.5,
+
118.0, 115.6 (d, J = 21.0); HRMS (ESI) calcd for C12H11FN3 [M +
H+] 216.0932, found 216.0932. Anal. Calcd for C12H10FN3: C, 66.97;
H, 4.68; N, 19.52. Found: C, 67.21; H, 4.65; N, 19.17.
2-Chloro-N-(pyridin-2-yl)benzimidamide (1i). Following general
procedure A, 1i was isolated as a white solid: yield 1.64 g, 71%; mp
1
104−105 °C; H NMR (600 MHz, CDCl3) δ 10.72 (br s, 1H), 8.34
(d, 1H, J = 3.6), 7.69−7.67 (m, 1H), 7.64 (td, 1H, J = 7.8, 1.8), 7.43−
7.41 (m, 1H), 7.34−7.32 (m, 2H), 7.23 (d, 1H, J = 7.2), 6.95 (t, 1H, J
= 6.3), 5.90 (br s, 1H); 13C NMR (150 MHz, CDCl3) δ 162.8, 158.5,
146.0, 137.6, 137.2, 131.4, 130.5, 130.5, 130.2, 127.1, 122.4, 118.2;
+
HRMS (ESI) calcd for C12H1135ClN3 [M + H+] 232.0636, found
232.0635. Anal. Calcd for C12H10ClN3: C, 62.21; H, 4.35; N, 18.14.
Found: C, 62.43; H, 4.39; N, 17.81.
2,6-Dichloro-N-(pyridin-2-yl)benzimidamide (1k). Following gen-
eral procedure A, 1k was isolated as a white solid: yield 1.73 g, 65%;
1
General Procedure B.14 Substituted benzonitrile (10 mmol) was
taken in a dry round-bottom flask, and to this was added a substituted
2-aminopyridine (10 mmol). The flask was heated, after fitting a dry
condenser along with a guard tube, in an oil bath over a temperature
range of 80−90 °C while its contents were being stirred. After 30 min,
SnCl4 (1.4 mL, 12 mmol) was added to the flask. After that addition,
the temperature was increased to 100−110 °C, and the contents of the
flask were heated for 3−4 h. The mixture was cooled to room
temperature, and the solid, thus formed, was crushed into powder and
dissolved in hot water. The aqueous suspension was made alkaline
with 10% NaOH and extracted with CH2Cl2 (3 × 100 mL). The
organic layer was dried over anhydrous Na2SO4. After the solvent had
been evaporated under reduced pressure, crude amidine was obtained
and purified by column chromatography using a mixture of petroleum
ether and EtOAc as the eluent to afford the desired N-substituted
amidine 1.
mp 147−148 °C; H NMR (600 MHz, CDCl3) δ 10.63 (br s, 1H),
8.36−8.35 (m, 1H), 7.65 (t, 1H, J = 7.5), 7.35 (d, 2H, J = 7.8), 7.27−
7.22 (m, 2H), 6.97 (t, 1H, J = 6.0), 5.70 (br s, 1H); 13C NMR (150
MHz, CDCl3) δ 162.6, 155.9, 146.1, 137.7, 136.4, 133.6, 130.3, 128.3,
+
122.4, 118.6; HRMS (ESI) calcd for C12H1035Cl2N3 [M + H+]
266.0246, found 266.0246. Anal. Calcd for C12H9Cl2N3: C, 54.16; H,
3.41; N, 15.79. Found: C, 54.41; H, 3.50; N, 15.45.
N-(Pyridin-2-yl)-2-(trifluoromethyl)benzimidamide (1l). Following
general procedure B, 1l was isolated as a white solid: yield 1.75 g, 66%;
1
mp 139−140 °C; H NMR (600 MHz, CDCl3) δ 10.61 (br s, 1H),
8.33 (d, 1H, J = 3.6), 7.72 (d, 1H, J = 7.8), 7.68 (d, 1H, J = 7.8), 7.64
(td, 1H, J = 7.8, 1.8), 7.60 (t, 1H, J = 7.5), 7.52 (t, 1H, J = 7.8), 7.20
(d, 1H, J = 8.4), 6.95 (t, 1H, J = 6.0), 5.70 (br s, 1H); 13C NMR (150
MHz, CDCl3) δ 162.7, 158.9, 146.0, 137.7, 137.3, 132.1, 130.0, 129.3,
127.7 (q, J = 31.0), 126.5 (q, J = 5.0), 123.9 (q, J = 272.0), 122.3,
118.4; HRMS (ESI) calcd for C13H11F3N3+ [M + H+] 266.0900, found
266.0900. Anal. Calcd for C13H10F3N3: C, 58.87; H, 3.80; N, 15.84.
Found: C, 59.04; H, 3.72; N, 15.61.
Following procedure A, known N-substituted amidines 1a,11i 1d,14
1g and 1h,14 and 1j14 were prepared in 65, 42, 70, 68, and 84% yields,
1
4-Nitro-N-(pyridin-2-yl)benzimidamide (1m). Following general
procedure B, 1m was isolated as a yellow solid: yield 1.28 g, 53%; mp
185−186 °C; 1H NMR (600 MHz, CDCl3) δ 10.52 (br s, 1H), 8.38−
8.37 (m, 1H), 8.31 (d, 2H, J = 9.0), 8.11 (d, 2H, J = 8.4), 7.70 (td, 1H,
J = 7.8, 1.8), 7.30 (d, 1H, J = 7.8), 7.01−6.99 (m, 1H), 6.03 (br s, 1H);
13C NMR (150 MHz, CDCl3) δ 162.3, 156.5, 149.1, 146.1, 143.3,
respectively. The properties and H NMR data of 1a, 1d, 1g, 1h, and
1j were consistent with those in the literature. Novel N-substituted
amidines 1b, 1c, 1e, 1f, 1i, and 1k−u thus obtained were characterized
as follows.
N-(3-Methylpyridin-2-yl)benzimidamide (1b).11b Following gen-
eral procedure A, 1b was isolated as a yellow solid: yield 1.20 g, 57%;
mp 69−70 °C (lit.11b 68−69 °C); 1H NMR (600 MHz, CDCl3) δ 9.85
(br s, 1H), 8.18 (d, 1H, J = 4.8), 7.97 (d, 2H, J = 7.2), 7.48 (d, 1H, J =
7.2), 7.46−7.42 (m, 3H), 6.84 (dd, 1H, J = 7.2, 4.8), 6.18 (br s, 1H),
2.48 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 161.1, 157.3, 143.6,
138.0, 137.5, 130.6, 130.4, 128.5, 127.1, 117.9, 18.6; HRMS (ESI)
+
137.8, 128.1, 123.8, 122.9, 118.7; HRMS (ESI) calcd for C12H11N4O2
[M + H+] 243.0877, found 243.0877. Anal. Calcd for C12H10N4O2: C,
59.50; H, 4.16; N, 23.13. Found: C, 59.65; H, 4.23; N, 22.98.
2-Methyl-N-(pyridin-2-yl)benzimidamide (1n). Following general
procedure B, 1n was isolated as a yellow solid: yield: 0.84 g, 40%; mp
98−99 °C; H NMR (600 MHz, CDCl3) δ 10.58 (br s, 1H), 8.32 (d,
1H, J = 4.2), 7.62 (t, 1H, J = 7.5), 7.46 (d, 1H, J = 7.2), 7.31−7.28 (m,
1H), 7.24−7.19 (m, 3H), 6.93 (t, 1H, J = 6.0), 5.67 (br s, 1H), 2.50 (s,
+
1
calcd for C13H14N3 [M + H+] 212.1182, found 212.1185.
N-(5-Chloropyridin-2-yl)benzimidamide (1c). Following general
procedure A, 1c was isolated as a light pink solid: yield 1.04 g, 45%;
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Note
3H); 13C NMR (150 MHz, CDCl3) δ 162.9, 161.2, 146.0, 138.4,
137.6, 135.5, 130.9, 129.2, 127.7, 125.9, 122.2, 118.0, 19.6; HRMS
(ESI) calcd for C13H14N3+ [M + H+] 212.1182, found 212.1182. Anal.
Calcd for C13H13N3: C, 73.91; H, 6.20; N, 19.89. Found: C, 74.16; H,
6.09; N, 19.63.
3-Methoxy-N-(pyridin-2-yl)benzimidamide (1o). Following gen-
eral procedure B, 1o was isolated as a white solid: yield 1.32 g, 58%;
mp 85−86 °C; 1H NMR (600 MHz, CDCl3) δ 10.52 (br s, 1H), 8.33
(dd, 1H, J = 5.1, 1.5), 7.64 (td, 1H, J = 7.8, 1.8), 7.50 (s, 1H), 7.43 (d,
1H, J = 7.8), 7.34 (t, 1H, J = 7.8), 7.28 (d, 1H, J = 7.8), 7.01 (dd, 1H, J
= 7.8, 2.4), 6.94−6.92 (m, 1H), 6.01 (br s, 1H), 3.87 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ 162.9, 159.8, 159.0, 146.0, 139.0, 137.5,
129.6, 122.5, 119.0, 117.9, 116.7, 112.4, 55.4; HRMS (ESI) calcd for
C13H14N3O+ [M + H+] 228.1131, found 228.1127. Anal. Calcd for
C13H13N3O: C, 68.70; H, 5.77; N, 18.49. Found: C, 68.95; H, 5.71; N,
18.20.
4-Methoxy-N-(4-methylpyridin-2-yl)benzimidamide (1p). Follow-
ing general procedure B, 1p was isolated as a white solid: yield 1.23 g,
51%; mp 97−98 °C; 1H NMR (600 MHz, CDCl3) δ 10.15 (br s, 1H),
8.18 (d, 1H, J = 4.8), 7.87 (d, 2H, J = 9.0), 7.08 (s, 1H), 6.94 (d, 2H, J
= 8.4), 6.74 (d, 1H, J = 6.6), 6.09 (br s, 1H), 3.84 (s, 3H), 2.32 (s,
3H); 13C NMR (150 MHz, CDCl3) δ 163.1, 161.5, 158.5, 148.4,
145.7, 129.9, 128.5, 122.6, 119.0, 113.8, 55.4, 21.0; HRMS (ESI) calcd
for C14H16N3O+ [M + H+] 242.1288, found 242.1283. Anal. Calcd for
C14H15N3O: C, 69.69; H, 6.27; N, 17.41. Found: C, 69.80; H, 6.19; N,
17.09.
1H), 2.34 (t, 2H, J = 7.8), 1.72−1.67 (m, 2H), 1.44−1.40 (m, 2H),
0.94 (t, 3H, J = 7.2); 13C NMR (150 MHz, CDCl3) δ 164.2, 162.9,
145.9, 137.4, 121.2, 117.4, 38.6, 29.8, 22.5, 13.9; HRMS (ESI) calcd
+
for C10H16N3 [M + H+] 178.1339, found 178.1339. Anal. Calcd for
C10H15N3: C, 67.76; H, 8.53; N, 23.71. Found: C, 67.88; H, 8.48; N,
23.64.
General Procedure for the Preparation of 1,2,4-Triazolo[1,5-
a]pyridines 2. General Procedure. To a stirred solution of N-
substituted amidine 1 (1.0 mmol) in HFIP (10 mL) was added PIFA
(1.2 mmol) at room temperature. The resulting mixture was stirred at
the same temperature until TLC indicated the total consumption of
the substrate (within 10 min). The reaction was quenched by the
addition of 5% aqueous NaHCO3 (50 mL) and the mixture extracted
with CH2Cl2 (50 mL). The extract was washed with brine and dried
over Na2SO4. The solvent was then evaporated, and the residue was
purified by column chromatography using a mixture of petroleum and
EtOAc as the eluent to afford the desired 1,2,4-triazolo[1,5-a]pyridine
2.
Following this general procedure, known 1,2,4-triazolo[1,5-a]-
pyridines 2a,11i 2f−h,11i 2j,11i and 2o−r11i were prepared in 95, 93,
90, 91, 94, 86, 74, 94, and 96% yields, respectively. The properties and
1H NMR data of 2a, 2f−h, 2j, and 2o−r were consistent with those in
the literature. Novel 1,2,4-triazolo[1,5-a]pyridines 2b−e, 2i, 2k, 2l, 2n,
and 2s−u thus obtained were characterized as follows.
2-Phenyl-[1,2,4]triazolo[1,5-a]pyridine (2a).11i Following the
general procedure, 2a was isolated as a white solid: yield 185 mg,
95%; mp 138−139 °C (lit.11b 138 °C); 1H NMR (600 MHz, CDCl3)
δ 8.59 (d, 1H, J = 6.6), 8.30−8.29 (m, 2H), 7.76 (d, 1H, J = 8.4),
7.50−7.45 (m, 4H), 6.9 (td, 1H, J = 6.9, 1.2).
N-(Pyridin-2-yl)isonicotinimidamide (1q). Following general pro-
cedure A, 1q was isolated as a light yellow solid: yield 1.50 g, 76%; mp
1
164−165 °C; H NMR (600 MHz, d6-DMSO) δ 10.25 (br s, 1H),
8-Methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyridine (2b).11b Follow-
ing the general procedure, 2b was isolated as a white solid: yield 194
8.74 (dd, 2H, J = 4.8, 1.5), 8.44 (br s, 1H), 8.39 (dd, 1H, J = 5.1, 1.5),
7.99 (d, 2H, J = 5.4), 7.76 (td, 1H, J = 7.8, 1.8), 7.19 (d, 1H, J = 7.8),
7.06−7.04 (m, 1H); 13C NMR (150 MHz, d6-DMSO) δ 162.3, 155.8,
149.9, 146.3, 143.6, 137.8, 121.9, 121.3, 118.0; HRMS (ESI) calcd for
mg, 93%; mp 100−101 °C (lit.11b 97−98 °C); H NMR (600 MHz,
1
CDCl3) δ 8.42 (d, 1H, J = 7.2), 8.30 (d, 2H, J = 7.2), 7.50−7.47 (m,
2H), 7.45−7.43 (m, 1H), 7.21 (d, 1H, J = 6.6), 6.84 (t, 1H, J = 6.9);
13C NMR (150 MHz, CDCl3) δ 163.7, 152.2, 131.1, 129.9, 128.7,
128.1, 127.4, 127.0, 125.9, 113.4, 17.0; HRMS (ESI) calcd for
+
C11H11N4 [M + H+] 199.0978, found 199.0978. Anal. Calcd for
C11H10N4: C, 66.65; H, 5.08; N, 28.26. Found: C, 66.77; H, 5.14; N,
27.90.
N-(Pyridin-2-yl)thiophene-2-carboximidamide (1r). Following
+
C13H12N3 [M + H+] 210.1026, found 210.1027.
general procedure A, 1r was isolated as a light yellow solid: yield
1.50 g, 74%; mp 133−134 °C; H NMR (600 MHz, CDCl3) δ 8.30
6-Chloro-2-phenyl-[1,2,4]triazolo[1,5-a]pyridine (2c). Following
1
the general procedure, 2c was isolated as a white solid: yield 198
1
mg, 86%; mp 168−169 °C; H NMR (600 MHz, CDCl3) δ 8.63 (s,
(dd, 1H, J = 5.1, 1.5), 7.62 (td, 1H, J = 7.8, 1.8), 7.47 (d, 1H, J = 3.6),
7.43 (dd, 1H, J = 5.4, 0.6), 7.23 (d, 1H, J = 7.8), 7.07 (dd, 1H, J = 4.8,
3.6), 6.92−6.90 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 162.6,
153.5, 146.1, 142.2, 137.5, 129.5, 127.5, 126.0, 122.4, 117.9; HRMS
(ESI) calcd for C10H10N3S+ [M + H+] 204.0584, found 204.0589.
Anal. Calcd for C10H9N3S: C, 59.09; H, 4.46; N, 20.67. Found: C,
59.28; H, 4.40; N, 20.43.
1H), 8.25 (d, 2H, J = 6.6), 7.68 (d, 1H, J = 9.0), 7.49−7.45 (m, 4H);
13C NMR (150 MHz, CDCl3) δ 164.9, 150.3, 131.0, 130.3, 128.8,
127.3, 126.6, 121.6, 116.4 (one carbon peak was missing because of
+
overlapping); HRMS (ESI) calcd for C12H935ClN3 [M + H+]
230.0480, found 230.0480. Anal. Calcd for C12H8ClN3: C, 62.76; H,
3.51; N, 18.30. Found: C, 62.85; H, 3.48; N, 18.21.
2-Phenyl-N-(pyridin-2-yl)acetimidamide (1s). Following general
procedure B, 1s was isolated as a light yellow solid: yield 1.46 g, 69%;
mp 90−91 °C; 1H NMR (600 MHz, CDCl3) δ 10.34 (br s, 1H), 8.24
(dd, 1H, J = 5.1, 1.5), 7.63−7.60 (m, 1H), 7.37−7.35 (m, 4H), 7.30−
7.28 (m, 1H), 7.16 (d, 1H, J = 7.8), 6.90−6.87 (m, 1H), 5.34 (br s,
1H), 3.77 (s, 2H); 13C NMR (150 MHz, CDCl3) δ 162.8, 162.1,
145.9, 137.5, 136.1, 129.5, 128.9, 127.3, 121.5, 117.7, 45.0; HRMS
(ESI) calcd for C13H14N3+ [M + H+] 212.1177, found 212.1180. Anal.
Calcd for C13H13N3: C, 73.91; H, 6.20; N, 19.89. Found: C, 74.10; H,
6.28; N, 19.58.
6-Bromo-2-phenyl-[1,2,4]triazolo[1,5-a]pyridine (2d). Following
the general procedure, 2d was isolated as a white solid: yield 238 mg,
1
87%; mp 165−166 °C; H NMR (600 MHz, CDCl3) δ 8.74 (d, J =
1.2, 1H), 8.27−8.25 (m, 2H), 7.65 (d, 1H, J = 9.0), 7.57 (dd, 1H, J =
9.0, 1.8), 7.51−7.47 (m, 3H); 13C NMR (150 MHz, CDCl3) δ 164.7,
150.4, 133.1, 130.4, 130.3, 128.8, 127.4, 123.3, 116.8, 107.7; HRMS
+
(ESI) calcd for C12H979BrN3 [M + H+] 273.9974, found 273.9973.
Anal. Calcd for C12H8BrN3: C, 52.58; H, 2.94; N, 15.33. Found: C,
52.70; H, 2.99; N, 15.22.
6,8-Dibromo-2-phenyl-[1,2,4]triazolo[1,5-a]pyridine (2e). Follow-
2-Cyclohexenyl-N-(pyridin-2-yl)acetimidamide (1t). Following
ing the general procedure, 2e was isolated as a white solid: yield 314
1
general procedure B, 1t was isolated as a light brown liquid: yield
mg, 89%; mp 163−165 °C; H NMR (600 MHz, CDCl3) δ 8.66 (d,
1
1.18 g, 55%; H NMR (600 MHz, CDCl3) δ 10.21 (br s, 1H), 8.18−
1H, J = 1.2), 8.28−8.27 (m, 2H), 7.80 (d, 1H, J = 1.2), 7.49−7.47 (m,
3H); 13C NMR (150 MHz, CDCl3) δ 164.8, 149.7, 134.9. 130.6,
129.8, 128.7, 128.0, 127.6, 110.1, 106.8; HRMS (ESI) calcd for
8.18 (m, 1H), 7.52 (t, 1H, J = 7.8), 7.05 (d, 1H, J = 7.2), 6.80 (t, 1H, J
= 6.0), 5.73 (br s, 1H), 5.61 (s, 1H), 2.98 (s, 2H), 1.99−1.94 (m, 4H),
1.55−1.49 (m, 4H); 13C NMR (150 MHz, CDCl3) δ 162.8, 162.0,
145.9, 137.5, 134.1, 126.7, 121.3, 117.6, 47.5, 27.9, 25.4, 22.8, 22.1;
+
C12H879Br2N3 [M + H+] 351.9079, found 351.9077. Anal. Calcd for
C12H7Br2N3: C, 40.83; H, 2.00; N, 11.90. Found: C, 40.92; H, 2.08; N,
11.71.
+
HRMS (ESI) calcd for C13H18N3 [M + H+] 216.1495, found
216.1495. Anal. Calcd for C13H17N3: C, 72.52; H, 7.96; N, 19.52.
Found: C, 72.81; H, 7.89; N, 19.17.
N-(Pyridin-2-yl)pentanimidamide (1u). Following general proce-
dure B, 1u was isolated as a yellow liquid: yield 1.02 g, 58%; 1H NMR
(600 MHz, CDCl3) δ 10.20 (br s, 1H), 8.57 (d, 1H, J = 4.2), 7.58 (t,
1H, J = 7.5), 7.11 (d, 1H, J = 7.8), 6.86 (t, 1H, J = 6.0), 5.56 (br s,
2-(4-Fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridine (2f).11i Follow-
ing the general procedure, 2f was isolated as a yellow solid: yield
198 mg, 93%; mp 181−182 °C (lit.11i 173−174 °C); H NMR (600
1
MHz, CDCl3) δ 8.59 (d, 1H, J = 6.6), 8.28 (dd, 2H, J = 8.4, 5.4), 7.75
(d, 1H, J = 9.0), 7.51 (t, 1H, J = 7.8), 7.18 (t, 2H, J = 8.7), 7.01 (t, 1H,
J = 6.6).
4691
dx.doi.org/10.1021/jo500298j | J. Org. Chem. 2014, 79, 4687−4693

The Journal of Organic Chemistry
Note
2-(4-Chlorophenyl)-[1,2,4]triazolo[1,5-a]pyridine (2g).11i Follow-
ing the general procedure, 2g was isolated as a white solid: yield 206
mg, 90%; mp 225−226 °C (lit.11i 220−221 °C); 1H NMR (600 MHz,
CDCl3) δ 8.59 (d, 1H, J = 6.6), 8.23 (d, 2H, J = 8.4), 7.75 (d, 1H, J =
9.0), 7.52 (t, 1H, J = 7.8), 7.47 (d, 2H, J = 7.8), 7.02 (t, 1H, J = 6.9).
2-(4-Bromophenyl)-[1,2,4]triazolo[1,5-a]pyridine (2h).11i Follow-
ing the general procedure, 2h was isolated as a white solid: yield 249
mg, 91%; mp 234−235 °C (lit.11i 229−230 °C); 1H NMR (600 MHz,
CDCl3) δ 8.59 (d, 1H, J = 7.2), 8.16 (d, 2H, J = 8.4), 7.76 (d, 1H, J =
9.0), 7.63 (d, 2H, J = 8.4), 7.53 (t, 1H, J = 7.5), 7.03 (t, 1H, J = 6.6).
2-(2-Chlorophenyl)-[1,2,4]triazolo[1,5-a]pyridine (2i). Following
the general procedure, 2i was isolated as a white solid: yield 209 mg,
91%; mp 122−123 °C; 1H NMR (600 MHz, CDCl3) δ 8.66 (d, 1H, J
= 7.2), 8.02−8.01 (m, 1H), 7.82 (d, 1H, J = 9.0), 7.56−7.53 (m, 2H),
7.41−7.38 (m, 2H), 7.05 (td, 1H, J = 6.6, 1.2); 13C NMR (150 MHz,
CDCl3) δ 162.9, 151.0, 133.2, 132.2, 130.8, 130.7, 130.0, 129.7, 128.5,
126.8, 116.7, 113.9; HRMS (ESI) calcd for C12H835ClN3Na+ [M +
Na+] 252.0299, found 252.0298. Anal. Calcd for C12H8ClN3: C, 62.76;
H, 3.51; N, 18.30. Found: C, 62.89; H, 3.45; N, 18.13.
CDCl3) δ 8.78 (d, 2H, J = 5.4), 8.64 (d, 1H, J = 7.2), 8.16 (d, 2H, J =
6.6), 7.81 (d, 1H, J = 9.0), 7.58 (t, 1H, J = 7.8), 7.09 (t, 1H, J = 6.9).
2-(Thiophen-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (2r).11i Following
the general procedure, 2r was isolated as a yellow solid: yield 193 mg,
96%; mp 168−169 °C (lit.18 165 °C); 1H NMR (600 MHz, CDCl3) δ
8.57 (d, 1H, J = 7.2), 7.90 (dd, 1H, J = 3.6, 1.2), 7.74 (d, 1H, J = 9.0),
7.53−7.50 (m, 1H), 7.46 (dd, 1H, J = 5.1, 4.2), 7.17 (dd, 1H, J = 4.8,
3.6), 7.01 (td, 1H, J = 6.6, 1.2).
2-Benzyl-[1,2,4]triazolo[1,5-a]pyridine (2s). Following the general
procedure, 2s was isolated as a yellow solid: yield 190 mg, 91%; mp
80−81 °C; 1H NMR (600 MHz, CDCl3) δ 8.51 (d, 1H, J = 6.6), 7.66
(d, 1H, J = 8.4), 7.45 (t, 1H, J = 7.8), 7.41 (d, 2H, J = 7.2), 7.31 (t, 2H,
J = 7.8), 7.22 (t, 1H, J = 7.5), 6.94 (t, 1H, J = 6.9), 4.27 (s, 2H); 13C
NMR (150 MHz, CDCl3) δ 166.2, 151.3, 137.7, 129.4, 129.0, 128.6,
128.2, 126.7, 116.2, 113.3, 35.4; HRMS (ESI) calcd for C13H12N3+ [M
+ H+] 210.1026, found 210.1026. Anal. Calcd for C13H11N3: C, 74.62;
H, 5.30; N, 20.08. Found: C, 74.75; H, 5.37; N, 19.97.
2-(Cyclohexenylmethyl)-[1,2,4]triazolo[1,5-a]pyridine (2t). Fol-
lowing the general procedure, 2t was isolated as a light yellow liquid:
1
2-(3-Chlorophenyl)-[1,2,4]triazolo[1,5-a]pyridine (2j).11i Follow-
ing the general procedure, 2j was isolated as a white solid: yield 198
mg, 86%; mp 182−184 °C (lit.11i 177−178 °C); 1H NMR (600 MHz,
CDCl3) δ 8.58 (d, 1H, J = 6.6), 8.29 (s, 1H), 8.17−8.16 (m, 1H), 7.75
(d, 1H, J = 9.0), 7.51 (t, 1H, J = 8.1), 7.43−7.40 (m, 2H), 7.01 (t, 1H,
J = 6.9).
yield 187 mg, 88%; H NMR (600 MHz, CDCl3) δ 8.53 (d, 1H, J =
6.6), 7.68 (d, 1H, J = 9.0), 7.46 (t, 1H, J = 8.1), 6.96 (t, 1H, J = 6.9),
5.63 (s, 1H), 3.58 (s, 2H), 2.04−2.03 (m, 4H), 1.65−1.61 (m, 2H),
1.58−1.54 (m, 2H); 13C NMR (150 MHz, CDCl3) δ 165.8, 151.2,
134.3, 129.2, 128.1, 124.0, 116.1, 113.1, 37.7, 28.2, 25.2, 22.7, 22.1;
+
HRMS (ESI) calcd for C13H16N3 [M + H+] 214.1339, found
214.1339. Anal. Calcd for C13H15N3: C, 73.21; H, 7.09; N, 19.70.
Found: C, 73.56; H, 7.14; N, 19.48.
2-(2,6-Dichlorophenyl)-[1,2,4]triazolo[1,5-a]pyridine (2k). Follow-
ing the general procedure, 2k was isolated as a white solid: yield 238
2-Butyl-[1,2,4]triazolo[1,5-a]pyridine (2u). Following the general
1
mg, 90%; mp 109−110 °C; H NMR (600 MHz, CDCl3) δ 8.69 (d,
1
procedure, 2u was isolated as a yellow liquid: yield 150 mg, 86%; H
1H, J = 6.6), 7.92 (d, 1H, J = 9.0), 7.63 (t, 1H, J = 7.8), 7.45 (d, 2H, J
= 7.8), 7.37 (t, 1H, J = 8.1), 7.14 (t, 1H, J = 6.9); 13C NMR (150
MHz, CDCl3) δ 160.0, 150.7, 136.0, 131.3, 130.4, 130.1, 128.7, 128.1,
NMR (600 MHz, CDCl3) δ 8.41 (d, 1H, J = 6.6), 7.56 (d, 1H, J = 9.0),
7.35 (t, 1H, J = 7.8), 6.84 (t, 1H, J = 6.9), 2.84 (t, 2H, J = 7.8), 1.79−
1.74 (m, 2H), 1.39−1.33 (m, 2H), 0.87 (t, 3H, J = 7.5); 13C NMR
(150 MHz, CDCl3) δ 167.6, 151.1, 129.1, 127.9, 115.8, 112.9, 30.4,
+
116.8, 114.6; HRMS (ESI) calcd for C12H835Cl2N3 [M + H+]
+
28.4, 22.4, 13.7; HRMS (ESI) calcd for C10H14N3 [M + H+]
264.0090, found 264.0090. Anal. Calcd for C12H7Cl2N3: C, 54.57; H,
2.67; N, 15.91. Found: C, 54.70; H, 2.61; N, 15.74.
176.1182, found 176.1182. Anal. Calcd for C10H13N3: C, 68.15; H,
2-[2-(Trifluoromethyl)phenyl]-[1,2,4]triazolo[1,5-a]pyridine (2l).
Following the general procedure, 2l was isolated as a light brown
solid: yield 234 mg, 89%; mp 81−82 °C; 1H NMR (600 MHz, CDCl3)
δ 8.64 (d, 1H, J = 7.2), 7.90 (d, 1H, J = 7.8), 7.85 (d, 1H, J = 7.8), 7.81
(d, 1H, J = 9.0), 7.66 (t, 1H, J = 7.2), 7.60 (t, 1H, J = 7.5), 7.57−7.54
(m, 1H), 7.06 (td, 1H, J = 6.9, 1.2); 13C NMR (150 MHz, CDCl3) δ
163.1, 151.1, 132.4, 131.6, 130.4, 129.7, 129.6, 129.3 (q, J = 31.5),
128.5, 126.7 (q, J = 5.0), 123.8 (q, J = 272.0), 116.8, 114.0; HRMS
8.01; N, 23.84. Found: C, 68.23; H, 8.06; N, 23.64.
ASSOCIATED CONTENT
* Supporting Information
Spectral data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
■
S
+
(ESI) calcd for C13H9F3N3 [M + H+] 264.0743, found 264.0746.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: duyunfeier@tju.edu.cn.
*E-mail: kangzhao@tju.edu.cn.
■
Anal. Calcd for C13H8F3N3: C, 59.32; H, 3.06; N, 15.96. Found: C,
59.39; H, 3.11; N, 15.77.
2-o-Tolyl-[1,2,4]triazolo[1,5-a]pyridine (2n). Following the general
procedure, 2n was isolated as a white solid: yield 190 mg, 91%; mp
95−96 °C; 1H NMR (600 MHz, CDCl3) δ 8.61 (d, 1H, J = 6.6), 8.07
(d, 1H, J = 7.8), 7.77 (d, 1H, J = 9.0), 7.51−7.48 (m, 1H), 7.36−7.30
(m, 3H), 6.99 (td, 1H, J = 6.9, 1.2), 2.72 (s, 3H); 13C NMR (150
MHz, CDCl3) δ 165.2, 150.9, 137.8, 131.3, 130.3, 130.2, 129.5, 129.3,
128.3, 125.9, 116.5, 113.4, 21.7; HRMS (ESI) calcd for C13H12N3+ [M
+ H+] 210.1026, found 210.1031. Anal. Calcd for C13H11N3: C, 74.62;
H, 5.30; N, 20.08. Found: C, 74.75; H, 5.23; N, 19.90.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge the National Natural Science Foundation of
China (21072148), the Foundation (B) for Peiyang Scholar-
Young Core Faculty of Tianjin University (2013XR-0144), the
Innovation Foundation of Tianjin University (2013XJ-0005),
and the National Basic Research Project (2014CB932200) for
financial support.
2-(3-Methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridine (2o).11i Fol-
lowing the general procedure, 2o was isolated as a white solid: yield
194 mg, 86%; mp 106−108 °C (lit.11i 106−108 °C); H NMR (600
1
MHz, CDCl3) δ 8.61 (d, 1H, J = 6.6), 7.90 (d, 1H, J = 7.8), 7.84−7.84
(m, 1H), 7.77 (d, 1H, J = 9.0), 7.54−7.51 (m, 1H), 7.41 (t, 1H, J =
8.1), 7.04−7.01 (m, 2H), 3.93 (s, 3H).
REFERENCES
■
2-(4-Methoxyphenyl)-7-methyl-[1,2,4]triazolo[1,5-a]pyridine
(1) For selected reviews on hypervalent iodine reagents, see:
(a) Stang, P. J. J. Org. Chem. 2003, 68, 2997. (b) Wirth, T. Angew.
Chem., Int. Ed. 2005, 44, 3656. (c) Moriarty, R. M. J. Org. Chem. 2005,
70, 2893. (d) Richardson, R. D.; Wirth, T. Angew. Chem., Int. Ed. 2006,
45, 4402. (e) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299.
(f) Dohi, T.; Kita, Y. Chem. Commun. 2009, 16, 2073. (g) Zhdankin, V.
V. J. Org. Chem. 2011, 76, 1185.
(2p).11i Following the general procedure, 2p was isolated as a white
solid: yield 177 mg, 74%; mp 166−167 °C (lit.11i 165−166 °C); H
1
NMR (600 MHz, CDCl3) δ 8.42 (d, 1H, J = 7.2), 8.20 (d, 2H, J = 8.4),
7.47 (s, 1H), 7.01 (d, 2H, J = 9.0), 6.78 (dd, 1H, J = 7.2, 1.5), 3.87 (s,
3H), 2.47 (s, 3H).
2-(Pyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyridine (2q).11i Following
the general procedure, 2q was isolated as a yellow solid: yield 184
(2) For selected reviews on hypervalent iodine reagent-mediated
construction of heterocycles, see: (a) Ciufolini, M. A.; Braun, N. A.;
1
1
mg, 94%; mp 194−195 °C (lit. 190−192 °C); H NMR (600 MHz,
4692
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The Journal of Organic Chemistry
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(16) Considering the relatively lower yield obtained for 2p in HFIP,
we also tried DCM and MeCN as solvents for the reaction. However,
product 2p was obtained in 58 and 70% yield, respectively.
(17) The formation of iodobenzene was detected by comparative
TLC analysis in each reaction run in Table 2.
(9) For papers describing the construction of heterocyles via N−N
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(18) Hajos
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