Palladium-catalyzed ortho-alkoxylation of 2-aryl-1,2,3-triazoles

Article abstract of DOI:10.1021/jo5008306

Palladium-catalyzed alkoxylation of 2-aryl-1,2,3-triazoles was described in the presence of various groups in the aromatic rings. In addition, some other directing groups of heterocycles containing nitrogen were explored.

Full text of DOI:10.1021/jo5008306

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Article
Palladium-Catalyzed Ortho-Alkoxylation of 2-Aryl-1,2,3-Triazoles
Suping Shi, and Chunxiang Kuang
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 10 Jun 2014
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PalladiumꢀCatalyzed OrthoꢀAlkoxylation of 2ꢀArylꢀ1,2,3ꢀTriazoles
Suping Shi and Chunxiang Kuang*
7
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9
Department of Chemistry, Tongji University, Siping Road 1239, Shanghai 200092, China, and
Key Laboratory of Yangtze River Water Environment, Ministry of Education, Shanghai 200092,
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China
Fax: +86ꢀ21ꢀ65983191; Eꢀmail: kuangcx@tongji.edu.cn.
R2
R2
N
N
N
N
N
N
Pd(OAc)2,K2S2O8
OR
H
ROH
+
R1
°
CF3COOH, DCE, 80 C, 24h
R1
24 examples
up to 82% yield
°
°
1 & 2 alcohol
Palladiumꢀcatalyzed alkoxylation of 2ꢀarylꢀ1,2,3ꢀtriazoles was described in the presence of
various groups in the aromatic rings. In additiaon, some other directing groups of heterocycles
containing nitrogen were explored.
INTRODUCTION
Transitionꢀmetalꢀcatalyzed C–H functionalization has become a highly efficient and applicable
method for the synthesis of natural and unnatural compounds.1 However, the development of metalꢀ
catalyzed methods for direct conversion of C–H bond into C–O bond remains a tremendous challenge
in elaborating complex organic structure,2 because of the electronegativity of the oxygen element as
well as the metalꢀligand bond strength.3 As important structural motifs, ethers are omnipresent in
complex and biologically active compounds.4 Traditionally, ethers are formed via acidꢀcatalyzed
condensation of alcohols, coupling of alkoxides and alkyl halides (Williamson synthesis), and
alkoxymercuration/demercuration of alkenes. More recently, various strategies for the synthesis of aryl
alkyl ethers have been reported.5,6 All of these strategies are appealing, but each one has its
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shortcomings, such as limited substrate range, multiꢀstep reaction, significant formation of byproducts,
and so on. Therefore, developing novel method for the preparation of ethers become an important and
challenging task. Sanford7 and Yu8 have reported palladiumꢀcatalyzed directed orthoꢀalkoxylation of
the C(sp2)–H bonds, and these works addressed some of the challenges. Despite the achievement of C–
H oxygenation,9 C–H alkoxylation still reactions remain relatively scarce.
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1,2,3ꢀtriazole, due to its special chemical and medicinal properties, has been widely applied in
pharmaceutical , bulk, and fine chemical industries over the past decades.10 Recently, we have reported
the orthoꢀacylation and halogenation of 2ꢀarylꢀ1,2,3ꢀtriazoles.11 Motivated by our interest in the C–H
bond activation, we explore C–H functionalization with the assistance of 1,2,3ꢀtriazole. Herein, we
describe an efficient and selective method for the palladiumꢀcatalyzed alkoxylation of 2ꢀarylꢀ1,2,3ꢀ
triazole at the ortho-position of the N2ꢀarene using alcohols as alkoxylated reagents.
RESULTS AND DISCUSSION
Alcohols can be used as solvent in palladiumꢀcatalyzed C–H bond functionalization.7a,7b,9c,12
Therefore, we performed the reaction of 2ꢀphenylꢀ1,2,3ꢀtriazole 1a with 10 mol% of Pd(OAc)2 and 4
equiv of K2S2O8 in methanol placed in a sealed tube, as shown in Table 1. To our delight, the
desired compound 3a was identified with a 45% yield after stirring for 24 h at 80 °C (Entry 1). The
alkoxylation did not proceed at all in the absence of palladium catalyst. The reduction of palladium(II)
by the alcohol solvent lead to the irreversible formation of palladium black.7b,9c To improve the yield,
we reduced the amount of methanol to 25 equiv and added other solvents including dioxane, 1,2ꢀ
dichloroethane (DCE), N,Nꢀdimethylformamide (DMF), acetonitrile, dichloromethane (DCM) and pꢀ
xylene (Entry 2ꢀ7). DCE gave the best result among these common solvents to afford 55% yield (Entry
3). However, when 10 equiv methanol was used in DCE, the yield was reduced to 43% (Entry 8).
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Table 1. Optimization of Alkoxylation Reaction Conditionsa
4
5
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8
N
N
N
N
N
N
Pd(OAc) 2, additive
oxidant, solvent
OMe
+
MeOH
2a
9
1a
3a
10
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12
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alcohol
(equiv)
additive
(equiv)
oxidant
(equiv)
yield
(%)
entry
solvent
45
40
0
0
1
methanol K2S2O8 (4.0)
dioxane
2
3
4
25
K2S2O8 (4.0)
DCE
K2S2O8 (4.0)
0
0
55
25
25
DMF
K2S2O8 (4.0)
K2S2O8 (4.0)
K2S2O8 (4.0)
K2S2O8 (4.0)
K2S2O8 (4.0)
PhI(OAc)2 (4.0)
TBHP (4.0)
trace
5
CH3CN
DCM
trace
42
0
0
0
0
25
25
6
7
34
p-xylene
DCE
25
10
25
8
9
43
35
DCE
0
0
0
10
DCE
25
25
10
trace
11
12
13
O2(1 atm)
DCE
DCE
0
Cu(OAc)2 (4.0)
K2S2O8 (4.0)
25
25
25
trace
67
DCE
CF3COOH(0.5)
45
DCE
DCE
DCE
DCE
K2S2O8 (4.0)
CF3SO3H(0.5)
14
K2S2O8 (4.0)
K2S2O8 (4.0)
K2S2O8 (4.0)
15
CH3SO3H(0.5)
CF3COOH(0.5)
25
38
16c
25
25
25
23
52
54
17d
(0.5)
CF3COOH
K2S2O8 (4.0)
K2S2O8 (4.0)
CF3COOH(1.0)
18
19
DCE
DCE
CF3COOH(0.2)
25
62
a Reaction conditions: 1a (0.3 mmol), Pd(OAc)2 (10 mol%), oxidant (1.2 mmol)
and solvent(2.0 mL) at 80 C for 24 h. b Yield of isolated product. c The
°
reactions were carried out at 100 °C for 24 h. d The reactions were carried out
°
at 60 C for 24h.
Changing the oxidant to PhI(OAc)2, tertꢀbutyl hydroperoxide (TBHP), O2 (1 atm) and Cu(OAc)2, we
found these oxidants were substantially less effective (Entry 9ꢀ12). In the previous studies, some
additives brought important effects on CꢀH bond activation reaction. When 0.5 equiv of CF3COOH was
added, the yield was improved to 67% (Entry 13). Nevertheless, the stronger organic acids CH3SO3H
and CF3SO3H, which have significant effects on palladiumꢀcatalyzed C–H bond activation reaction,13
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failed to improve the yield under our catalytic conditions (Entries 14 and 15). However, the yield was
not improved, even we adjusted the temperature (Entries 16 and 17). Similarly, the yield was still not
improved when 1.0 equiv or 0.2 equiv of CF3COOH were added, respectively (Entry 18 and 19).
With the optimal conditions in hand (Table 1, entry 13), we then explored other 2ꢀarylꢀ1,2,3ꢀ
triazole 1 and alcohol 2 to examine the scope of the current reaction, as shown in Table 2. A variety of
2ꢀarylꢀ1,2,3ꢀtriazoles could be coupled with primary and secondary alcohols, and for most cases, the
alkoxylated products were obtained in moderate yields. The results generally showed that substrates
with electronꢀdonating groups gave higher yield than those with electronꢀwithdrawing groups (Entries
2ꢀ7). Furthermore, functional groups such as aryl halide, ester, ether and ketone were tolerated under
the oxidizing reaction conditions. Subsrates with a meta-substituent on the phenyl ring was more
efficient than those with a paraꢀsubstituent (Entry 8 vs 4). Other primary alcohols, including EtOH, nꢀ
BuOH and HO(CH2)2OH, were applied to afford the correspondly alkoxylated products with 39% to
67% yields (Entries 10ꢀ13). The results indicated that alcohols with linear chains gave high yields
(Entry 1 vs 10, 12). It was worth noting that for the 2ꢀ(naphthalenꢀ1ꢀyl)ꢀ1,2,3ꢀtriazole, methoxylation
occurred on 8ꢀposition instead of the 2ꢀposition (Entry 9). The reason may be that a cyclopalladated
intermediate formed with the carbon atom on 8ꢀposition is more stable than on 2ꢀposition. Ortho-
substitution on phenyl rings is known to hinder the orthoꢀC–H bond insertions in Palladiumꢀcatalyzed
C–H activation.14 However, the subsrate with orthoꢀMe substituent did not display the “orthoꢀ
substituent” effect, and in contrast, gave a high yield (Entries 2, 11, 15). This phenomenon also occured
in other C–H funtionalization,9a and the exact reason is still unclear. Moreover, the secondary alcohol iꢀ
PrOH could aslo react with a variety of 2ꢀarylꢀ1,2,3ꢀtriazoles in yield of 52%ꢀ82% (Entries 14ꢀ17).
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Table 2. Direct Alkoxylation of 1,2,3ꢀTriazolea
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6
7
Pd(OAc)2 (10 mol%)
TFA (0.5 equiv)
N
N
N
N
N
N
+
ROH
R
K2S2O8, DCE
80 °C, 24h
R
RO
1
2
3
8
9
Product (
)
Yield of 3 (%)b
1
Entry
1
ROH (2)
3
N
N
N
MeOH
65
N
N
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1a
2a
N
3a
MeO
N
N
N
N
N
MeOH
77
62
N
N
2
3
3b
1b
N
2a
MeO
N
N
MeOH
N
O
O
N
N
2a
1c
3c
MeO
N
MeOH
57
4
5
N
N
COOMe
N
COOMe
2a
N
N
1d
MeO
N
3d
Cl
N
N
N
N
MeOH
54
Cl
2a
MeO
3e
1e
N
N
N
N
MeOH
45
58
6
7
8
N
N
N
N
CF3
CF3
2a
1f
3f
MeO
N
N
O
O
N
MeOH
N
1g
N
2a
3g
MeO
N
N
COOMe
N
MeOH
68
N
2a
3h
COOMe
1h
N
MeO
N
N
N
MeOH
9
N
75
61
67
N
N
2a
3i
3j
1i
MeO
N
N
N
N
N
EtOH
10
N
N
2b
1a
1b
1a
EtO
N
N
N
N
N
N
EtOH
2b
11
N
3k
3l
EtO
N
N
n-BuOH
N
N
39
44
12
13
2c
n-BuO
N
N
HO(CH2)2OH
N
N
N
2d
3m
3n
1a
N
N
HO(H2C)2O
N
N
N
N
N
i-PrOH
14
15
64
82
1a
2e
i-PrO
N
N
N
N
i-PrOH
2e
N
3o
3p
1b
N
i-PrO
N
N
i-PrOH
N
N
O
60
52
16
17
N
N
O
2e
N
i-PrO
1c
N
N
N
N
N
i-PrOH
Cl
Cl
2e
1e
3q
3r
i-PrO
N
N
N
N
N
c-PenOHc
71
N
N
18
19
2f
1j
c-PenO
N
N
N
N
N
c-HexOHc
2g
3s
74
35
1b
c-HexO
N
N
N
N
N
3t
1a
Benzyl alcohold
20
N
2h
Bz O
a Reaction conditions: 1a (0.5 mmol), alcohol (12.5 mmol), Pd(OAc)2 (10 mol%), K2S2O8
(2 mmol), CF3COOH(0.5 equiv) in DCE (3.0 mL) at 80 °C for 24h.b Yield of isolated product.
c 10 equiv of alcohol was used. d 5 equiv of alcohol was used.
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When other secondary alcohols such as cyclopentanol and cyclohexanol were used, the alkoxylation
could also proceed smoothly with 71% and 74% yield, respectively (Entries 18 and 19). Benzyl alcohol
can be employed to gave corresponding product with a low yield of 38% with the generation of
benzaldehyde (Entry 20). However, the reaction did not take place when tꢀBuOH and phenol were used.
It was noted that none or trace dialkoxylated product was observed under the reaction conditions. The
reason for the low yields of some products was that the starting material could not be consumed
completely even after longer reaction time.
10
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Table 3. Direct Alkoxylation of Further SubstitutedTriazole Units a
Pd(OAc)2 (10 mol%)
TFA (0.5 equiv)
N
N
N
N
R
N
R
N
+
ROH
K2S2O8, DCE
80 °C, 24h
MeO
1
2
3
Entry
3
Product ( )
1
ROH (2)
Yield of 3 (%)b
OHC
N
N
N
38
1c
OHC
MeOH
2a
3ua
N
MeO
N
1k
OMe
N
OMe
N
HO
N
40
N
3ub
MeO
MeOOC
MeOOC
N
2
3
N
N
MeOH
2a
N
N
1l
60
N
3v
MeO
N
N
N
N
N
N
MeOH
2a
1m
1m
3w
62
58
MeO
N
N
N
N
i-PrOH
2e
4
3x
N
N
i-PrO
N
MeOH
2a
no
N
5
6
N
N
MeOH
2a
N
no
N
a Reaction conditions: 1a (0.5 mmol), alcohol (12.5 mmol), Pd(OAc)2 (10 mol%),
K2S2O8(2 mmol),TFA(0.5 equiv) in DCE (3.0 mL) at 80 °C for 24h.b Yield of isolated
product. c No TFA was used.
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Inspired by the promising results above, we then focused on the directing effect of further
substituted triazole units. We performed the reactions of 2ꢀphenylꢀ1,2,3ꢀtriazoles bearing substitution
on the heteroarene, i.e., ꢀCHO (1k), –COOMe (1l) and phenyl (1m) with MeOH and iꢀPrOH in Table 3.
The results generally showed that the electronic property of the substituents on the heteroarene of 2ꢀ
aryꢀ1,2,3ꢀtriazoles had no obvious effect on the reaction efficiency (Entries 2 and 3). Substrate 1k gave
the alkoxylated product accompanied by the generation of 3ub due to the chemical activity of
aldehyde (Entry 1). However, when 2ꢀethylꢀ1,2,3ꢀtriazole and 2ꢀethylꢀ1,2,3ꢀbenzotriazole were used,
10
11
12
13
14
15
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17
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no alkoxylated products were observed (Entries 5 and 6).
Table 4. Different Directing Groupsa
N
N
N
Pd(OAc)2 (10 mol%)
OMe
MeO
OMe
+
MeOH
or
K2S2O8, DCE
80 °C, 24h
4
2a
4
5
b
Entry
5
2
Product ( )
5
Yield of (%)
MeOH ( )
Ν
N
O
MeOH
2a
88%
1
4a
4b
4c
O
5a
N
N
O
N
O
MeOH
N
45%
2
2a
5b
MeO
N
N
N
N
MeOH
2a
3
HO
OMe
42%
5c
Ο
NH
Ν
MeOH
2a
4
none
4d
a Reaction conditions: 1a (0.5 mmol), alcohol (12.5 mmol), Pd(OAc)2 (10 mol%), K2S2O8
(2 mmol) in DCE (3.0 mL) at 80 °C for 24h.b Yield of isolated product. c The reaction
temperatureo was 105 °C.
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With the optimized conditions in hand, we investigated the directing effect of other heterocycle
containing nitrogen in Table 4. For pyridine as the directing group, the dimethoxylated product was
obtainded with a 80% yield after 24 h (Entry 1). While for pyrazolone, monomethoxylated product was
identified with a lower yield of 45% under identical reaction condition (Entry 2). Interesting, for
pyrazole, when the reaction temperature was improved to 105 °C, alkoxylation and hydroxylation both
took place (Entry 3). However, other directing group 4d failed to gave the alkoxylated products (entry
4). The reacton conditions were compatible to these chemically active functional groups, which
enhanced its practicability in synthesis.
10
11
12
13
14
15
16
17
18
19
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23
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Next, to obtain insight into the reaction mechanism, we conducted kinetic isotope effect (KIE)
studies (Scheme 1). As shown in Scheme 1, the KIE was observed to be 3.3, indicating that the C–H
bond cleavage at the orthoꢀposition of 2ꢀarylꢀ1,2,3ꢀtriazole is most likely involved with the rateꢀ
limiting step. We performed additional experiments without K2S2O8. In this reaction, 1a (1 equiv.),
Pd(OAc)2 (1 equiv.) and DCE (3 mL) were added in the tube. The reaction mixture was stirred for 10 h,
leading the formation of potential intermediate A. Then MeOH was added in the tube. After 20 h, we
did not find 3a (Scheme 2). Therefore we can conclude that the mechanism possibily involve a
palladium(II)/palladium(IV) pathway in this alkoxylation reaction, but not the palladium(II)/
palladium(0) pathway.
Scheme 1. Intermolecular Kinetic Isotope Effect
MeOH
Pd(OAc)2 (10 mol%)
TFA (0.5 equiv)
N
N
N
N
N
N
N
N
N
D
N
N
N
+
OMe
D
D
OMe
D
+
D
D
D
D
K2S2O8, DCE
80 °C, 24h
D
-
3a
1a [D ]
1a
-
4
1a [D ]
5
:
1
3.3
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Scheme 2. Formation of Palladacycle A and Attempted Formation of 3a
5
6
7
8
9
Pd(OAc)2
MeOH
N
N
N
N
N
N
(1 equiv)
X (25 equiv)
N
N
N
Pd
X
OMe
DCE, 120 °C
10
11
12
13
14
15
16
17
18
19
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A
1a
3a
Although the details of the mechanism of this alkoxylation reaction remain to be elucidated, a
possible is outlined based on earlier literature7,8,9,15 and our preliminary studies(Scheme 3). First, the
coordination of nitrogen atom in 1,2,3ꢀtriazole 1 with palladium(II) species triggers cyclopalladation to
form intermediate A. Next, palladium(II) intermediate was oxidized to palladium(IV) intermediate B
by K2S2O816, which then undergoes ligand exchange to form C. Reductive elimination of C gives the
alkoxylated product 3 accompanied by the regeneration of palladium(II) catalyst. There may be another
pathway for the formation of intermediate A because the 2ꢀ(1,2,3ꢀtriazole) group is a strong electronꢀ
donating group.17 The first step involves the chelation of palladium with nitrogen atom in 1,2,3ꢀ
triazole, followed by the intramolecular electronic rearrangement. After two rearrangements,
intermediate A is formed. However, the metaꢀEWGꢀsubstituted substrate, which does not form
resonance structure, gave a better yield (Tabble 2, entry 8). It should be noted that the bimetallic
palladium(II))/palladium(III) pathway could not be excluded.18
Scheme 3. Possible Mechanism for the PdꢀCatalyzed Alkoxylation Reaction
N
N
N
N
N
N
N
N
X
N
N
X
X
X
N
N
N
N
N
Pd OR
Pd
Pd
X
[O]
Pd(II)
-Pd(II)
RE
ROH
-HX
OR
X
B
A
N
C
or
X
+
N
N
N
N Pd
:
X
N
Pd
X
H
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In conclusion, we have described the direct alkoxylation of 2ꢀarylꢀ1,2,3ꢀtriazole with primary and
secondary alcohols. The reaction exhibited broad functional group tolerance and was complementary to
the previous methods for the synthesis of 1,2,3ꢀtriazole derivatives. Some other directing groups of
heterocycles containing nitrogen were explored. Further investigations on the mechanism are still in
progress.
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Experimental Section
General Information
All commercially available reagents and solvent were obtained from the commercial providers and
used without further purification. 2ꢀarylꢀ1,2,3ꢀtriazoles 1 were prepared according to known
procedures19
.
General procedure for the synthesis of 2ꢀarylꢀ1,2,3ꢀtriazoles:
A reaction mixture containing aryl halide (1.0 eq.), 1,2,3ꢀtriazole (1.2 eq.), CuO (0.1 eq.), Fe(acac)3
(0.3 eq.), Cs2CO3 (2 eq.) was stirred in DMF in a flask at 100 °C for 24 h under air. After cooling to
room temperature, the mixture was diluted with ethyl acetate and washed with water. Organic layers
were gathered, dried over Na2SO4, filtered and concentrated in vacuum to yield the crude product. The
resulting residue was purified on silica gel chromatography to give the starting materials.
General procedure for the alkoxylation of 2ꢀsubstituted 1,2,3ꢀtriazoles: A mixture of 2ꢀsubstituted
1,2,3ꢀTriazole 1 (0.5 mmol), alcohol 2 (12.5 mmol), Pd(OAc)2 (0.05 mmol), K2S2O8(2 mmol) and
CF3COOH (0.5 equiv) in DCE (3.0 mL) was stirred at 80 °C for 24h in sealed tube. The mixture was
diluted with CH2Cl2 (15 mL) and washed with water (10 mL). The organic phase was dried over
anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was
purified by using a preparative silica gel TLC to give the products 3.
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Determination of intermolecular kinetic isotope effect: MeOH (400mg, 12.5 mmol) was added to an
ovenꢀdried, sealed tube charged with 2ꢀphenylꢀ2Hꢀ1,2,3ꢀtriazole (1a) (36 mg, 0.25 mmol), 2ꢀphenylꢀ
d5ꢀ2Hꢀ1,2,3ꢀtriazole (1aꢀd5) (38 mg, 0.25 mmol), Pd(OAc)2 (11mg, 0.05 mmol), TFA (28mg, 0.25
mmol) and K2S2O8 (538 mg, 2 mmol) in DCE (3 mL). The reaction mixture was stirred at 80ºC for 24
h. The mixture was cooled to room temperature. The mixture was diluted with CH2Cl2 (15 mL) and
filtered. The solvent was then evaporated under vacuum. The resulting residue was purified by using a
preparative silica gel TLC to yield product. The ratio of 3a / 3aꢀ[D4] was determined to be 2.00 / 0.61
(KIE = 3.3) by 1H NMR spectroscopy.
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Compounds 5a20 has been previously reported, and its identities were confirmed by comparison of their
spectral data with reported ones.
2ꢀphenylꢀ2Hꢀ1,2,3ꢀtriazole (1a)11b : 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 7.8 Hz, 2H), 7.84 (s,
2H), 7.51 (t, J = 7.9 Hz, 2H), 7.38 (t, J = 7.4 Hz, 1H).
2ꢀphenylꢀd5ꢀ2Hꢀ1,2,3ꢀtriazole (1aꢀd5): 1H NMR (400 MHz, CDCl3) δ 7.82 (s, 2H).
2ꢀoꢀtolylꢀ2Hꢀ1,2,3ꢀtriazole (1b)21: 1H NMR (400 MHz, CDCl3) δ 7.83 (s, 2H), 7.55 (d, J = 6.9 Hz, 1H),
7.37 – 7.28 (m, 3H), 2.35 (s, 3H).
2ꢀ(4ꢀmethoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (1c)11b: 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 9.1 Hz,
2H), 7.77 (s, 2H), 6.99 (d, J = 9.1 Hz, 2H), 3.85 (s, 3H).
Methyl 4ꢀ(2Hꢀ1,2,3ꢀtriazolꢀ2ꢀyl)benzoate (1d)22: 1H NMR (400 MHz, CDCl3) δ 8.22ꢀ8.13 (m, 4H),
7.86 (s, 2H), 3.95 (s, 3H).
2ꢀ(4ꢀchlorophenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (1e)11a: 1H NMR (400MHz, CDCl3) δ 8.03 (d, J = 8.9 Hz, 2H),
7.81 (s, 2H), 7.45 (d, J = 8.9 Hz, 2H).
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2ꢀ(4ꢀ(trifluoromethyl)phenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (1f)11a: 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J =
8.5 Hz, 2H), 7.85 (s, 2H), 7.75 (d, J = 8.6 Hz, 2H).
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1ꢀ(4ꢀ(2Hꢀ1,2,3ꢀtriazolꢀ2ꢀyl)phenyl)ethanone (1g)11b: 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.8
Hz, 2H), 8.08 (d, J = 8.8 Hz, 2H), 7.85 (s, 2H), 2.63 (s, 3H).
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Methyl 3ꢀ(2Hꢀ1,2,3ꢀtriazoleꢀ2ꢀyl)benzoate (1h)11b: 1H NMR (400 MHz, CDCl3) δ 8.78 (s, 1H), 8.31
(dd, J = 8.1, 1.1 Hz, 1H), 8.06 (d, J = 7.8 Hz, 1H), 7.87 (s, 2H), 7.60 (t, J = 8.0 Hz, 1H), 3.99 (s, 3H).
2ꢀ(1ꢀnaphthaleneyl)ꢀ2Hꢀ1,2,3ꢀtriazole (1i)11b: 1H NMR (400 MHz, CDCl3) δ 8.15 (dd, J = 6.2, 3.4 Hz,
1H), 8.05ꢀ7.93 (m, 4H), 7.82 (d, J = 7.4 Hz, 1H), 7.64 – 7.52 (m, 3H).
2ꢀpꢀtolylꢀ2Hꢀ1,2,3ꢀtriazole (1j) 11b: 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.5 Hz, 2H), 7.82 (s,
2H), 7.28 (d, 2H), 2.43 (s, 3H).
2ꢀphenylꢀ2Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarbaldehyde (1k)23: 1H NMR (400 MHz, CDCl3) δ 10.24 (s, 1H), 8.29
(s, 1H), 8.16 (d, J = 7.8 Hz, 2H), 7.56 (t, J = 7.6 Hz,2H), 7.47 (t, J = 7.1 Hz, 1H).
methyl 2ꢀphenylꢀ2Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (1l) 23: 1H NMR (400 MHz, CDCl3) δ 8.24 (s, 1H),
8.14 (d, J = 7.8 Hz, 2H), 7.51 (t, J = 7.8 Hz, 2H), 7.42 (t, J = 7.4 Hz, 1H), 4.00 (s, 3H).
2ꢀphenylꢀ2Hꢀbenzo[d][1,2,3]triazole (1m)19: 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 7.7 Hz,
2H), 7.94 (dd, J = 6.6, 3.1 Hz, 2H), 7.57 (t, J = 7.8 Hz, 2H), 7.50 – 7.39 (m,3H).
2ꢀ(2ꢀmethoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3a): According to the General Procedure, a crude product
was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.30) to give 3a (58.6 mg,
66 %) as a yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.85 (s, 2H), 7.52 (d, J = 7.7 Hz, 1H), 7.43 (t,
J = 7.9 Hz, 1H), 7.12ꢀ7.01 (m, 2H), 3.86 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 153.5, 135.1, 130.4,
129.8, 127.1, 120.7, 112.8, 56.3. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C9H9N3O: 175.0746;
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found: 175.0743. IR:max(thin film) (cm ꢀ1) = 3409, 3237, 3010, 2982, 2876, 2362, 1513, 1450, 1412,
1308.
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2ꢀ(2ꢀmethoxyꢀ6ꢀmethylphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3b): According to the General Procedure, a crude
product was purified by using a preparative silica gel TLC (Hex/EA = 8/1, Rf =0.35) to give 3b (72.8
mg, 77 %) as a yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.84 (s, 2H), 7.32 (t, J = 8.0 Hz, 1H), 6.86
(m, 2H), 3.71 (s, 3H), 1.95 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 155.7, 137.8, 134.9, 130.7, 129.2,
122.4, 109.5, 56.0, 17.0. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C10H11N3O: 189.0902; found:
189.0906. IR:max(thin film) (cm ꢀ1) = 3415, 3299, 2962, 2939, 2841,2360, 2342, 1687, 1604, 1590,
1495,1356
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2ꢀ(2,4ꢀdimethoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3c): According to the General Procedure, a crude
product was purified by using a preparative silica gel TLC (Hex/EA = 4/1, Rf =0.41) to give 3c (63.5
1
mg, 62 %) as a white solid, mp 62.4ꢀ62.9 °C. H NMR (400 MHz, CDCl3) δ 7.81 (s, 2H), 7.40 (d, J =
8.7 Hz, 1H), 6.60 (s, 1H), 6.55 (d, J = 8.7Hz, 1H), 3.86 (s, 3H), 3.82 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 161.4, 154.8, 134.9, 127.9, 123.5, 104.4, 99.8, 56.2, 55.6. HRMS (ESIꢀTOF): m/z [M + Na+]
calcd for C10H11N3O2: 205.0851; found: 205.0856. IR:max(thin film) (cm ꢀ1) = 3473, 3416, 3409, 2922,
2847, 2359, 2341, 1616, 1558, 1472, 1457.
methyl 3ꢀmethoxyꢀ4ꢀ(2Hꢀ1,2,3ꢀtriazolꢀ2ꢀyl)benzoate (3d): According to the General Procedure, a
crude product was purified by using a preparative silica gel TLC (Hex/EA = 4/1 , Rf =0.32) to give 3d
1
(66.4 mg, 57 %) as a white solid, mp 74.6ꢀ75.1 °C. H NMR (400 MHz, CDCl3) δ 7.88 (s, 2H), 7.83ꢀ
7.77 (m, 2H), 7.66 (d, J = 8.1 Hz, 1H), 4.03ꢀ3.93 (m, 6H). 13C NMR (101 MHz, CDCl3) δ 166.1, 152.9,
135.7, 133.0, 131.6, 126.5, 122.1, 114.0, 56.6, 52.5. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for
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C11H11N3O3: 233.0800; found: 233.0802. IR:max(thin film) (cm ꢀ1) = 3564, 3235, 2920, 2849, 2359,
2341, 2065, 1717, 1637, 1616, 1457,1237.
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2ꢀ(4ꢀchloroꢀ2ꢀmethoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3e): According to the General Procedure, a crude
product was purified by using a preparative silica gel TLC (Hex/EA = 10/1 , Rf =0.45) to give 3e (56.4
mg, 54 %) as a yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.85 (s, 2H), 7.47 (d, J = 8.3 Hz, 1H), 7.10
– 7.02 (m, 2H), 3.87 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 153.9, 135.9, 135.42, 128.4, 127.8, 120.8,
113.4, 56.6. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C9H8ClN3O: 209.0356; found: 209.0359.
IR:max(thin film) (cm ꢀ1) = 3564, 3482, 3416, 3237, 2929, 2872, 2360, 2341, 1616, 1507, 1456.
2ꢀ(2ꢀmethoxyꢀ4ꢀ(trifluoromethyl)phenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3f): According to the General
Procedure, a crude product was purified by using a preparative silica gel TLC (Hex/EA = 4/1 , Rf
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=0.48) to give 3f (54.8 mg, 45 %) as a white solid, mp 73.3ꢀ73.9 °C. H NMR (400 MHz, CDCl3) δ
7.89 (s, 2H), 7.70 (d, J = 8.2 Hz, 1H), 7.35 (d, J = 8.3 Hz, 1H), 7.32 (s, 1H), 3.95 (s, 3H). 13C NMR
(101 MHz, CDCl3) δ 153.3, 135.8, 132.2, 132.2 (q, J = 32.7 Hz), 127.2, 123.5 (q, J = 271 Hz), 117.7 (q,
J = 3.9 Hz), 110.0 (q, J = 3.7 Hz), 56.6. 19F NMR (377 MHz, CDCl3) δ ꢀ62.7. HRMS (ESIꢀTOF): m/z
[M + Na+] calcd for C10H8F3N3O: 243.0619; found: 243.0621. IR:max(thin film) (cm ꢀ1) =3496, 3464,
3404, 3025, 2921, 2864, 2331, 1638, 1617, 1491.
1ꢀ(3ꢀmethoxyꢀ4ꢀ(2Hꢀ1,2,3ꢀtriazolꢀ2ꢀyl)phenyl)ethanone (3g): According to the General Procedure, a
crude product was purified by using a preparative silica gel TLC (Hex/EA = 4/1 , Rf =0.25) to give 3g
1
(62.9 mg, 58 %) as a white solid, mp56.7ꢀ61.2°C. H NMR (400 MHz, CDCl3) δ 7.87 (s, 2H), 7.71 –
7.65 (m, 2H), 7.62 (d, J = 8.1, 1H), 3.94 (s, 3H), 2.63 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 196.8,
153.2, 138.3, 135.7, 133.1, 126.6, 121.3, 112.1, 56.6, 26.7. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for
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C11H11N3O2: 217.0851; found: 217.0848. IR:max(thin film) (cm ꢀ1) =3461, 3437, 3230, 2962, 2877, 2360,
2339, 1702, 1616, 1501,1334,1240.
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methyl 4ꢀmethoxyꢀ3ꢀ(2Hꢀ1,2,3ꢀtriazolꢀ2ꢀyl)benzoate (3h): According to the General Procedure, a
crude product was purified by using a preparative silica gel TLC (Hex/EA = 6/1 , Rf =0.41) to give 3h
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(79.2 mg, 68 %) as a white solid, mp 67.9ꢀ68.2 °C. H NMR (400 MHz, CDCl3) δ 8.23 (s, 1H), 8.15 (d,
J = 8.7, 1H), 7.88 (s, 2H), 7.13 (d, J = 8.7 Hz, 1H), 3.94 (s, 3H), 3.90 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 165.8, 157.0, 135.4, 132.2, 129.4, 128.7, 122.9, 112.1, 56.5, 52.2. HRMS (ESIꢀTOF): m/z [M
+ Na+] calcd for C11H11N3O3: 233.0800; found: 233.0803. IR:max(thin film) (cm ꢀ1) =3454, 3469, 3417,
2953, 2920, 2850, 2360, 2341, 1717, 1615, 1516,1363, 1269.
2ꢀ(8ꢀmethoxynaphthalenꢀ1ꢀyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3i): According to the General Procedure, a crude
product was purified by using a preparative silica gel TLC (Hex/EA = 10/1 , Rf =0.30) to give 3i (84.4
mg, 75 %) as a brown solid, mp 83.8ꢀ84.5°C. 1H NMR (400 MHz, CDCl3) δ 7.97 (dd, J = 7.7, 1.6 Hz,
1H), 7.84 (s, 2H), 7.54 (t, J = 5.2 Hz, 1H), 7.52ꢀ7.48 (m, 2H), 7.43 (t, J = 8.0 Hz, 1H), 6.83 (d, J = 7.7
Hz, 1H), 3.53 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 155.0, 136.1, 135.9, 134.0, 130.6, 127.0, 126.3,
125.2, 121.5, 120.7, 107.1, 56.3. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C13H11N3O: 225.0902;
found: 225.0906. IR:max(thin film) (cm ꢀ1) =3473, 3417, 3234, 2958, 2932, 2838, 2360, 2341, 1652,
1636, 1616, 1404, 1260.
2ꢀ(2ꢀethoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3j): According to the General Procedure, a crude product was
purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.37) to give 3j (57.6 mg, 61 %) as
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a yellow liquid. H NMR (400 MHz, CDCl3) δ 7.83 (s, 2H), 7.49 (d, J = 7.8, Hz, 1H), 7.43ꢀ7.38 (m,
1H), 7.13ꢀ7.00 (m, 2H), 4.09 (q, J = 7.0 Hz, 2H), 1.31 (t, J = 7.0 Hz, 3H). 13C NMR (101 MHz, CDCl3)
δ 153.2, 135.0, 130.4, 127.2, 120.6, 114.2, 65.0, 14.6. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for
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C10H11N3O: 189.0902; found: 189.0907. IR:max(thin film) (cm ꢀ1) =3648, 3566, 2981, 2927, 2851, 2359,
2341, 1600, 1506, 1456, 1412, 1286.
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2ꢀ(2ꢀethoxyꢀ6ꢀmethylphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3k): According to the General Procedure, a crude
product was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.38) to give 3k
(68.0mg, 67 %) as a yellow solid, mp 46.0ꢀ46.4°C. 1H NMR (400 MHz, CDCl3) δ 7.84 (s, 2H), 7.30 (t,
J = 8.0 Hz, 1H), 6.91 – 6.81 (m, 2H), 3.97 (q, J = 7.0 Hz, 2H), 1.97 (s, 3H), 1.19 (t, J = 7.0 Hz, 3H).
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13C NMR (101 MHz, CDCl3) δ 155.2, 137.7, 134.7, 130.5, 129.6, 122.2, 110.8, 64.6, 17.0, 14.5. HRMS
ꢀ1
(ESIꢀTOF): m/z [M + Na+] calcd for C11H13N3O: 203.1059; found: 203.1062. IR:max(thin film) (cm
=3481, 2978, 2929, 2872, 2359, 1605, 1589, 1491, 1475, 1414, 1373.
)
2ꢀ(2ꢀbutoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3l): According to the General Procedure, a crude product was
purified by using a preparative silica gel TLC (Hex/EA = 20/1, Rf =0.29) to give 3l (42.3mg, 39 %) as
a yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.83 (s, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.41 (t, J = 7.2 Hz,
1H), 7.10ꢀ7.00 (m, 2H), 4.01 (t, J = 6.5 Hz, 2H), 1.72 – 1.61 (m, 2H), 1.34ꢀ1.29 (m, 2H), 0.87 (t, J =
7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 153.4, 134.9, 130.4, 130.3, 127.1, 120.5, 114.1, 69.1, 31.0,
19.0, 13.7. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C12H15N3O: 217.1215; found: 217.1217.
IR:max(thin film) (cm ꢀ1) =3457, 3010, 2924, 2851, 2358, 2341, 1601, 1505, 1457, 1484, 1410, 1371,
1263.
2ꢀ(2ꢀ(2Hꢀ1,2,3ꢀtriazolꢀ2ꢀyl)phenoxy)ethanol (3m): According to the General Procedure, a crude
product was purified by using a preparative silica gel TLC (Hex/EA = 2/1, Rf =0.31) to give 3m
1
(45.1mg, 44 %) as a yellow liquid. H NMR (400 MHz, CDCl3) δ 7.86 (s, 2H), 7.67 – 7.60 (m, 1H),
7.40 (t, J = 8.6 Hz, 1H), 7.16 – 7.09 (m, 2H), 4.30 (t, J = 8.0 Hz, 2H), 3.86 (t, J = 8.0 Hz, 2H). 13C
NMR (101 MHz, CDCl3) δ 152.0, 135.2, 130.5, 130.0, 126.1, 121.9, 116.5, 72.7, 61.0. HRMS (ESIꢀ
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TOF): m/z [M + Na+] calcd for C10H11N3O2: 205.0851; found: 205.0847. IR:max(thin film) (cm
=3469, 3408, 2925, 2874, 2359, 1601, 1506, 1455, 1416, 1357, 1289, 1252.
)
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2ꢀ(2ꢀisopropoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3n): According to the General Procedure, a crude product
was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.39) to give 3n (68.0mg,
67 %) as a yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.82 (s, 2H), 7.48 (d, J = 7.8 Hz, 1H), 7.39 (t,
J = 8.0 Hz, 1H), 7.10 (d, J = 8.1 Hz, 1H), 7.05 (t, J = 7.7 Hz, 1H), 4.49 – 4.38 (m, 1H), 1.23 (d, J = 6.1
Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 152.5, 134.9, 131. 6, 130.3, 127.3, 120.9, 116.9, 72.6, 22.0.
HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C11H13N3O: 203.1059; found: 203.1056. IR:max(thin film)
(cm ꢀ1) =3551, 3475, 3408, 3235, 2978, 2920, 2849, 2359, 2341, 1652, 1637, 1616, 1558, 1505.
2ꢀ(2ꢀisopropoxyꢀ6ꢀmethylphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3o): According to the General Procedure, a
crude product was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.35) to give
3o(92.2mg, 82 %) as a yellow solid, mp 39.3ꢀ41.0 °C. 1H NMR (400 MHz, CDCl3) δ 7.83 (s, 2H), 7.29
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(t, J = 8.0 Hz, 1H), 6.93ꢀ6.82 (m, 2H), 4.46 – 4.35 (m, 1H), 1.96 (s, 3H), 1.15 (d, J = 6.1 Hz, 6H). 13
C
NMR (101 MHz, CDCl3) δ 154.5, 137.8, 134.6, 130.9, 130.4, 122.4, 113.0, 72.0, 21.9, 17.1. HRMS
ꢀ1
(ESIꢀTOF): m/z [M + Na+] calcd for C12H15N3O: 217.1215; found: 217.1220. IR:max(thin film) (cm
=3481, 2978, 2929, 2872, 2359, 1605, 1589, 1491, 1475, 1414, 1373.
)
2ꢀ(2ꢀisopropoxyꢀ4ꢀmethoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3p): According to the General Procedure, a
crude product was purified by using a preparative silica gel TLC (Hex/EA = 4/1, Rf =0.39) to give
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3p(69.9mg, 60 %) as a yellow liquid. H NMR (400 MHz, CDCl3) δ 7.79 (s, 2H), 7.36 (d, J = 8.7 Hz,
1H), 6.61 (s, 1H), 6.56 (d, J = 8.7Hz, 1H), 4.45 – 4.34 (m, 1H), 3.84 (s, 3H), 1.22 (d, J = 6.1 Hz, 6H).
13C NMR (101 MHz, CDCl3) δ 161.2, 153.7, 134.7, 128.0, 125.2, 105.1, 103.2, 72.5, 55.6, 21.9. HRMS
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ꢀ1
(ESIꢀTOF): m/z [M + Na+] calcd for C12H15N3O2: 233.1164; found: 233.1158. IR:max(thin film) (cm
=3367, 2982, 2848, 2360, 2341, 2065, 1683, 1637, 1616, 1519, 1457, 1315.
)
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2ꢀ(4ꢀchloroꢀ2ꢀisopropoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3q): According to the General Procedure, a
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crude product was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.39) to give
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3q(61.6mg, 52 %) as a yellow liquid. H NMR (400 MHz, CDCl3) δ 7.82 (s, 2H), 7.42 (d, J = 8.4 Hz,
1H), 7.07 (s, 1H), 7.03 (d, J = 8.4 Hz, 1H), 4.52ꢀ4.41 (m, 1H), 1.26 (d, J = 6.1 Hz, 6H). 13C NMR (101
MHz, CDCl3) δ 153.0, 135.7, 135.2, 129.9, 128.1, 120.9, 116.7, 72.9, 21.8. HRMS (ESIꢀTOF): m/z [M
+ Na+] calcd for C11H12ClN3O: 237.0669; found: 237.066. IR:max(thin film) (cm ꢀ1) =3480, 3471, 3239,
2980, 2921, 2850, 2359, 2341, 1652, 1636, 1617, 1558, 1500.
2ꢀ(2ꢀ(cyclopentyloxy)ꢀ4ꢀmethylphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3r): According to the General Procedure,
a crude product was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.41) to give
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3r(86.3mg, 71 %) as a yellow liquid. H NMR (400 MHz, CDCl3) δ 7.79 (s, 2H), 7.33 (d, J = 8.0 Hz,
1H), 6.87 (s, 1H), 6.83 (d, J = 8.1 Hz, 1H), 4.77 – 4.71 (m, 1H), 2.40 (s, 3H), 1.77 (m, 4H), 1.66 – 1.43
(m, 4H). 13C NMR (101 MHz, CDCl3) δ 152.4, 140.6, 134.7, 128.8, 126.9, 121.0, 116.4, 81.0, 32.7,
23.6, 21.7. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C14H17N3O: 243.1372; found: 243.1375.
IR:max(thin film) (cm ꢀ1) = 3478, 3329, 2970, 2913, 2839, 1621, 1614, 1491, 1435, 1421, 1373, 1254,
1223.
2ꢀ(2ꢀ(cyclohexyloxy)ꢀ6ꢀmethylphenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3s): According to the General Procedure, a
crude product was purified by using a preparative silica gel TLC (Hex/EA = 15/1, Rf =0.35) to give
3s(100.2mg, 78 %) as a pale yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.84 (s, 2H), 7.30 (t, J = 8.0
Hz, 1H), 6.91ꢀ6.84 (m, 2H), 4.26 – 4.17 (m, 1H), 1.99 (s, 3H), 1.64 – 1.18 (m, 10H). 13C NMR (101
MHz, CDCl3) δ 154.3, 137.7, 134.5, 130.8, 130.4, 122.2, 112.9, 76.2, 31.2, 25.5, 22.9, 17.1. HRMS
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ꢀ1
(ESIꢀTOF): m/z [M + Na+] calcd for C15H19N3O: 257.1528; found: 257.1530. IR:max(thin film) (cm
=3456, 3369, 2984, 2925, 2864, 1626, 1610, 1502, 1446, 1435, 1421, 1373, 1254, 1223.
)
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2ꢀ(2ꢀ(benzyloxy)phenyl)ꢀ2Hꢀ1,2,3ꢀtriazole (3t): According to the General Procedure, a crude product
was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.37) to give 3t (43.9mg, 35%)
as a yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.86 (s, 2H), 7.55 (d, J = 7.8 Hz, 1H), 7.42 – 7.27 (m,
6H), 7.09 (m, 2H), 5.15 (s, 2H). 13C NMR (101 MHz, CDCl3) δ 152.7, 136.5, 135.1, 130.6, 130.3,
128.4, 127.8, 127.2, 126.8, 121.2, 115.0, 71.0. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C15H13N3O:
251.1059; found: 251.1056. IR:max(thin film) (cm ꢀ1) = 3478, 3416, 3405, 3109, 3020, 2991, 2923, 1691,
1473,1385, 955
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2ꢀ(2ꢀmethoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarbaldehyde (3ua): According to the General Procedure,
a crude product was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.45) to give
3ua (38.6 mg, 38 %) as pale yellow solid. mp. 87.6 ꢀ 88.2 °C 1H NMR (400 MHz, CDCl3) δ 10.23 (s,
1H), 8.30 (s, 1H), 7.61 – 7.45 (m, 2H), 7.17 – 7.06 (m, 2H), 3.89 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ 184.4, 153.6, 147.8, 135.0, 131.4, 129.1, 127.0, 120.7, 112.9, 56.3. HRMS (ESIꢀTOF): m/z [M + Na+]
calcd for C10H9N3O2: 203.0695; found: 203.0698. IR:max(thin film) (cm ꢀ1) = 3489, 3459, 3412, 3127,
3061, 2918, 2842, 1618, 1507, 1249,1025
dimethoxy(2ꢀ(2ꢀmethoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazolꢀ4ꢀyl)methanol (3ub): According to the General
Procedure, a crude product was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf
=0.31) to give 3ub (53.0 mg, 40 %) as a white solid. mp. 132.2 ꢀ 132.6 °C. 1H NMR (400 MHz, CDCl3)
δ 7.86 (s, 1H), 7.50 (d, J = 7.8 Hz, 1H), 7.45 – 7.38 (m, 1H), 7.08 – 7.00 (m, 2H), 5.68 (s, 1H), 3.83 (s,
3H), 3.42 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 153.63, 146.77, 133.81, 130.53, 129.67, 127.16,
120.55, 112.66, 98.22, 56.21, 53.06. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C12H15N3O4:
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265.1063; found: 265.1068. IR:max(thin film) (cm ꢀ1) = 3554, 3489, 3408, 3231, 3124, 3025, 2923, 2854,
1704, 1611, 1485, 1451, 1309
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methyl 2ꢀ(2ꢀmethoxyphenyl)ꢀ2Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (3v): According to the General
Procedure, a crude product was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf
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=0.34) to give 3v (69.9 mg, 60%) as a yellow solid, mp. 67.5 ꢀ 68.1°C. H NMR (400 MHz, CDCl3) δ
8.29 (s, 1H), 7.53 (d, J = 7.7, 1H), 7.50 – 7.43 (m, 1H), 7.11 – 7.03 (m, 2H), 3.98 (s, 3H), 3.85 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 161.2, 153.7, 140.6, 137.5, 131.3, 129.2, 127.3, 120.6, 112.6, 56.2, 52.4
HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C11H11N3O3: 233.0080; found: 233.0085. IR:max(thin film)
(cm ꢀ1) = 3557, 3420, 3412, 3380, 3127, 2923, 2901, 1726, 1383, 1117.
2ꢀ(2ꢀmethoxyphenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (3w): According to the General Procedure, a crude
product was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.37) to give 3w (69.8
1
mg, 62%) as a yellow liquid. H NMR (400 MHz, CDCl3) δ 7.97 (dd, J = 6.6, 3.1 Hz, 2H), 7.66 (dd, J
= 7.8, 1.4 Hz, 1H), 7.53 – 7.47 (m, 1H), 7.43 (dd, J = 6.6, 3.1 Hz, 2H), 7.20 – 7.07 (m, 2H), 3.87 (s,
3H). 13C NMR (101 MHz, CDCl3) δ 153.7, 144.9, 131.2, 130.3, 127. 7, 126.8, 120.7, 118.5, 112.8, 56.4.
HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C13H11N3O: 225.0902; found: 225.0905. IR:max(thin film)
(cm ꢀ1) = 3423, 3234, 2984，2896，2365, 1652, 1488, 1442, 1372, 1285, 1153.
2ꢀ(2ꢀisopropoxyphenyl)ꢀ2Hꢀbenzo[d][1,2,3]triazole (3x): According to the General Procedure, a
crude product was purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.41) to give 3x
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(73.3 mg, 58%) as a yellow liquid. H NMR (400 MHz, CDCl3) δ 7.97 (dd, J = 6.6, 3.0 Hz, 2H), 7.62
(d, J = 7.8 Hz, 1H), 7.49 – 7.42 (m, 3H), 7.21 – 7.06 (m, 2H), 4.53 – 4.41 (m, 1H), 1.22 (d, J = 6.1 Hz,
6H). 13C NMR (101 MHz, CDCl3) δ 152.5, 144.7, 132.1, 130.9, 127.8, 126.6, 121.0, 118.5, 117.0, 72.8,
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22.0. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C15H15N3O: 253.1215; found: 253.1211. IR:max(thin
film) (cm ꢀ1) = 3411, 3227, 3165, 2934, 2864, 1546, 1485, 1423, 1354, 1233, 1186, 1079
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2ꢀ(2,6ꢀdimethoxyphenyl)pyridine (5a)20: According to the General Procedure, a crude product was
purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.32 ) to give 5a (94.6mg, 88 %) as
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a white solid. H NMR (400 MHz, CDCl3) δ 8.73 (d, J = 4.5 Hz, 1H), 7.72 (td, J = 7.7, 1.7 Hz, 1H),
7.36 – 7.28 (m, 2H), 7.23 (dd, J = 6.9, 5.5 Hz, 1H), 6.65 (d, J = 8.4 Hz, 2H), 3.73 (s, 6H). 13C NMR
(101 MHz, CDCl3) δ 158.1, 154.5, 149.2, 135.8, 129.7, 126.3, 121.7, 119.0, 104.2, 56.0.
2ꢀ(2ꢀmethoxyphenyl)ꢀ1,5ꢀdimethylꢀ1Hꢀpyrazolꢀ3(2H)ꢀone (5b): According to the General Procedure,
a crude product was purified by using a preparative silica gel TLC (EA/MeOH = 20/1, Rf =0.45) to
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give 5b (70.8mg, 65 %) as a yellow solid, mp 101.2ꢀ101.7 °C. H NMR (400 MHz, CDCl3) δ 7.44 –
7.37 (m, 1H), 7.30 (d, J = 7.7Hz, 1H), 7.08 ꢀ 7.00 (m, 2H), 5.34 (s, 1H), 3.82 (s, 3H), 3.04 (s, 3H), 2.21
(s, 3H). 13C NMR (101 MHz, CDCl3) δ 166.1, 156. 6, 151.5, 131.3, 131.1, 123.1, 121.1, 112.7, 95.6,
56.1, 33.2, 12.7. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C12H14N2O2: 218.1126; found: 218.1135.
IR:max(thin film) (cm ꢀ1) =3002, 2823, 1629, 1565, 1552, 1530, 1483, 1452, 1384.
3ꢀmethoxyꢀ2ꢀ(1Hꢀpyrazolꢀ1ꢀyl)phenol (5c): According to the General Procedure, a crude product was
purified by using a preparative silica gel TLC (Hex/EA = 10/1, Rf =0.34) to give 5c (39.9mg, 42 %) as
a yellow liquid. 1H NMR (400 MHz, CDCl3) δ 11.00 (s, 1H), 8.29 (d, J = 2.2 Hz, 1H), 7.75 (s, 1H),
7.15 (t, J = 8.3 Hz, 1H), 6.77 (d, J = 8.3 Hz, 1H), 6.59 (d, J = 8.3 Hz, 1H), 6.506 – 6.458 (m, 1H), 3.92
(s, 3H). 13C NMR (101 MHz, CDCl3) δ 151.5, 151.2, 138.4, 132.9, 127.6, 116.0, 111.3, 105.6, 103.1,
56.1. HRMS (ESIꢀTOF): m/z [M + Na+] calcd for C10H10N2O2: 190.0742 ; found: 190.0747.
IR: max (thin film) (cm ꢀ1) =3543, 3378, 3217, 3102, 2827, 1564, 1527, 1522, 1483, 1419, 1374.
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Intermediate A: To a stirred solution of 2ꢀphenylꢀ2Hꢀ1,2,3ꢀtriazole (1a) (73 mg, 0.5 mmol), Pd(OAc)2
(112 mg, 0.5 mmol) in DCE (3 mL) at 120ºC for 2 h. The solid was collected and washed with EtOAc
to give Intermediate A (118mg, 93%) as a black solid. 1H NMR (400 MHz, CDCl3) δ 7.21 (s, 1H), 7.14
(d, J = 7.8 Hz, 1H), 7.10 (s, 1H), 7.06 – 7.00 (m, 1H), 6.95 (d, J = 3.8 Hz, 2H), 2.30 (s, 3H). 13C NMR
(101 MHz, CDCl3) δ 182.5, 141.0, 134.1, 133.4, 131.7, 129.4, 126.6, 125.2, 113.6, 24.5
Acknowledgment. Financial support was provided by the National Natural Science Foundation of
China (No. 21272174) and the Key Projects of Shanghai in Biomedicine (No.08431902700). We also
thank the Center for Instrumental Analysis, Tongji University, China.
ASSOCIATED CONTENT
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Supporting Information Available.
Copies of NMR spectra of products 1aꢀ1m, 3a−x, 5aꢀc and intermediate A. This material is available
free of charge via the Internet at http://pubs.acs. org.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: kuangcx@tongji.edu.cn.
ACKNOWLEDGMENTS
Financial support was provided by the National Natural Science Foundation of China (No. 21272174) and the Key
Projects of Shanghai in Biomedicine (No.08431902700). We also thank the Center for Instrumental Analysis,
Tongji University, China
.
Reference
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Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 10539. (c) Vorogushin, A. V.; Huang, X.; Buchwald, S. L. J. Am.
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Chem. Soc. 2005, 127, 8146. (d) Gowrisankar, S.; Sergeev, A. G.; Anbarasan,P.; Spannenberg, A.; Neumann, H.;
Beller, M. J. J. Am. Chem. Soc. 2010, 132, 11592. (e) Wu, X.; Fors, B. P.; Buchwald, S. L. AngewChem., Int. Ed.
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H.; Yu, J.ꢀQ. Angew. Chem., Int. Ed., 2009, 48, 5094
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