Bifunctional Phosphine Ligand-Enabled Gold(I)-Catalyzed O-Nucleophilic Addition of N-Hydroxybenzo[1,2,3]-triazin-4(3 H)-ones to Alkynes Followed by [3,3]-Rearrangement: Simultaneous Formation of C-O and C-N Bonds

Article abstract of DOI:10.1021/acs.joc.0c00471

We describe a gold (I)-catalyzed tandem O-nucleophilic addition/[3,3]-rearrangement reaction of N-hydroxybenzo[1,2,3]-triazin-4(3H)-ones with alkynes enabled by a biphenyl-2-yl phosphine ligand featuring a pendant amide moiety (L1). A variety of 1-(2-oxo-2-arylethyl)benzo [d][1,2,3]triazin-4(1H)-one derivatives were synthesized in good to excellent yields. The present protocol gives a rare example of simultaneous formation of C-O and C-N bonds in the gold(I)-catalyzed [3,3]-sigmatropic rearrangements.

Full text of DOI:10.1021/acs.joc.0c00471

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Article
Bifunctional Phosphine Ligand-Enabled Gold(I)-Catalyzed O-Nucleophilic
Addition of N-Hydroxybenzo[1,2,3]-triazin-4(3H)-ones to Alkynes Followed
by [3,3]-Rearrangement: Simultaneous Formation of C-O and C-N Bonds
Yongcai Xu, Kanghe Zheng, Bingwei Zhou, Hongwei Jin, and Yunkui Liu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00471 • Publication Date (Web): 21 Apr 2020
Downloaded from pubs.acs.org on April 21, 2020
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Bifunctional Phosphine Ligand-Enabled Gold(I)-Catalyzed O-Nucleophilic
Addition of N-Hydroxybenzo[1,2,3]-triazin-4(3H)-ones to Alkynes Followed by
[3,3]-Rearrangement: Simultaneous Formation of C-O and C-N Bonds
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Yongcai Xu,§ Kanghe Zheng,§ Bingwei Zhou, Hongwei Jin,* and Yunkui Liu*
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, College of Chemical
Engineering, Zhejiang University of Technology, Hangzhou 310014, People’s Republic of China
E-mail: ykuiliu@zjut.edu.cn; jhwei828@zjut.edu.cn
TOC graphic
O
O
N
O
H
R2
L1
AuNTf2 (1 mol %)
N
N
R1
R2
N
+
N
DCM, 80 C, 4 h
N
R1
R2
O
O
N
N
26 examples
O
N
(up to 98% yield!)
R1
isolable
intermediate
ABSTRACT
We describe a gold(I)-catalyzed tandem O-nucleophilic addition/[3,3]-rearrangement reaction of
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N-hydroxybenzo[1,2,3]-triazin-4(3H)-ones with alkynes enabled by a biphenyl-2-yl phosphine ligand
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featuring
a
pendant
amide
moiety
(L1).
A
variety
of
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1-(2-oxo-2-arylethyl)benzo[d][1,2,3]triazin-4(1H)-one derivatives were synthesized in good to
excellent yields. The present protocol gives a rare example of simultaneous formation of C-O and C-N
bonds in the gold(I)-catalyzed [3,3]-sigmatropic rearrangements.
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Introduction
Benzo[1,2,3]triazin-4-one derivatives represent an important class of nitrogen-containing
heterocyclic compounds whose scaffold is often found in a broad spetrum of pharmaceutical,
agrochemical, and biologically active molecules1 and may exhibit a range of pharmacological
properties such as sedative,2 diuretic,3 anesthetic,4 antiarthritic,5 antitubercular6 and antitumor
activities.7 Besides, they are also widely used as synthetic intermediates due to their unique
reactivities.8 Among researches on the synthesis of benzo[1,2,3]triazin-4-one derivatives,2-7,9,10
currently, most efforts have been devoted to synthesize those N3-substituted ones;2-7,9 while in
sharp constrast, only few reports have been documented on the construction of N1-substituted ones
possibly due to the difficulty to access this kind of compounds.10 In view of their potential
utilizations in pharmaceutical, agrochemical and organic chemistry, it is thus highly desirable to
develop efficient methods to access N1-substituted benzo[1,2,3]triazin-4-one derivatives.
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In the past two decades, homogeneous gold catalysis has received considerable attention in
organic synthesis and become a useful and powerful tool for the construction of carbon-carbon or
carbon-heteroatom bonds.11 The attractiveness of homogeneous gold catalysts in organic synthesis
lies in their versatile catalytic capacities such as Lewis acid catalyst, -activator, and/or initiator of
carbenoid intermediates, etc. Thus, the combination of gold catalyst as the most strong soft-Lewis
acid in activating carbon-carbon multiple bonds for nucleophile addition and gold catalyst as Lewis
acid in promoting [3,3]-sigmatropic rearrangement12 can provide an efficient and useful strategy
for the construction of a variety of complex molecules which are usually difficult to be accessed by
other transition metal catalysts (Scheme 1a).13 For example, in 2005, Zhang group reported a
gold(I)-catalyzed highly efficient synthesis of cyclopentenones from enynyl esters involving
tandem [3,3]-rearrangement and Nazarov reaction.13a Later, the same group also realized efficient
syntheses of 2-alkylindoles from N-arylhydroxyamine derivatives and alkynes involving gold(I)- or
gold(I)/zinc-catalyzed tandem O-nucleophilic addition/[3,3]-rearrangement/cyclodehydration
sequence.13b,c In 2009, Asensio group reported a gold(I)-catalyzed intermolecular oxyarylation of
alkynes involving O-nucleophilic addition of sulfoxides to alkynes followed by [3,3]-sigmatropic
rearrangement.13d In 2013, an intramolecular version of oxyarylation of alkynes in the
gold(I)-catalyzed transformations of alkynyl aryl sulfoxides with the similar mechanism as
Asensio’s work was reported by Zhang et al.13e In the same year, Hashmi et al realized a
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gold(I)-catalyzed
tandem
cyclization/[3,3]-sigmatropic
rearrangement
of
allyl-(ortho-alkinylphenyl)-methyl ethers to afford allylated isochromenes with excellent yields and
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selectivity.13f Although there is a wealth of work in the gold-catalyzed tandem nucleophilic
addition/[3,3]-sigmatropic rearrangement reactions, most of these studies focused on the
simultaneous construction of C-C and C-O bonds;13 to the best of our knowledge, no examples for
the simultaneous formation of C-O and C-N bonds in the gold-catalyzed [3,3]-rearrangement step
have been reported. In 2012, Xu13g and co-workers reported a gold(I)-catalyzed addition of
hydroxybenzotriazole dervatives to alkynes where [3,3]-rearrangement selectively led to the
simultaneous formation of C-C and C-O bonds rather than C-O and C-N bonds (Scheme 1b). In
2015, Mo10c et al realized the simultaneous formation of C-O and C-N bonds through O-arylation
and [3,3]-rearrangement in the reaction of N-hydroxybenzo[1,2,3]-triazin-4(3H)-ones and
diaryliodonium salts (Scheme 1c). Inspired by Xu’s and Mo’s work, we envisioned that
gold-catalyzed reaction of N-hydroxybenzo[1,2,3]-triazin-4(3H)-ones with alkynes might allow for
the simultaneous formation of C-O and C-N bonds via an O-nucleophilic
addition/[3,3]-rearrangement sequence, thus leading to the convenient synthesis of N1-substituted
benzo[1,2,3]triazin-4-one derivatives (Scheme 1d). As our ongoing interest in coinage
metal-catalyzed tandem reactions,14 herein we would like to describe our fulfillment of this idea
where a biphenyl-2-ylphosphine ligand featuring a critical remote amide group (WangPhos, L1)15
was found to be crucial for achieving high effectiveness of gold(I) catalysis.
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Scheme 1. Gold-catalyzed tandem nucleophilic addition/[3,3]-rearrangement reactions
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a) gold-catalyzed tandem nucleophilic addition/[3,3]-rearrangement reactions
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B
Y
3
A
X
B
1
nucleophilic
addition
LAu+ as
Y
B A
Y
A
2
[3,3]-rearrangement
complex
molecules
X
X
1
LAu+ as
3
further
transformations
2
LAu+
-activator

Lewis acid
b) gold-catalyzed tandem nucleophilic addition/[3,3]-rearrangement reactions of hydroxybenzotriazoles and alkynes:
simultaneous formation of C-C/C-O bonds rather than C-O/C-N bonds
O
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R

R
2
O
N
N
3
formation of
R1
N
O
N
N
H
1
C-C/C-O bonds
N
H
3
LAu+
2
1
+
R1
R1
R
N
2
N
N
N
3
R1
N

formation of
C-O/C-N bonds
N
O
R
c) tandem O-arylation/[3,3]-rearrangement reaction of N-hydroxybenzo[1,2,3]-triazin-4(3H)-ones and diaryliodonium salts:
simultaneous formation of C-O/C-N bonds
O
O
O
N
N
O
H
O
Ar
R
N
N
N
N
[3,3]-rearrangement
R
R
+ Ar2IOTf
N
formation of
C-O/C-N bonds
N
N
O
H
R1
d) gold-catalyzed tandem nucleophilic addition/[3,3]-rearrangement reactions of N-hydroxybenzo[1,2,3]-triazin-4(3H)-ones
and alkynes: simultaneous formation of C-O/C-N bonds
O
Ad
R2
O
Ad
O
P
formation of
N
N
O
H
R2
N
N
C-O/C-N bonds
L1
AuNTf2 (1 mol %)
R2
N
N
+
R1
N
O
N
[3,3]-rearrangement
DCM, 80 C, 4 h
N
R1
N
R1
O
O
L1
WangPhos (
)
Results and Discussion
To test our idea, initially, 3-hydroxybenzo[1,2,3]triazin-4(3H)-one 1a and phenylacetylene 2a
were selected as the model substrates to investigate the optimal reaction conditions (Table 1).
Reaction of 1a and 2a in dichloromethane (DCM) catalyzed by a commonly used Ph3PAuNTf2 (1
mol %) at 80 °C for 4 h indeed delivered the desired product N1-substituted benzo[1,2,3]triazin-4-one
derivative 3aa, albeit in a very low yield and most of the starting materials were recovered (3aa: 8%;
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entry 1, Table 1). With NHC-ligand-coordinated gold(I) cationic catalysts, the yield of 3aa was still
low (entries 2, 3, Table 1). We then switched to investigate a bifunctional ligand WangPhos (L1) which
was designed by Zhang group.15a This ligand was derived from the privileged biphenyl-2-ylphosphine16
framework with a critical remote amide group at the C3ʹ position, which was able to significantly
accelerate the addition of HNu (e. g. carboxylic acid or in situ generated hydrazoic acid) across alkynes
and dramatically lower the gold catalyst loading, mechanistically through cooperative role between
gold activating alkynes and amide group activating HNu.15a,b Gratifyingly, a significantly improved
yield of 3aa was indeed achieved when 1 mol % of WangPhos-Au(I)NTf2 was used as the catalyst
(98% yield, entry 4, Table 1). Note that WangPhos performed much better than Ad-JohnPhos (L2,
entry 5, Table 1), indicating that the ligand remote amide group might engage accelerating interaction
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-
with 1a. Other counterions were investigated, and it was found that BF4 gave almost equal result as
-
-
that of NTf2 while OTf- and SbF6 gave inferior results (entries 6-8 vs 4, Table 1). Solvent screening
experiments indicated that DCM was the most suitable choice of the reaction medium (entries 9-12 vs
4, Table 1). Lowering the catalyst loading (0.5 mol %) and temperature (60 °C) only led to reduced
yields of 3aa (entries 13, 14, Table 1). Control experiments showed that gold(I) catalyst was
indispensable for the reaction, while only the starting materials were recovered quantitatively in the
absence of L1AuNTf2 (entry 15, Table 1).
Table 1. Optimization of reaction conditions.a
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O
N
O
N
N
N
OH
LAuX (1 mol %)
N
N
+
solvent, under N2
temp, 4 h
9
O
1a
2a
3aa
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entry
1
catalyst (mol %)
Ph3PAuNTf2 (1)
IMesAuNTf2 (1)
IPrAuNTf2 (1)
L1AuNTf2 (1)
L2AuNTf2 (1)
L1AuBF4 (1)
L1AuOTf (1)
L1AuSbF6 (1)
L1AuNTf2 (1)
L1AuNTf2 (1)
L1AuNTf2 (1)
L1AuNTf2 (1)
L1AuNTf2 (0.5)
L1AuNTf2 (1)
--
solvent
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
THF
temp
80
80
80
80
80
80
80
80
80
80
80
80
80
60
80
yield (%)b
8
6
2
3
29
98
66
96
89
81
25
56
trace
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47
38
0
4
5
6
7
8
9
10
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12
13
14
15
toluene
DMF
MeCN
DCM
DCM
DCM
aReaction conditions: 1a (0.2 mmol), 2a (0.24 mmol, 1.2 equiv based on 1a), catalyst (1 mol % based
on 1a), and solvent (1.0 mL) were stirred in a sealed Schrenk bottle under N2 atmosphere at given
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b
temperature for 4 h unless otherwise noted. Optimized conditions are shown in bold. Isolated yield.
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cOnly the starting materials were recovered almost quantitatively.
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PAd2
1'
2'
PAd2
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N
3'
O
WangPhos (L1)
Ad-JohnPhos (L2)
With the optimized reaction conditions in hand, we next examined the substrate scope of alkynes 2
(Table 2). At first, terminal aryl alkynes were investigated. A range of aryl alkynes containing either
electron-rich or electron-deficient aryl rings underwent the nucleophilic addition/3,3-rearrangement
smoothly and afforded the desired product 3 in good to excellent yields (3ab-3am, Table 2). Generally,
alkynes 2 containing electron-donating groups delivered higher yields of products than those
possessing electron-withdrawing ones (3ab, 3ac, 3ae, 3af, 3ah, 3ai, 3al, 3am vs 3ad, 3ag, 3ak, Table
2). It seemed that the position of substituents on the aryl rings (ortho-, meta- or para-) had no
significant impact on the outcome of the reaction in terms of reaction times and yields (3ab vs 3ae vs
3ah, 3af vs 3ai, Table 2). The reaction of 2-ethynylnaphthalene with 1a underwent well under the
standard reaction conditions and gave the target product in 94% yield (3an, Table 2). Substates
containing heteroaryl groups such as 2-pyridinyl and 2-thiophenyl were viable under the standard
reaction conditions, and the corresponding N1-substituted benzo[1,2,3]triazin-4-one derivatives were
obtained in 82% and 88% yield, respectively (3ao and 3ap, Table 2). Next, the reaction of 1a with
aliphatic terminal alkynes were investigated. To our delight, aliphatic terminal alkynes also participated
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the reaction smoothly and delivered the desired products in good to excellent yields (3aq, 3ar, 3at, 3au,
Table 2) except in the case of 3as in a lower yield of 33% due to a lower conversion of the starting
materials. To obtain satisfactory yields, in several cases (e. g. 3ak, 3ap, 3as, 3au, Table 2), higher
temperatures (100 °C) and/or longer reaction times (6 h) were required. Unfortunately, internal alkynes
were inert substrates for the present transformation (not listed in Table 2).
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Table 2. Substrate scope of alkynes 2.a
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O
N
O
N
N
N
L1AuNTf2 (1 mol %)
OH
N
N
R1
+
DCM, under N2
80 °C, 4 h
R1
8
9
2
O
1a
3
O
N
O
N
O
O
N
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N
N
N
N
N
N
N
N
N
O
N
O
Cl
O
: 95%
O
: 91%
3ae
3ab
3ac
: 96%
3ad
: 82%
O
O
O
O
N
N
N
N
N
N
N
N
N
OMe
N
N
N
OMe
Br
O
O
O
O
: 96%
O
3ag
: 76%
3af
3ai
: 96%
3ah
: 93%
O
O
O
N
N
N
N
N
N
N
N
N
CO2Me
Ph
N
N
N
O
: 90%
O
bO
O
3aj
: 95%
3ak
: 78%
3am
3al
: 90%
O
O
O
N
O
N
N
N
N
N
N
N
N
N
N
N
S
N
O
O
O
O
c
3ap
: 88%
3aq
3an
: 97%
: 94%
3ao
: 82%
O
O
O
O
N
N
N
N
N
N
N
N
N
N
N
N
Cl
O
O
O
O
b
b
3ar
3at
: 98%
: 95%
3as
: 33%
3au
: 83%
aReaction conditions: 1 (0.2 mmol), 2 (0.24 mmol, 1.2 equiv based on 1), L1AuNTf2 (1 mol % based
on 1), and DCM (1.0 mL) were stirred in a sealed Schrenk bottle under N2 atmosphere at 80 °C for 4 h
unless otherwise noted. bThe temperature is 100 °C. cThe reaction was conducted at 100 °C for 6 h.
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The substrate scope of 3-hydroxybenzo[1,2,3]triazin-4(3H)-ones 1 was further examined (Table
3). A range of 3-hydroxybenzo[1,2,3]triazin-4(3H)-ones 1 with substituents at the C6-, C7-, or
C8-position could react with 2a smoothly under the standard reaction conditions and afforded the
desired products in good to excellent yields (3aa-3fa, Table 3). It was found that the electronic property
and the site of substituents had no significant impact on the reaction outcome in terms of reaction times
and product yields (3ba, 3da vs 3ea, Table 3).
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Table 3. Substrate scope of 3-hydroxybenz[1,2,3]triazin-4(3H)-one.a
O
O
N
5
3
4
R2
6
R2
7
OH
L1AuNTf2 (1 mol %)
N
N
N
+
N
DCM, under N2
80 °C, 4 h
2
N
1
8
O
1
2a
3
O
N
O
N
O
H
Me
Cl
N
N
N
N
N
N
N
O
O
O
3aa
3ba
3ca
: 92%
: 98%
: 97%
O
O
O
N
N
N
N
N
N
N
Me
N
Me
N
Me
Me
O
O
O
3da
3ea
3fa
: 97%
: 93%
: 98%
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aReaction conditions: 1 (0.2 mmol), 2 (0.24 mmol, 1.2 equiv based on 1), L1AuNTf2 (1 mol % based
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on 1), and DCM (1.0 mL) were stirred in a sealed Schrenk bottle under N2 atmosphere at 80 °C for 4 h
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unless otherwise noted.
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To further demonstrate the synthetic potential of the present methodology, a 1 mmol-scale synthesis
of 3aa was also tried, and the target N1-substituted benzo[1,2,3]triazin-4-one derivatives 3aa was
obtained in 97% yield (eq.(1)).
O
O
N
L1AuNTf2 (1 mol %)
OH
N
eq. (1)
N
N
N
+
DCM, under N2
80 C, 28 h
N
O
1a
2a
3aa
(1.0 mmol)
0.16 g
(1.2 mmol)
0.12 g
0.26 g: 97%
To gain insight into the mechanism of the reaction, we tried to isolate the reaction intermediate
(Scheme 2). When running the reaction of 1a and 2a under the standard reaction conditions except at
10 °C for 24 h, the nucleophilic addition product 4 could indeed be isolable (35% yield, (eq.(2),
Scheme 2). Furthermore, subjection of 4 to the standard reaction conditions afforded 3aa almost
quantitatively (eq.(3), Scheme 2), strongly supporting that the 3,3-rearrangement step arised from
intermediate 4. It seemed that the gold(I) catalyst is not indispensable for the 3,3-rearrangement of 4
since the reaction still gave 3aa in 84% yield in the absence of the gold(I) catalyst (eq.(3), Scheme 2).
Scheme 2. Mechanistic experiments
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O
O
O
N
L1AuNTf2 (1 mol %)
OH
N
N
eq. (2)
N
N
N
+
DCM, under N2
10 C, 24 h
8
9
1a
2a
4
(35%)
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O
O
with or without
L1AuNTf2 (1 mol %)
N
N
N
O
N
N
eq. (3)
N
DCM, under N2
80 C, 4 h
4
O
3aa
with L1AuNTf2: 99% yield
without L1AuNTf2: 84% yield
On the basis of the mechanistic experiments and previous literature,10c,11c,13g,15 a possible reaction
mechanism for the formation of 3aa is proposed in Scheme 3. According to Zhang’s work,15
a
quasi-intramolecular nucleophilic addition mechanism involving cooperative role between gold
activating alkyne and basic amide group activating HNu might account for the enhancement of the
catalytic activity of L1AuNTf2. Alternatively, since Ad-JohnPhos without a basic amide group also
delivered the desired product 3aa in 66% yield (see entry 5, Table 1, vide supra), thus a traditional
gold-catalyzed intermolecular nucleophilic addition mechanism could not be excluded.11c,13g We
speculate that the final [3,3]-sigmatropic rearrangement may proceed via an intramolecular concerted
process with or without a gold(I) catalyst.10c
Scheme 3. Proposed mechanism
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O
N
N
4
5
6
7
8
9
Quasi-intramolecular nucleophilic addition mechanism
involving cooperative role between gold activating alkyne
and basic amide group activating HNu
N
Ph
3aa
O
Ad
Ad
O
10
11
12
13
14
15
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P
O
H
with or without
gold(I) catalyst
N
N
3,3-rearrangement
Au
Ph
+
N
2a
1a
O
O
N
N
N
O
N
4
O
Ad
Ph
Ad
N
X:
P
Au
Ad
Ad
Ph
P
O
X:
Au
Ad
H
O
Ad
Ph
N
N
H
H
O
P
+
A
N
O
Au
N
N
X
H
Ph
O
N
C
O
H
N
X
N
B
N
Traditional intermolecular nucleophilic addition mechanism:
O
O
O
with or without
L1Au+
O
H
N
N
N
N
protondeauration
L1Au+
+
O
N
4
N
N
H
3aa
O
N
N
3,3-rearrangement
Ph
Ph
Ph
L1Au+
L1Au
Conclusion
In summary, a simultaneous formation of C-O and C-N bonds in the gold(I)-catalyzed tandem
nucleophilic addition/3,3-rearrangement reaction of N-hydroxybenzo[1,2,3]-triazin-4(3H)-ones with
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alkynes has been successfully achieved, thus leading to the synthesis of N1-substituted
benzo[1,2,3]triazin-4-one derivatives in good to excellent yields. The rational design of a
biphenyl-2-ylphosphine ligand (L1) featuring a critical remote amide moiety is a key factor for
achieving high effectiveness of the gold(I) catalyst.
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Experimental Section
Unless otherwise stated, all reagents were purchased from commercial suppliers and used without
1
13
purification. The H and C NMR spectra were recorded on a spectrometer at 25 C in CDCl3 or
DMSO-d6 at 500 MHz and 126 MHz, respectively. Proton chemical shifts (δ) are relative to
13
tetramethylsilane (TMS, δ = 0.00) as internal standard and expressed in ppm. Chemical shifts of C
NMR were reported relative to the solvent signal (CDCl3: δ = 77.16 ppm; DMSO-d6: δ = 39.51 ppm).
GC-MS experiments were performed with an Agilent 6890N GC system equipped with a 5973N
mass-selective detector with EI source; High resolution mass spectra (HRMS) were obtained on a TOF
MS instrument with EI or ESI source. Flash column chromatography was performed on silica gel
(100-200 mesh) with the indicated solvent mixtures.
All the alkynes are commercially available and used without purification. The WangPhos (L1) and
L1AuNTf2 were prepared according to Zhang’s work.15a
General Procedure for the Synthesis of Substrate 1.
General procedure.10c,17,18 To a suspension of substituted 2-amino-N-hydroxybenzamides18 (5
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mmol) in water (5 mL) was added concentrated HCl (2 mL) with stirring. While the mixture cooled in
an ice bath, a cold solution of NaNO2 (0.69 g, 10 mmol) in water (5 mL) was added dropwise, and the
temperature was maintained below 0 °C. The mixture was further stirred in the ice bath for another 30
min, and the solid was filtered, washed with a small amount of cold water, and dried to give product 1.
All the analytical data of 1 were consistent with the reported ones.10c,17
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Preparation of
N1-substituted benzo[1,2,3]triazin-4-one derivatives 3aa via
L1AuNTf2-catalyzed reaction of 3-hydroxybenzo[1,2,3]triazin-4(3H)-ones 1 and alkynes 2.
Typical procedure (3aa as example): 3-hydroxybenzo[1,2,3]triazin-4(3H)-one 1a (32.6 mg, 0.2 mmol),
L1AuNTf2 (2.1 mg, 1 mol %) were placed in a 10 mL Schrenk tube. The tube was evacuated and
refilled with N2 three times. Phenylacetylene 2a (24.5 mg, 1.2 equiv based on 1a) and DCM (1.0 mL)
was added and the resulting mixture was stirred and heated in an oil bath at 80 °C for 4 h. Upon
completion, the reaction mixture was was evaporated and purified by column chromatography on silica
gel (100-200 mesh), eluting with the indicated mixture of EA/PE (1:1 (V/V)) to give pure product 3aa.
Characterization of the products.
1-(2-oxo-2-phenylethyl)benzo[1,2,3]triazin-4(1H)-one (3aa): Product was isolated via column
1
chromatography (eluent PE/EA = 1:1 (V/V)) as a yellow solid (51.9 mg, 98%). m.p.: 165-167 °C. H
NMR (500 MHz, CDCl3): δ 8.36 (dd, J1 = 7.8 Hz, J2 = 0.8 Hz, 1H), 8.00-7.96 (m, 2H), 7.91-7.83 (m,
13
3H), 7.70-7.65 (m, 1H), 7.57-7.52 (m, 2H), 6.12 (s, 2H). C{1H} NMR (126 MHz, CDCl3): δ 188.3,
167.7, 146.4, 134.7, 134.5, 133.83, 133.80, 129.2, 128.1, 126.5, 125.6, 117.7, 74.1. HRMS (ESI) m/z:
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[M+H]+ Calcd for C15H12N3O2 266.0924; Found 266.0928.
4
5
6
7
1-(2-oxo-2-(o-tolyl)ethyl)benzo[1,2,3]triazin-4(1H)-one (3ab): Product was isolated via column
8
9
1
chromatography (eluent PE/EA = 1:1 (V/V)) as a white solid (50.8 mg, 91%). m.p.: 204-206 °C. H
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11
12
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NMR (500 MHz, CDCl3): δ 8.34 (d, J = 7.8 Hz, 1H), 7.90-7.85 (m, 2H), 7.85-7.80 (m, 1H), 7.75 (d, J =
13
7.5 Hz, 1H), 7.50-7.45 (m, 1H), 7.36-7.29 (m, 2H), 6.03 (s, 2H), 2.54 (s, 3H). C{1H} NMR (126
MHz, CDCl3): δ 190.5, 167.8, 146.39, 140.36, 134.5, 133.7, 133.2, 133.2, 132.7, 128.6, 126.4, 126.2,
125.5, 117.7, 75.3, 21.6. HRMS (ESI) m/z: [M+H]+ Calcd for C16H14N3O2 280.1081; Found 280.1084.
1-(2-(2-(dimethylamino)phenyl)-2-oxoethyl)benzo[1,2,3]triazin-4(1H)-one (3ac): Product was
1
isolated via column chromatography (eluent PE/EA = 1:1 (V/V)) as a brown oil (59.2 mg, 96%). H
NMR (500 MHz, CDCl3): δ 8.34-8.32 (m, 1H), 7.87-7.86 (m, 2H), 7.83-7.80 (m, 1H), 7.56 (dd, J1 =
7.8 Hz, J2 = 1.8 Hz, 1H), 7.48-7.45 (m, 1H), 7.14-7.11 (m, 1H), 7.06-7.02 (m, 1H), 6.14 (s, 2H), 2.87
13
(s, 6H). C{1H} NMR (126 MHz, CDCl3): δ 192.8, 167.8, 153.3, 146.4, 134.3, 133.6, 133.5, 130.4,
129.44, 126.35, 125.5, 122.0, 118.4, 117.6, 75.8, 45.2. HRMS (ESI) m/z: [M+H]+ Calcd for
C17H17N4O2 309.1346; Found 309.1343.
1-(2-(2-chlorophenyl)-2-oxoethyl)benzo[1,2,3]triazin-4(1H)-one (3ad): Product was isolated via
column chromatography (eluent PE/EA = 1:1 (V/V)) as a yellow solid (49.2 mg, 82%). m.p.:
161-164 °C. 1H NMR (500 MHz, CDCl3): δ 8.36 (d, J = 7.8 Hz, 1H), 7.91-7.88 (m, 2H), 7.88-7.83 (m,
1H), 7.78 (dd, J1 = 8.0 Hz, J2 = 1.0 Hz, 1H), 7.54-7.48 (m, 2H), 7.44-7.39 (m, 1H), 6.11 (s, 2H).
13C{1H} NMR (126 MHz, CDCl3): δ 190.0, 167.7, 146.4, 134.7, 134.6, 134.0, 133.9, 132.2, 131.1,
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130.7, 127.5, 126.5, 125.6, 117.7, 76.6. HRMS (ESI) m/z: [M+H]+ Calcd for C15H11ClN3O2 300.0534;
Found 300.0538.
8
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1-(2-oxo-2-(m-tolyl)ethyl)benzo[1,2,3]triazin-4(1H)-one (3ae): Product was isolated via column
10
11
12
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1
chromatography (eluent PE/EA = 1:1 (V/V)) as a yellow solid (53.1 mg, 95%). m.p.: 153-156 °C. H
NMR (500 MHz, CDCl3): δ 8.34 (d, J = 8.0 Hz, 1H), 7.90-7.80 (m, 3H), 7.76-7.73 (m, 2H), 7.48-7.45
(m, 1H), 7.42-7.38 (m,1H), 6.10 (s, 2H), 2.42 (s, 3H). C{1H} NMR (126 MHz, CDCl3): δ 188.5,
13
167.7, 146.4, 139.1, 135.5, 134.4, 133.8, 133.7, 129.0, 128.5, 126.4, 125.5, 125.3, 117.7, 74.1, 21.3.
HRMS (ESI) m/z: [M+H]+ Calcd for C16H14N3O2 280.1081; Found 280.1077.
1-(2-(3-methoxyphenyl)-2-oxoethyl)benzo[1,2,3]triazin-4(1H)-one (3af): Product was isolated via
column chromatography (eluent PE/EA = 1:1 (V/V)) as a yellow solid (56.7 mg, 96%). mp:
190-193 °C. 1H NMR (500 MHz, CDCl3): δ 8.37-8.30 (m, 1H), 7.96-7.91 (m, 2H), 7.89-7.81 (m, 3H),
7.01-6.96 (m, 2H), 6.06 (s, 2H), 3.88 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 186.7, 167.7, 164.7,
146.4, 134.4, 133.7, 130.5, 126.8, 126.4, 125.5, 117.7, 114.4, 73.8, 55.6. HRMS (ESI) m/z: [M+H]+
Calcd for C16H14N3O3 296.1030; Found 296.1035.
1-(2-(3-bromophenyl)-2-oxoethyl)benzo[1,2,3]triazin-4(1H)-one (3ag): Product was isolated via
column chromatography (eluent PE/EA = 1:1 (V/V)) as a yellow solid (52.3 mg, 76%). m.p.:
182-185 °C. 1H NMR (500 MHz, CDCl3): δ 8.36 (d, J = 8.0 Hz, 1H), 8.11-8.09 (m,1H), 7.92-7.84 (m,
4H), 7.80 (dd, J1 = 8.0 Hz, J2 = 1.0 Hz, 1H), 7.46–7.42 (m,1H), 6.09 (s, 2H). 13C{1H} NMR (126 MHz,
CDCl3): δ 187.25, 167.69, 146.43, 137.63, 135.53, 134.60, 133.98, 131.11, 130.78, 126.63, 126.50,
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125.67, 123.57, 117.78, 73.92. HRMS (ESI) m/z: [M+H]+ Calcd for C15H11BrN3O2 344.0029; Found
344.0025.
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1-(2-oxo-2-(p-tolyl)ethyl)benzo[1,2,3]triazin-4(1H)-one (3ah): Product was isolated via column
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chromatography (eluent PE/EA = 1:1 (V/V)) as a yellow solid (51.9 mg, 93%). m.p.: 159-161 °C. H
NMR (500 MHz, CDCl3): δ 8.32 (d, J = 8.0 Hz, 1H), 7.89-7.78 (m, 5H), 7.30 (d, J = 8.0 Hz, 2H), 6.08
(s, 2H), 2.41 (s, 3H). C{1H} NMR (126 MHz, CDCl3): δ 187.9, 167.7, 146.4, 145.9, 134.4, 133.7,
13
131.3, 129.8, 128.2, 126.4, 125.5, 117.6, 74.0, 21.8. HRMS (ESI) m/z: [M+H]+ Calcd for C16H14N3O2
280.1081; Found 280.1076.
1-(2-(4-methoxyphenyl)-2-oxoethyl)benzo[1,2,3]triazin-4(1H)-one (3ai): Product was isolated via
column chromatography (eluent PE/EA = 1:1 (V/V)) as a yellow solid (56.7 mg, 96%). m.p.:
161-164 °C. 1H NMR (500 MHz, CDCl3): δ 8.32 (d, J = 7.5 Hz, 1H), 7.94-7.91(m, 2H), 7.87-7.79 (m,
3H), 6.98-6.95 (m, 2H), 6.06 (s, 2H), 3.87 (s, 3H). C{1H} NMR (126 MHz, CDCl3): δ 186.7, 167.7,
13
164.7, 146.4, 134.4, 133.7, 130.5, 126.7, 126.4, 125.5, 117.6, 114.4, 73.8, 55.6. HRMS (ESI) m/z:
[M+H]+ Calcd for C16H14N3O3 296.1030; Found 296.1035.
1-(2-([1,1'-biphenyl]-4-yl)-2-oxoethyl)benzo[1,2,3]triazin-4(1H)-one (3aj): Product was isolated
via column chromatography (eluent PE/EA = 1:1 (V/V)) as a yellow solid (64.8 mg, 95%). m.p.:
219-220 °C. 1H NMR (500 MHz, CDCl3): δ 8.37 (d, J = 8.0 Hz, 1H), 8.06-8.02 (m, 2H), 7.90-7.82 (m,
3H), 7.76-7.73 (m, 2H), 7.65-7.62 (m, 2H), 7.52-7.47 (m, 2H), 7.45-7.41(m, 1H), 6.15 (s, 2H). 13C{1H}
NMR (126 MHz, CDCl3): δ 187.9, 167.8, 147.4, 146.4, 139.2, 134.5, 133.8, 132.5, 129.04, 128.7,
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128.6, 127.7, 127.3, 126.5, 125.6, 117.7, 74.1. HRMS (ESI) m/z: [M+H]+ Calcd for C21H16N3O2
342.1237; Found 342.1232.
8
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methyl 4-(2-(4-oxobenzo[1,2,3]triazin-1(4H)-yl)acetyl)benzoate (3ak): Product was isolated via
column chromatography (eluent PE/EA = 1:1 (V/V) as a light red solid (50.4 mg, 78%). m.p.:
201-204 °C. 1H NMR (500 MHz, CDCl3): δ 8.33 (d, J = 7.5 Hz, 1H), 8.17-8.15 (m, 2H), 8.04-8.01 (m,
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11
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2H), 7.90-7.81 (m, 3H), 6.16 (s, 2H), 3.95 (s, 3H). C{1H} NMR (126 MHz, CDCl3): δ 188.1, 167.7,
165.7, 146.4, 136.9, 135.3, 134.6, 134.0, 130.3, 128.1, 126.5, 125.6, 117.7, 74.2, 52.6. HRMS (ESI)
m/z: [M+H]+ Calcd for C17H14N3O4 324.0979; Found 324.0977.
1-(2-(2,4-dimethylphenyl)-2-oxoethyl)benzo[1,2,3]triazin-4(1H)-one (3al): Product was isolated
via column chromatography (eluent PE/EA = 1:1 (V/V) as a yellow solid (52.7 mg, 90%). m.p.:
165-168 °C. 1H NMR (500 MHz, CDCl3): δ 8.34-8.32 (m, 1H), 7.89-7.83 (m, 2H), 7.83-7.78 (m, 1H),
13
7.66 (d, J = 7.5 Hz, 1H), 7.15-7.09 (m, 2H), 6.02 (s, 2H), 2.51 (s, 3H), 2.36 (s, 3H). C{1H} NMR
(126 MHz, CDCl3): δ 189.6, 167.7, 146.3, 144.3, 140.8, 134.4, 133.6, 133.6, 130.2, 129.1, 126.8,
126.4, 125.5, 117.6, 75.2, 21.8, 21.5. HRMS (ESI) m/z: [M+H]+ Calcd for C17H16N3O2 294.1237;
Found 294.1243.
1-(2-(3,5-dimethylphenyl)-2-oxoethyl)benzo[1,2,3]triazin-4(1H)-one (3am): Product was isolated
via column chromatography (eluent PE/EA = 1:1 (V/V) as a white solid (52.7 mg, 90%). m.p.:
1
190-193 °C. H NMR (500 MHz, CDCl3): δ 8.37-8.31 (m, 1H), 7.90-7.81 (m, 3H), 7.55 (s, 2H), 7.29
(s, 1H), 6.07 (s, 2H), 2.38 (s, 6H). 13C{1H} NMR (126 MHz, CDCl3): δ 188.6, 167.7, 146.4, 138.9,
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136.4, 134.4, 133.9, 133.7, 126.4, 125.8, 125.5, 117.7, 74.1, 21.1. HRMS (ESI) m/z: [M+H]+ Calcd for
C17H16N3O2 294.1237; Found 294.1241.
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1-(2-(naphthalen-2-yl)-2-oxoethyl)benzo[1,2,3]triazin-4(1H)-one (3an): Product was isolated via
column chromatography (eluent PE/EA = 1:1 (V/V) as a yellow solid (59.2 mg, 94%). m.p.:
154-157 °C. 1H NMR (500 MHz, CDCl3): δ 8.50 (s, 1H), 8.37 (d, J = 8.0 Hz, 1H), 8.02-7.97 (m, 2H),
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7.96-7.93 (m, 1H), 7.91-7.81 (m, 4H), 7.68-7.65 (m, 1H), 7.62-7.59 (m, 1H), 6.25 (s, 2H). C{1H}
NMR (126 MHz, CDCl3): δ 188.3, 167.8, 146.5, 136.2, 134.5, 133.8, 132.3, 131.2, 130.3, 129.8, 129.4,
129.3, 127.9, 127.4, 126.5, 125.6, 123.1 , 117.8, 74.1. HRMS (ESI) m/z: [M+H]+ Calcd for
C19H14N3O2 316.1081; Found 316.1078.
1-(2-oxo-2-(pyridin-2-yl)ethyl)benzo[1,2,3]triazin-4(1H)-one (3ao): Product was isolated via
column chromatography (eluent PE/EA = 1:1 (V/V) as a brown solid (43.6 mg, 82%). m.p.:
123-126 °C. 1H NMR (500 MHz, CDCl3): δ 8.60 (dd, J = 4.8, 0.8 Hz, 1H), 8.32 (dd, J1 = 7.8 Hz, J2 =
1.3 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.90-7.85 (m, 1H), 7.84-7.79 (m, 1H), 7.77-7.72 (m, 1H), 7.57
(d, J = 7.8 Hz, 1H), 7.32-7.28 (m, 1H), 5.90 (s, 2H). 13C{1H} NMR (126 MHz, CDCl3): δ 167.9, 152.3,
149.9, 146.5, 137.3, 134.4, 133.6, 126.7, 125.5, 124.0, 123.8, 117.8, 74.5. HRMS (ESI) m/z: [M+H]+
Calcd for C14H11N4O2 267.0877; Found 267.0880.
1-(2-oxo-2-(thiophen-2-yl)ethyl)benzo[1,2,3]triazin-4(1H)-one (3ap): Product was isolated via
column chromatography (eluent PE/EA = 1:1 (V/V) as a gray solid (47.7 mg, 88%). m.p.: 200-203 °C.
1H NMR (500 MHz, DMSO-d6): δ 8.24-8.19 (m, 3H), 8.08-8.02 (m, 2H), 7.80-7.96 (m, 1H), 7.39 (dd,
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J1 = 5.0 Hz, J2 = 4.0 Hz, 1H), 6.46 (s, 2H). C{1H} NMR (126 MHz, DMSO-d6): δ 183.5, 166.6,
145.9, 139.9, 137.3, 135.6, 135.2, 134.3, 129.3, 126.5, 124.8 , 117.1, 74.0. HRMS (ESI) m/z: [M+H]+
Calcd for C13H10N3O2S 272.0488; Found 272.0483.
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1-(2-oxooctyl)benzo[1,2,3]triazin-4(1H)-one (3aq): Product was isolated via column
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chromatography (eluent PE/EA = 1:1 (V/V) as a white solid (53.0 mg, 97%). m.p.: 105-108 °C. H
NMR (500 MHz, CDCl3): δ 8.33 (d, J = 8.0 Hz, 1H), 7.92-7.79 (m, 3H), 5.47 (s, 2H), 2.59 (t, J = 7.5
13
Hz, 2H), 1.68-1.59 (m, 2H), 1.34-1.23 (m, 6H), 0.86 (t, J = 6.8 Hz, 3H). C{1H} NMR (126 MHz,
CDCl3): δ 198.8, 167.7, 146.3, 134.5, 133.8, 126.4, 125.6, 117.6, 76.0, 40.4, 31.4, 28.6, 23.2, 22.3,
13.9. HRMS (ESI) m/z: [M+H]+ Calcd for C15H20N3O2 274.1550; Found 274.1554.
1-(2-oxo-4-phenylbutyl)benzo[1,2,3]triazin-4(1H)-one (3ar): Product was isolated via column
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chromatography (eluent PE/EA = 1:1 (V/V) as a white solid (55.7 mg, 95%). m.p.: 182-185 °C. H
NMR (500 MHz, CDCl3): δ 8.38-8.31 (m, 1H), 7.91-7.82 (m, 3H), 7.30-7.26 (m, 2H), 7.23-7.16 (m,
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3H), 5.45 (s, 2H), 3.00-2.96 (m, 2H), 2.95-2.91 (m, 2H). C{1H} NMR(126 MHz, CDCl3): δ 198.0,
167.6, 146.3, 139.7, 134.6, 133.9, 128.7, 128.3, 126.5, 126.5, 125.6, 117.7, 76.1, 41.9, 29.1. HRMS
(ESI) m/z: [M+H]+ Calcd for C17H16N3O2 294.1237; Found 294.1235.
1-(5-chloro-2-oxopentyl)benzo[1,2,3]triazin-4(1H)-one (3as): Product was isolated via column
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chromatography (eluent PE/EA = 1:1 (V/V) as a yellow solid (17.5 mg, 33%). m.p.: 129-132 °C. H
NMR (500 MHz, CDCl3): δ 8.36-8.32 (m, 1H), 7.92-7.84 (m, 3H), 5.53 (s, 2H), 3.60 (t, J = 6.3 Hz,
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2H), 2.83 (t, J = 6.8 Hz, 2H), 2.17-2.10 (m, 2H). C{1H} NMR( 126 MHz, CDCl3): δ 198.0, 167.6,
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146.3, 134.6, 134.0, 126.5, 125.6, 117.7, 76.0, 43.8, 37.0, 25.7. HRMS (ESI) m/z: [M+H]+ Calcd for
C12H13ClN3O2 266.0691; Found 266.0687.
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1-(2-cyclopropyl-2-oxoethyl)benzo[1,2,3]triazin-4(1H)-one (3at): Product was isolated via column
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chromatography (eluent PE/EA = 1:1 (V/V) as a white solid (44.9 mg, 98%). m.p.: 133-136 °C. H
NMR (500 MHz, CDCl3): δ 8.30 (d, J = 8.0 Hz, 1H), 7.89-7.78 (m, 3H), 5.64 (s, 2H), 2.04-1.98 (m,
1H), 1.25-1.19 (m, 2H), 1.09-1.04 (m, 2H). C{1H} NMR (126 MHz, CDCl3): δ 198.8, 167.6, 146.3,
13
134.5, 133.8, 126.4, 125.4, 117.6, 76.5, 18.9, 12.4. HRMS (ESI) m/z: [M+H]+ Calcd for C12H12N3O2
230.0924; Found 230.0927.
1-(3,3-dimethyl-2-oxobutyl)benzo[1,2,3]triazin-4(1H)-one (3au): Product was isolated via column
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chromatography (eluent PE/EA = 1:1 (V/V) as a white solid (40.7 mg, 83%), m.p.: 204- 207 °C. H
NMR (500 MHz, CDCl3): δ 8.33 (d, J = 8.0 Hz, 1H), 7.89-7.79 (m, 3H), 5.65 (s, 2H), 1.29 (s, 9H).
13C{1H} NMR (126 MHz, CDCl3): δ 203.6, 167.8, 146.4, 134.4, 133.7, 126.3, 125.5, 117.6, 72.5, 43.9,
26.0. HRMS (ESI) m/z: [M+H]+ Calcd for C13H16N3O2 246.1237; Found 246.1233.
6-methyl-1-(2-oxo-2-phenylethyl)benzo[1,2,3]triazin-4(1H)-one (3ba): Product was isolated via
column chromatography (eluent PE/EA = 1:1 (V/V) as a white solid (54.1 mg, 97%), m.p.: 200-203 °C.
1H NMR (500 MHz, CDCl3): δ 8.16 (s, 1H), 7.98-7.96 (m, 2H), 7.79 (d, J = 8.5 Hz, 1H), 7.72-7.66 (m,
2H), 7.56-7.52 (m, 2H), 6.08 (s, 2H), 2.59 (s, 3H). C{1H} NMR (126 MHz, CDCl3): δ 188.4, 167.7,
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145.6, 144.7, 136.1, 134.7, 133.9, 129.2, 128.1, 126.4, 124.8, 117.7, 73.8, 22.2. HRMS (ESI) m/z:
[M+H]+ Calcd for C16H14N3O2 280.1081; Found 280.1086.
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6-chloro-1-(2-oxo-2-phenylethyl)benzo[1,2,3]triazin-4(1H)-one (3ca): Product was isolated via
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column chromatography (eluent PE/EA = 1:1 (V/V) as a yellow solid (55.1 mg, 92%). m.p.:
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187-190 °C. H NMR (500 MHz, DMSO-d6): δ 8.15 (s, 1H), 8.09 - 8.06 (m, 4H), 7.77 (t, J = 7.5 Hz,
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1H), 7.63 (t, J = 7.8 Hz, 2H), 6.58 (s, 2H). C{1H} NMR (126 MHz, DMSO-d6): δ 191.1, 166.0,
145.1, 138.9, 136.1, 135.2, 134.2, 129.6, 129.3, 128.9, 124.4, 118.7, 75.2. HRMS (ESI) m/z: [M+H]+
Calcd for C15H11ClN3O2 300.0534; Found 300.0529.
7-methyl-1-(2-oxo-2-phenylethyl)benzo[1,2,3]triazin-4(1H)-one (3da): Product was isolated via
column chromatography chromatography (eluent PE/EA = 1:1 (V/V) as a white solid (51.9 mg, 93%).
1
m..p: 225-228 °C. H NMR (500 MHz, CDCl3): δ 8.26 (d, J = 8.0 Hz, 1H), 7.99-7.95 (m, 2H),
7.70-7.65 (m, 3H), 7.57-7.52 (m, 2H), 6.09 (s, 2H), 2.56 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ
188.3, 167.7, 146.7, 145.7, 135.6, 134.7, 133.9, 129.2, 128.1, 125.6, 125.4, 115.6, 74.0, 21.9. HRMS
(ESI) m/z: [M+H]+ Calcd for C16H14N3O2 280.1081; Found 280.1083.
8-methyl-1-(2-oxo-2-phenylethyl)benzo[1,2,3]triazin-4(1H)-one (3ea): Product was isolated via
column chromatography (eluent PE/EA = 1:1 (V/V) as a yellow solid (54.7 mg, 98%). m.p.:
1
201-204 °C. H NMR (500 MHz, CDCl3) δ 8.19-8.15 (m, 1H), 7.99-7.95 (m, 2H), 7.71-7.63 (m, 3H),
7.54-7.50 (m, 2H), 6.13 (s, 2H), 2.58 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 188.5, 168.1, 145.2,
136.3, 135.0, 134.6, 133.8, 133.5, 129.1, 128.1, 123.0, 117.9, 74.1, 16.8. HRMS (ESI) m/z: [M+H]+
Calcd for C16H14N3O2 280.1081; Found 280.1079.
7,8-dimethyl-1-(2-oxo-2-phenylethyl)benzo[1,2,3]triazin-4(1H)-one (3fa): Product was isolated
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via column chromatography (eluent PE/EA = 1:1 (V/V) as a yellow solid (56.9 mg, 97%). m.p.:
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217-220 °C. 1H NMR (500 MHz, CDCl3): δ 8.11 (d, J = 8.0 Hz, 1H), 7.99-7.95 (m, 2H), 7.68-7.61 (m,
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2H), 7.55-7.51 (m, 2H), 6.12 (s, 2H), 2.50 (s, 3H), 2.45 (s, 3H). C{1H} NMR (126 MHz, CDCl3): δ
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188.5, 168.3, 145.1, 143.6, 136.0, 134.6, 134.0, 133.9, 129.1, 128.1, 122.3, 116.1, 74.1, 20.5, 12.8.
HRMS (ESI) m/z: [M+H]+ Calcd for C17H16N3O2 294.1237; Found 294.1233.
1 mmol-scale synthesis of 3aa. 3-hydroxybenzo[1,2,3]triazin-4(3H)-one 1a (163.0 mg, 1.0 mmol),
L1AuNTf2 (10.5 mg, 1 mol %) were placed in a 15 mL Schrenk tube. The tube was evacuated and
refilled with N2 three times. Phenylacetylene 2a (122.5 mg, 1.2 mmol, 1.2 equiv based on 1a) and
DCM (5.0 mL) was added and the resulting mixture was stirred and heated in an oil bath at 80 °C for
28 h. Upon completion, the reaction mixture was was evaporated and purified by column
chromatography on silica gel (100-200 mesh), eluting with the indicated mixture of EA/PE (1:1 (V/V))
to give pure product 3aa (0.26 g, 97%).
Mechanistic studies.
Synthesis and isolation of intermediate 4.
3-hydroxybenzo[1,2,3]triazin-4(3H)-one 1a (65.2 mg, 0.4 mmol), L1AuNTf2 (4.2 mg, 1 mol %) were
placed in a 10 mL Schrenk tube. The tube was evacuated and refilled with N2 three times.
Phenylacetylene 2a (49.0 mg, 1.2 equiv based on 1a) and DCM (1.5 mL) was added and the resulting
mixture was stirred at 10 °C for 24 h. Upon completion, the reaction mixture was was evaporated and
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purified by column chromatography on silica gel (100-200 mesh), eluting with the indicated mixture of
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EA/PE (10:1 (V/V) to give pure product 4 (37.1 mg, 35%).
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3-((1-phenylvinyl)oxy)benzo[1,2,3]triazin-4(3H)-one (4):
4
was isolated via column
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chromatography (PE/EA = 10:1 (V/V)) as a white solid. m.p.: 97-98 °C. 1H NMR (500 MHz, CDCl3):
δ 8.45 (dd, J1 = 8.0 Hz, J2 = 1.0 Hz, 1H), 8.30-8.26 (m, 1H), 8.07-8.02 (m, 1H), 7.90-7.83 (m, 3H),
13
7.48-7.42 (m, 3H), 4.96 (d, J = 4.0 Hz, 1H), 4.32 (d, J = 4.0 Hz, 1H). C{1H} NMR (126 MHz,
CDCl3): δ 160.8, 150.3, 144.3, 135.3, 132.6, 132.2, 129.8, 129.0, 128.5, 126.4, 125.8, 122.5, 88.0.
HRMS (ESI) m/z: [M+H]+ calcd for C15H12N3O2 266.0924; found 266.0927.
Subjection of intermediate 4 to the standard reaction conditions (or in the absence of gold(I)
catalyst) and its conversion to 3aa.
4 (39.8 mg, 0.15 mmol), L1AuNTf2 (1.6 mg, 1 mol %), and DCM (0.75 mL) were placed in a 10 mL
Schrenk tube. The tube was evacuated and refilled with N2 three times. The resulting mixture was
stirred and heated in an oil bath at 80 °C for 4 h. Upon completion, the reaction mixture was was
evaporated and purified by column chromatography on silica gel (100-200 mesh), eluting with the
indicated mixture of EA/PE (1:1 (V/V)) to give pure product 3aa (39.3 mg, 99%). When 4 was
subjected to the above mentioned conditions except in the absence of a gold(I) catalyst, 3aa was still
obtained in 84% yield (33.3 mg).
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ASSOCIATED CONTENT
Supporting Information
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Copies of H and C{1H} NMR spectra of the products and reaction intermediate 4. This material is
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available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: ykuiliu@zjut.edu.cn; jhwei828@zjut.edu.cn
Author Contributions
§These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful to the Natural Science Foundation of China (No. 21772176 and 21372201) and
Zhejiang Province (Grant No. LY20B020013) for financial support.
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