Cobalt-catalyzed carbonylative synthesis of phthalimides from n-(pyridin-2-ylmethyl)benzamides with tfben as the co source

Article abstract of DOI:10.1021/acs.joc.9b01890

A cobalt-catalyzed direct carbonylative synthesis of phthalimide motifs from N-(pyridin-2-ylmethyl)benzamides has been developed. Various phthalimide derivatives were obtained in moderate to excellent yields (up to 98percent) by using 2-picolylamine as an efficient directing group and benzene-1,3,5-triyl triformate (TFBen) as a convenient CO surrogate.

Full text of DOI:10.1021/acs.joc.9b01890

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Cobalt-Catalyzed Carbonylative Synthesis of Phthalimides from
N-(pyridin-2-ylmethyl)benzamides with TFBen as the CO Source
Luyang Fu, Jun Ying, and Xiao-Feng Wu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01890 • Publication Date (Web): 09 Sep 2019
Downloaded from pubs.acs.org on September 9, 2019
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The Journal of Organic Chemistry
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Cobalt-Catalyzed Carbonylative Synthesis of Phthalimides from N-
(pyridin-2-ylmethyl)benzamides with TFBen as the CO Source
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Lu-Yang Fu,a Jun Ying,*a and Xiao-Feng Wu*a,b
a Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People’s Republic of
China
b Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Straβe 29a, 18059 Rostock, Germany.
Supporting Information Placeholder
O
O
Co(acac)2, Ag2CO3, AcOH
1,4-dioxane, 130 °C, 10 h
N
+
TFBen
N
H
N
R
R
N
O
OCHO
23 examples
up to 98% yield
OHCO
OCHO
TFBen
ABSTRACT:
A
cobalt-catalyzed direct carbonylative synthesis of phthalimide motifs from N-(pyridin-2-
ylmethyl)benzamides has been developed. With 2-picolylamine as an efficient directing group and benzene-1,3,5-triyl
triformate (TFBen) as a convenient CO surrogate, various phthalimide derivatives were obtained in moderate to excellent
yields (up to 98%).
Transition-metal-catalyzed carbonylation reaction is one
of the most straightforward and efficient tools for the
synthesis of carbonyl-containing compounds.1,2 Among the
develop procedures, the direct C-H carbonylation of
benzamides for constructing phthalimide motifs has been
developed recently.3-7 In these methods, directing groups
such as 8-aminoqinoline are generally used together with
Co,3 Cu,4 or Ni5 catalysts (Scheme 1, eq a). For instance,
Zhang and co-workers established a convenient approach
for C-H carbonylation of benzamides using Co(OAc)2·4H2O
as the catalyst and azodicarboxylates as the CO source.3b
gas with 10 bar of carbon monoxide and 7 bar of ethylene
is needed.
Scheme 1. Synthesis of Phthalimides via Direct
Carbonylation of Benzamides.
Previous works
O
O
[Co] or [Cu] or [Ni]
[CO]
N
a)
N
H
N
N
O
Lei and co-workers developed
a
Co-catalyzed
O
O
electrochemical oxidative C-H/N-H carbonylation for the
synthesis of phthalimides.3d Li, Ge and their co-workers
realized a Cu-catalyzed C-H carbonylation of benzamides
employing nitromethane as the CO source.4a Additionally,
Ge’s group also reported procedure on direct
carbonylation the C-H bonds of aromatic amides through
Ni/Cu synergistic catalysis with DMF as the CO surrogate.5
Interestingly, 2-picolylamine could be an effective
directing group in direct C-H carbonylation of benzamides
as well, while limited examples were reported.6 Chatani’s
research group demonstrated that aromatic amides having
2-picolylamine as the directing group could successfully
undergo Ru-catalyzed ortho carbonylation to give
phthalimides (Scheme 1, eq b).6a In this procedure, a mixed
Ru3(CO)12 (5 mol %)
N
b)
N
H
CO (10 atm), ethylene (7 atm)
N
N
O
This work
c)
O
O
Co(acac)2
N
N
TFBen
H
N
N
O
OCHO
OHCO
OCHO
TFBen
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16c,e
17c,f
18c,g
Co(acac)2
Co(acac)2
Co(acac)2
AcOH
AcOH
AcOH
dioxane
dioxane
dioxane
89
55
64
On the other hand, in order to avoid the direct
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5
6
7
8
manipulation of CO gas in carbonylative reactions, various
CO surrogates have been developed.8 Among them, TFBen,
developed by our group,9,10 is a solid, safe, and convenient
CO source. Herein, we wish to report our results on Co-
catalyzed direct carbonylative transformation of N-
(pyridin-2-ylmethyl)benzamides into phthalimides with
TFBen as the CO source.
aReaction condition: 1a (0.3 mmol), TFBen (2.0 equiv),
[Co] (20 mol %), Ag2CO3 (2.0 equiv), 1,4-dioxane (2 mL),
130 º C, 10 h. bYields were determined by GC with
dodecane as an internal standard. TFBen (3.0 equiv).
dIsolated yield. eCo(acac)2 (10 mol %). f110 ºC. g150 ºC.
c
At the outset, N-(pyridin-2-ylmethyl)benzamide 1a was
selected as the model substrate with TFBen (2.0 equiv) as
the CO source in the presence of the cobalt catalyst (20 mol
%) and using Ag2CO3 (2.0 equiv) as an oxidant at 130 oC for
10 h (Table 1, entries 1-4). It was found the reaction with
Co(acac)2 gave the desired product 2a in 11% yield (Table
1, entry 1). Next, a series of basic or acidic additives were
examined (Table 1, entries 5-10). Fortunately, using AcOH
as the additive remarkably enhanced the yield to 63%
(Table 1, entry 10). It is much likely that the addition of
AcOH tunes the acidity of the catalytic system and
promotes the C-H activation step. Moreover, other solvents
such as THF, dioxane, DMF, and MeCN were tested as well
(Table 1, entries 11-14). We were delighted to find that the
reaction using dioxane as a solvent significantly improved
the yield to 82% (Table 1, entry 12). When the amount of
TFBen was increased (3.0 equiv), product 2a was obtained
in 88% isolated yield (Table 1, entry 15). In addition, it was
shown that reducing the amount of Co(acac)2 slightly
decreased the yield of 2a (Table 1, entry 16). Finally,
raising or reducing the temperature hampered the
reaction dramatically (Table 1, entry 17 and 18). Other
oxidants such as BQ, K2S2O8 and TEMPO were also tested
but failed to give product 2a.
9
With the optimal reaction conditions in hand, we
subsequently explored the substrate scope of N-(pyridin-2-
ylmethyl)benzamides as illustrated in Scheme 2.
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Scheme 2. Phthalimide Synthesis: Scope of N-(pyridin-
2-ylmethyl)benzamides.a
Table 1. Phthalimide Synthesis: Screening of Reaction
Conditions.a
O
O
[Co], TFBen
N
N
H
oxidant, additive
solvent, T
N
N
O
1a
2a
entry
[Co]
additive solvent
yield
(%)b
1
2
Co(acac)2
Co(acac)3
Co(OAc)2•4H2O
CoCl2
\
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
11
10
5
\
3
\
4
\
3
5
Co(acac)2
Co(acac)2
Co(acac)2
Co(acac)2
Co(acac)2
Co(acac)2
Co(acac)2
Co(acac)2
Co(acac)2
Co(acac)2
Co(acac)2
Na2CO3
NaOPiv
Et3N
TFA
n.d.
33
21
13
40
63
67
82
17
40
6
7
8
9
PivOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
10
11
12
13
14
15c
dioxane
DMF
MeCN
dioxane 91 (88d)
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Co(acac)2 (20 mol %)
Ag2CO3 (2.0 equiv)
AcOH (2.0 equiv)
O
yields. Moreover, the reaction of the 4-phenyl substituted
N-(pyridin-2-ylmethyl)benzamide 1o affords the
O
1
1
2
3
4
5
6
7
8
N
N
+
TFBen
H
corresponding product 2o in 83% yield. It was found that
the 1-naphthyl amide 1p could be transformed to the
expected product 2p in good yield as well. Interestingly,
when the 2-naphthyl amide 1q was subjected to the
standard reaction conditions, two regiomers (2q and 2p)
with a ratio of 1.88:1 were achieved in an excellent yield
(98%). It was noted that compounds with ortho-
substituent that are either electron-donating (methyl) or
electron-withdrawing (fluoro, chloro) all gave the
corresponding products 2r-t in high yields. Additionally,
di-substituted N-(pyridin-2-ylmethyl)benzamides were
tolerated as well to access the products 2u-v in moderate
to high yields. Gratifyingly, substrate 1w containing a
thiophene unit could be successfully converted into the
desired product 2w, albeit in a low yield (33%).
To illustrate the synthetic utility of this method, the
gram-scale experiment was performed and further
transformations of phthalimides were demonstrated as
well (Scheme 3). Treatment of the N-(pyridin-2-
ylmethyl)benzamide 1a (1.06 g, 5 mmol) with TFBen (2.0
equiv) under standard reaction conditions afforded the
phthalimide 2a in 81% yield (0.96 g; Scheme 3, eq a).
Subsequently, selective reduction of 2a with zinc (7.6
equiv) led to the formation of the amide 3a in 78% yield
(Scheme 3, eq b). Furthermore, when 2a was reacted with
aqueous KOH solution (4.5 M, 3 mL), phthalic acid 4a was
achieved in 91% yield (Scheme 3, eq c).
N
1,4-dioxane (2 mL)
130 °C, 10 h
R
(3.0 equiv)
N
O
R
2
O
O
O
N
N
N
N
N
N
O
O
O
2c, 85%
O
2b, 95%
2a, 88%
9
O
O
10
11
12
13
14
15
16
17
18
19
20
21
22
N
N
N
O
N
N
N
N
O
O
O
2f, 35%
O
2d, 91%
2e, 90%
O
O
N
N
N
F
Cl
Br
N
N
N
O
O
O
2g, 90%
O
2h, 90%
2i, 76%
O
O
N
N
N
F3C
F3CO
NC
N
N
N
O
O
O
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2l, 68%b
O
2j, 76%
2k, 89%
O
O
N
N
O2N
N
N
Ph
O
MeOOC
Scheme 3. Gram-Scale Reactions and Transformations
of Product 2a.
N
O
N
O
2n, 31%
2o, 83%b
2m, 52%
Co(acac)2 (20 mol %)
Ag2CO3 (2.0 equiv)
AcOH (2.0 equiv)
O
a)
O
O
N
N
N
H
O
N
O
+ TFBen
O
N
1,4-dioxane
130 °C, 10 h
N
O
1a
2a
0.96 g, 81%
N
5 mmol, 1.06 g
(2.0 equiv)
N
O
N
N
O
b)
O
N
2p, 79%
O
2q
2p
98% (1.88 : 1)
Cl
Zn (7.6 equiv)
CH3COOH (3 mL)
N
O
N
F
120 °C, 6 h
O
N
O
N
O
N
2a
3a, 78%
N
N
O
c)
N
N
O
O
O
KOH aq. (4.5 M, 3 mL)
EtOH (10 mL)
COOH
2r, 81%
2t, 75%
O
2s, 78%
O
N
90 °C, 24 h
O
COOH
4a, 91%
O
N
O
N
N
N
2a
S
N
N
N
O
O
O
O
We next examined the effect of directing groups in direct
C-H carbonylation of N-(pyridin-2-ylmethyl)benzamides
and the results are summarized in Scheme 4. It was shown
that no reaction occurred when methyl (1a’) or benzyl
(1b’) as the directing group was employed. These findings
indicated that the coordination of the cobalt catalyst with
the N atom on the directing group was crucial in the
reaction. Notably, the reactions of 1c’ and 1d’ failed to
proceed, suggesting that the position of the N atom was
also important in the coordination of the Co catalyst.
Additionally, the reaction of the amide 1e’ bearing 8-
aminoquinoline as the directing group could give the
desired phthalimide in only 20% yield. Moreover, attempts
2w, 33%
2v, 51%
2u, 71%
aReaction condition: N-(pyridin-2-ylmethyl)benzamides 1
(0.3 mmol), TFBen (3.0 equiv), AcOH (2.0 equiv), Co(acac)2
(20 mol %), Ag2CO3 (2.0 equiv), 1,4-dioxane (2 mL), 130 º
C, 10 h, isolated yield. b150 ºC.
N-(pyridin-2-ylmethyl)benzamides bearing electron-
donating para-substituent could undergo the reaction
smoothly to give the desired products 2b-f in 35-95%
yields. Compounds with electron-withdrawing para-
substituent also showed good compatibilities, and the
corresponding products 2g-n were obtained in 31-90%
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on extending the substrates scope by modifying the complex C. Finally, reductive elimination of C affords the
1
2
3
4
5
6
7
8
carbonyl group all failed (Scheme 4, 1f’-1i’).
expected product 2a and releases the Co(I) species, which
is further oxidized by Ag(I) salt to regenerate the Co(II)
catalyst and completes the catalytic cycle.
Scheme 4. Effect of directing groups in C-H
carbonylation of N-(pyridin-2-ylmethyl)benzamides.
Co(acac)2 (20 mol %)
Scheme 6. Plausible Mechanism.
O
O
Ag2CO3 (2.0 equiv)
AcOH (2.0 equiv)
O
DG
N
N
DG
+
TFBen
(3.0 equiv.)
N
H
1,4-dioxane (2 mL)
130 °C, 10 h
H
N
O
2
1
1a
Ag0
9
O
O
O
CoIIX
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N
N
H
N
H
X = OAc
Ag0
H
-H+
N
1a', n.r.
O
1c', n.r.
1b', n.r.
AgI
O
X
O
O
O
S
CoIX
N
CoIII
N
N
N
H
N
N
H
N
O
N
X
A
2a
1e', 20%
HN
1d', n.r.
1f', n.r.
HN
C-H activation
AcOH
redutive
elimination
-H+
N
O
O
N
N
N
N
O
N
CoIII
1g', 5%
1i', trace
1h', trace
N
CoIII
N
X
X
O
In order to gain more insights into the reaction
mechanism, a few control experiments were conducted
(Scheme 5). When 1a was treated with the stoichiometric
amount of Co(acac)2 (1.0 equiv) in the absence of Ag2CO3
as the oxidant under standard conditions, the reaction
didn’t occur (Scheme 5, eq a). Interestingly, replacement of
Co(acac)2 with Co(acac)3 gave the expected product 2a in
18% yield. Meanwhile, 50% yield of 1a was recovered
(Scheme 5, eq b). These results indicated that the Co(III)
complex, generated in situ from oxidation of Co(II) by
Ag2CO3, was the active catalyst involved in direct C-H
carbonylation of N-(pyridin-2-ylmethyl)benzamides.
C
B
CO insertion
CO
TFBen
In conclusion, we have established a facile and efficient
approach for the synthesis of phthalimides via Co-
catalyzed direct C-H carbonylation of N-(pyridin-2-
ylmethyl)benzamides using 2-picolylamine as the directing
group and TFBen as the CO source. This method exhibits a
broad substrate scope with high functional group
compatibility, leading to various phthalimides in good
yields.
Scheme 5. Control Experiments.
EXPERIMENTAL SECTION
Co(acac)2 (1.0 equiv)
O
Unless otherwise noted, all reactions were carried out
under a nitrogen atmosphere. All reagents were obtained
from commercial sources and used as received without
further purification. Column chromatography was
performed on silica gel (200-300 mesh) using petroleum
ether (bp 60-90 °C) and ethyl acetate as eluent. Gas
chromatography (GC) analyses were performed on a
Shimadzu GC-2014C chromatograph equipped with FID
detector. 1H NMR spectra were taken on 400 MHz
instruments. Chemical shifts (in ppm) were calibrated with
tetramethylsilane (δ = 0.00 ppm) or DMSO (δ = 2.50 ppm).
The multiplicities of the signals were reported as s
(singlet), d (doublet), t (triplet), dd (doublet of doublets),
or m (multiplet), and coupling constants (J) were given in
hertz. 13C NMR spectra were obtained at 101 MHz and
were calibrated with CDCl3 (δ = 77.0 ppm) or DMSO (δ =
39.5 ppm).
AcOH (2.0 equiv)
N
H
TFBen
N.R.
+
a)
b)
1,4-dioxane (2 mL)
130 °C, 10 h
N
(3.0 equiv)
1a
O
O
Co(acac)3 (1.0 equiv)
AcOH (2.0 equiv)
N
+
N
H
TFBen
N
1,4-dioxane (2 mL)
130 °C, 10 h
O
N
(3.0 equiv)
2a, 18%
1a
1a, 50%
recovered
+
Based on the previous reports on cobalt
catalysis3b,3d,3e,4c,10 and our experimental results, a plausible
mechanism for the Co-catalyzed C-H carbonylation of N-
(pyridin-2-ylmethyl)benzamides is proposed as shown in
Scheme 6. Initially, the Co(II) catalyst coordinates with the
N-(pyridin-2-ylmethyl)benzamide 1a and is then oxidized
by Ag(I) salt to generate the Co(III) intermediate A. Under
the assistant of AcOH, ortho C-H activation of A gives the
Co(III) complex B. Then, coordination of CO, generated in
situ from TFBen, leads to the formation of the acyl Co(III)
Preparation of Benzene-1,3,5-triyl Triformate
(TFBen).9 Formic acid (8.4 mL, 222.8 mmol, 5.0 equiv)
was added to acetic anhydride (16.8 mL, 178.2 mmol, 4.0
equiv) at rt. The mixture was stirred at 60 °C for 1 h and
cooled to rt. The resulting solution was poured into a flask
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containing 1,3,5-trihydroxybenzene (5.62 g, 44.6 mmol, 1.0 1.7 Hz, 1H), 7.43 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 7.8 Hz, 1H),
1
2
3
4
5
6
7
8
7.18 (dd, J = 6.9, 5.3 Hz, 1H), 4.74 (d, J = 5.0 Hz, 2H), 1.32 (s,
9H). 13C{1H} NMR (101 MHz, CDCl3): δ 167.3, 156.5, 154.8,
148.8, 136.6, 131.4, 126.9, 125.3, 122.2, 122.0, 44.7, 34.8,
31.1.
equiv) and NaOAc (1.83 g, 22.3 mmol, 0.5 equiv). The
mixture was stirred for 4 h in a water bath and then
diluted with toluene (100 mL), washed with H2O (50 mL)
twice. Keep the organic phase in fridge (2-8 °C) for
overnight. Then filtered and dried in vacuo to afford the
desired product benzene-1,3,5-triyl triformate (TFBen)
(5.1 g, 55%) as a white solid. Mp: 53.2-55.6 °C. H NMR
(400 MHz, CDCl3): δ 8.24 (s, 3H), 6.97 (s, 3H). 13C{1H} NMR
(101 MHz, CDCl3): δ 158.1, 150.3, 112.6.
4-Methoxy-N-(pyridin-2-ylmethyl)benzamide, 1e.6 430.8
mg, 89% yield. White solid. Mp: 152.2-154.1 °C. Rf = 0.2
1
(EA). H NMR (400 MHz, CDCl3): δ 8.55 (d, J = 4.4 Hz, 1H),
1
7.85 (d, J = 8.8 Hz, 2H), 7.67 (td, J = 7.7, 1.6 Hz, 1H), 7.58 (s,
1H), 7.32 (d, J = 7.8 Hz, 1H), 7.24 – 7.17 (m, 1H), 6.93 (d, J =
8.8 Hz, 2H), 4.74 (d, J = 4.8 Hz, 2H), 3.84 (s, 3H). 13C{1H}
NMR (101 MHz, CDCl3): δ 166.9, 162.1, 156.5, 148.9, 136.7,
128.8, 126.7, 122.3, 122.1, 113.7, 55.3, 44.7.
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General Procedure for the Syntheses of N-(pyridin-2-
ylmethyl)benzamides. To a 100 mL single-neck flask
charged with CH2Cl2 (30 mL) were added 2-picolylamine
(10 mmol) and triethylamine (15 mmol). After stirring at
room temperature for 5 min, the reaction solution was
cooled in an ice bath. An acid chloride (11 mmol) was
added dropwise. Note that the solidified acid chloride
reagent needs to be dissolved firstly with CH2Cl2. Then the
reaction solution was stirred overnight to improve the
yield. The mixture was filtered through a pad of Celite, and
the residue was washed with CH2Cl2 (25 mL) subsequently.
The collected CH2Cl2 solution was washed with 1 M
NaHCO3 aqueous solution for three times. After that, the
organic layer was collected and dried over Na2SO4. The
solvent was removed by rotary-evaporation. The resulting
residue was purified by column chromatography
(petroleum ether / ethyl acetate = 1 / 1) to give the pure
amides.3 1b-w were synthesized following this procedure
in 2 mmol scale. 1a’ was obtained from Energy Chemical.
N-(Pyridin-2-ylmethyl)benzamide, 1a.6 1.87 g, 88% yield.
4-(Dimethylamino)-N-(pyridin-2-ylmethyl)benzamide, 1f.6
414.4 mg, 86% yield. White solid. Mp: 146.8-148.4 °C. Rf =
1
0.2 (EA). H NMR (400 MHz, CDCl3): δ 8.53 (d, J = 4.4 Hz,
1H), 7.78 (d, J = 8.9 Hz, 2H), 7.63 (td, J = 7.7, 1.7 Hz, 1H),
7.52 (s, 1H), 7.31 (d, J = 7.8 Hz, 1H), 7.20 – 7.13 (m, 1H),
6.67 – 6.63 (m, 2H), 4.72 (d, J = 5.0 Hz, 2H), 2.99 (s, 6H).
13C{1H} NMR (101 MHz, CDCl3): δ 167.3, 157.1, 152.4,
148.79, 136.6, 128.5, 122.1, 122.0, 121.1, 110.9, 44.7, 40.0.
4-Fluoro-N-(pyridin-2-ylmethyl)benzamide, 1g. 444.1 mg,
97% yield. Pale yellow solid. Mp: 78.9-80.2 °C. Rf = 0.25
1
(EA). H NMR (400 MHz, CDCl3): δ 8.55 (d, J = 4.5 Hz, 1H),
7.89 (dd, J = 8.2, 5.6 Hz, 2H), 7.78 (s, 1H), 7.68 (t, J = 7.7 Hz,
1H), 7.32 (d, J = 7.8 Hz, 1H), 7.25 – 7.18 (m, 1H), 7.10 (t, J =
8.5 Hz, 2H), 4.73 (d, J = 4.8 Hz, 2H). 13C{1H} NMR (101 MHz,
CDCl3): δ 166.3, 164.7 (d, J = 251.6 Hz), 156.1, 148.9, 136.8,
130.5, 129.4 (d, J = 8.9 Hz), 122.4, 122.2, 115.4 (d, J = 21.8
Hz), 44.7. HRMS (ESI-TOF): [M + H]+ calcd for C13H12FN2O+,
231.0928; found, 231.0951.
4-Chloro-N-(pyridin-2-ylmethyl)benzamide, 1h.6 452.8 mg,
92% yield. White solid. Mp: 102.3-104.2 °C. Rf = 0.2 (EA).
1H NMR (400 MHz, CDCl3): δ 8.54 (d, J = 4.4 Hz, 1H), 7.87 (s,
1H), 7.84 – 7.78 (m, 2H), 7.68 (td, J = 7.7, 1.7 Hz, 1H), 7.42 –
7.36 (m, 2H), 7.32 (d, J = 7.8 Hz, 1H), 7.25 – 7.19 (m, 1H),
4.73 (d, J = 4.9 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ
166.2, 156.0, 148.8, 137.6, 136.84, 132.6, 128.7, 128.5,
122.4, 122.2, 44.6.
1
Pale yellow solid. Mp: 67.6-69.8 °C. Rf = 0.25 (EA). H NMR
(400 MHz, CDCl3): δ 8.47 (d, J = 4.8 Hz, 1H), 8.19 (s, 1H),
7.91 – 7.83 (m, 2H), 7.58 (td, J = 7.7, 1.7 Hz, 1H), 7.43 (t, J =
7.3 Hz, 1H), 7.34 (t, J = 7.6 Hz, 2H), 7.25 (d, J = 7.8 Hz, 1H),
7.12 (dd, J = 7.1, 5.2 Hz, 1H), 4.69 (d, J = 5.2 Hz, 2H). 13C{1H}
NMR (101 MHz, CDCl3): δ 167.2, 156.5, 148.5, 136.5, 133.9,
131.1, 128.1, 126.8, 122.0, 121.6, 44.5.
4-Bromo-N-(pyridin-2-ylmethyl)benzamide, 1i.6 554.7 mg,
93% yield. White solid. Mp: 115.4-117.2 °C. Rf = 0.2 (EA).
1H NMR (400 MHz, CDCl3): δ 8.55 (d, J = 4.7 Hz, 1H), 7.79 (s,
1H), 7.77 – 7.73 (m, 2H), 7.68 (td, J = 7.7, 1.7 Hz, 1H), 7.56
(d, J = 8.5 Hz, 2H), 7.32 (d, J = 7.8 Hz, 1H), 7.22 (dd, J = 7.2,
5.2 Hz, 1H), 4.73 (d, J = 4.8 Hz, 2H). 13C{1H} NMR (101 MHz,
CDCl3): δ 166.3, 155.9, 148.9, 136.8, 133.2, 131.7, 128.7,
126.1, 122.5, 122.2, 44.7.
4-Methyl-N-(pyridin-2-ylmethyl)benzamide, 1b.6 433.5
mg, 96% yield. White solid. Mp: 101.4-103.1 °C. Rf = 0.2
1
(EA). H NMR (400 MHz, CDCl3): δ 8.53 (d, J = 4.5 Hz, 1H),
7.77 (d, J = 6.9 Hz, 3H), 7.65 (t, J = 7.7 Hz, 1H), 7.31 (d, J =
7.8 Hz, 1H), 7.19 (dd, J = 13.6, 7.0 Hz, 3H), 4.73 (d, J = 4.7
Hz, 2H), 2.38 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ
167.3, 156.5, 148.8, 141.7, 136.7, 131.4, 129.0, 127.0, 122.2,
122.0, 44.7, 21.3.
N-(Pyridin-2-ylmethyl)-4-(trifluoromethyl)benzamide,
4-Ethyl-N-(pyridin-2-ylmethyl)benzamide, 1c. 436.9 mg,
91% yield. Pale yellow solid. Mp: 55.9-57.5 °C. Rf = 0.2 (EA).
1H NMR (400 MHz, CDCl3): δ 8.51 (d, J = 4.7 Hz, 1H), 7.85 (s,
1H), 7.80 (d, J = 8.1 Hz, 2H), 7.63 (td, J = 7.7, 1.5 Hz, 1H),
7.29 (d, J = 7.8 Hz, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.19 – 7.14
(m, 1H), 4.72 (d, J = 5.0 Hz, 2H), 2.66 (q, J = 7.6 Hz, 2H),
1.23 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ
167.3, 156.6, 148.8, 147.9, 136.6, 131.6, 127.8, 127.1, 122.1,
121.9, 44.6, 28.6, 15.1. HRMS (ESI-TOF): [M + H]+ calcd for
C15H17N2O+, 241.1335; found, 241.1348.
1j.12 476.3 mg, 85% yield. White solid. Mp: 104.1-106.3 °C.
1
Rf = 0.25 (EA). H NMR (400 MHz, CDCl3): δ 8.55 (d, J = 4.4
Hz, 1H), 8.02 (s, 1H), 7.98 (d, J = 8.1 Hz, 2H), 7.69 (ddd, J =
8.2, 6.6, 2.6 Hz, 3H), 7.34 (d, J = 7.8 Hz, 1H), 7.23 (dd, J = 6.9,
5.3 Hz, 1H), 4.76 (d, J = 4.8 Hz, 2H). 13C{1H} NMR (101 MHz,
CDCl3): δ 166.0, 155.8, 148.9, 137.6, 136.9, 133.1 (q, J =
32.7 Hz), 127.5, 125.5 (d, J = 3.1 Hz), 123.7 (q, J = 272.4 Hz),
122.5, 122.2, 44.7.
N-(Pyridin-2-ylmethyl)-4-(trifluoromethoxy)benzamide,
1k. 533.0 mg, 90% yield. White solid. Mp: 93.4-95.1 °C. Rf =
4-(tert-Butyl)-N-(pyridin-2-ylmethyl)benzamide,
1d.11
1
0.2 (EA). Rf = 0.25 (EA). H NMR (400 MHz, CDCl3): δ 8.53
499.4 mg, 93% yield. White solid. Mp: 111.2-112.6 °C. Rf =
(d, J = 4.6 Hz, 1H), 8.02 (s, 1H), 7.92 (d, J = 8.7 Hz, 2H), 7.67
(td, J = 7.7, 1.6 Hz, 1H), 7.32 (d, J = 7.8 Hz, 1H), 7.22 (dd, J =
12.8, 8.0 Hz, 3H), 4.73 (d, J = 4.8 Hz, 2H). 13C{1H} NMR (101
1
0.2 (EA). H NMR (400 MHz, CDCl3): δ 8.53 (d, J = 4.4 Hz,
1H), 7.82 (d, J = 8.5 Hz, 2H), 7.78 (s, 1H), 7.64 (td, J = 7.7,
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MHz, CDCl3): δ 166.0, 156.1, 151.4, 148.9, 136.8, 132.7,
3H). 13C{1H} NMR (101 MHz, CDCl3): δ 169.9, 156.2, 148.9,
136.7, 136.1, 130.9, 129.7, 126.9, 125.6, 122.3, 122.0, 44.6,
19.8.
1
2
128.9, 122.4, 122.1, 120.4, 120.2 (q, J = 258.3 Hz), 44.7.
+
HRMS (ESI-TOF): [M + H]+ calcd for C14H12F3N2O2 ,
297.0845; found, 297.0860.
2-Fluoro-N-(pyridin-2-ylmethyl)benzamide, 1s. 432.0 mg,
94% yield. Pale yellow solid. Mp: 55.4-57.2 °C. Rf = 0.25
(EA). H NMR (400 MHz, CDCl3): δ 8.57 (d, J = 4.3 Hz, 1H),
3
4
5
6
7
8
9
4-Cyano-N-(pyridin-2-ylmethyl)benzamide, 1l.6 445.2 mg,
94% yield. White solid. Mp: 135.1-137.6 °C. Rf = 0.25 (EA).
1H NMR (400 MHz, CDCl3): δ 8.52 (d, J = 4.5 Hz, 1H), 8.32 (s,
1H), 7.98 (d, J = 8.3 Hz, 2H), 7.70 (dd, J = 10.4, 4.9 Hz, 3H),
7.33 (d, J = 7.8 Hz, 1H), 7.23 (dd, J = 7.0, 5.3 Hz, 1H), 4.73 (d,
J = 5.0 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ 165.4,
155.7, 148.7, 137.9, 136.7, 132.0, 127.6, 122.3, 121.9, 117.8,
114.6, 44.6.
1
8.11 (td, J = 7.9, 1.7 Hz, 1H), 8.04 (s, 1H), 7.67 (td, J = 7.7,
1.6 Hz, 1H), 7.50 – 7.43 (m, 1H), 7.33 (d, J = 7.8 Hz, 1H),
7.28 – 7.18 (m, 2H), 7.13 (dd, J = 11.8, 8.4 Hz, 1H), 4.80 (d, J
= 4.9 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ 163.24 (d, J
= 2.8 Hz), 160.62 (d, J = 248.3 Hz), 156.1, 149.0, 136.6,
133.1 (d, J = 9.2 Hz), 131.8, 124.53 (d, J = 3.0 Hz), 122.2,
121.8, 121.0 (d, J = 11.4 Hz), 115.9 (d, J = 24.5 Hz), 45.0.
HRMS (ESI-TOF): [M + H]+ calcd for C13H12FN2O+, 231.0928;
found, 231.0951.
2-Chloro-N-(pyridin-2-ylmethyl)benzamide, 1t. 437.9 mg,
89% yield. Pale yellow solid. Mp: 96.0-97.8 °C. Rf = 0.2 (EA).
1H NMR (400 MHz, CDCl3): δ 8.49 (d, J = 4.7 Hz, 1H), 7.66
(ddd, J = 13.3, 7.5, 1.6 Hz, 3H), 7.41 – 7.26 (m, 4H), 7.19 (dd,
J = 6.9, 5.4 Hz, 1H), 4.75 (d, J = 5.0 Hz, 2H). 13C{1H} NMR
(101 MHz, CDCl3): δ 166.5, 155.9, 148.8, 136.7, 135.0,
131.0, 130.8, 130.0, 129.8, 126.8, 122.3, 121.9, 44.9. HRMS
(ESI-TOF): [M + H]+ calcd for C13H12ClN2O+, 247.0633;
found, 247.0649.
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Methyl 4-((pyridin-2-ylmethyl)carbamoyl)benzoate, 1m.6
517.0 mg, 96% yield. White solid. Mp: 104.1-105.3 °C. Rf =
1
0.2 (EA). H NMR (400 MHz, CDCl3): δ 8.55 (d, J = 4.7 Hz,
1H), 8.09 (d, J = 8.3 Hz, 2H), 7.93 (d, J = 8.3 Hz, 3H), 7.69 (td,
J = 7.7, 1.6 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.22 (dd, J = 7.0,
5.3 Hz, 1H), 4.75 (d, J = 4.8 Hz, 2H), 3.93 (s, 3H). 13C{1H}
NMR (101 MHz, CDCl3): δ 166.4, 166.2, 155.9, 148.9, 138.2,
136.8, 132.6, 129.7, 127.1, 122.4, 122.1, 52.3, 44.7.
4-Nitro-N-(pyridin-2-ylmethyl)benzamide, 1n. 396.8 mg,
77% yield. Pale yellow solid. Mp: 135.7-137.6 °C. Rf = 0.2
1
(EA). H NMR (400 MHz, CDCl3): δ 8.56 (d, J = 4.7 Hz, 1H),
8.33 – 8.25 (m, 2H), 8.08 – 8.04 (m, 2H), 8.02 (s, 1H), 7.72
(td, J = 7.7, 1.7 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 7.26 (dd, J =
7.0, 5.4 Hz, 1H), 4.77 (d, J = 4.7 Hz, 2H). 13C{1H} NMR (101
MHz, CDCl3): δ 165.2, 155.3, 149.6, 148.9, 139.9, 137.0,
128.3, 123.7, 122.6, 122.2, 44.7. HRMS (ESI-TOF): [M + H]+
3,5-Dimethyl-N-(pyridin-2-ylmethyl)benzamide, 1u. 426.3
mg, 89% yield. Pale yellow solid. Mp: 74.8-76.6 °C. Rf = 0.2
1
(EA). H NMR (400 MHz, CDCl3): δ 8.53 (d, J = 4.7 Hz, 1H),
7.76 (s, 1H), 7.63 (dd, J = 11.3, 4.0 Hz, 1H), 7.47 (s, 2H),
7.30 (d, J = 7.8 Hz, 1H), 7.21 – 7.15 (m, 1H), 7.10 (s, 1H),
4.72 (d, J = 5.0 Hz, 2H), 2.32 (s, 6H). 13C{1H} NMR (101 MHz,
CDCl3): δ 167.7, 156.6, 148.8, 138.0, 136.6, 134.2, 132.9,
124.7, 122.2, 121.9, 44.7, 21.0. HRMS (ESI-TOF): [M + H]+
calcd for C15H17N2O+, 241.1335; found, 241.1354.
+
calcd for C13H12N3O3 , 258.0873; found, 258.0893.
N-(Pyridin-2-ylmethyl)-[1,1'-biphenyl]-4-carboxamide,
1o.13 535.8 mg, 93% yield. White solid. Mp: 144.6-146.8 °C.
1
Rf = 0.25 (EA). H NMR (400 MHz, CDCl3): δ 8.55 (d, J = 4.7
Hz, 1H), 7.95 (d, J = 8.2 Hz, 2H), 7.85 (s, 1H), 7.64 (ddd, J =
25.4, 12.5, 4.3 Hz, 5H), 7.44 (t, J = 7.6 Hz, 2H), 7.35 (dd, J =
20.7, 7.4 Hz, 2H), 7.22 – 7.15 (m, 1H), 4.76 (d, J = 4.9 Hz,
2H). 13C{1H} NMR (101 MHz, CDCl3): δ 167.0, 156.3, 148.9,
144.1, 140.0, 136.7, 132.9, 128.8, 127.8, 127.6, 127.1, 122.3,
122.1, 44.7.
3,5-Dimethoxy-N-(pyridin-2-ylmethyl)benzamide,
1v.6
495.5 mg, 91% yield. Pale yellow solid. Mp: 91.9-93.1 °C. Rf
1
= 0.2 (EA). H NMR (400 MHz, CDCl3): δ 8.54 (d, J = 4.7 Hz,
1H), 7.73 (s, 1H), 7.67 (td, J = 7.7, 1.7 Hz, 1H), 7.32 (d, J =
7.8 Hz, 1H), 7.20 (dd, J = 6.9, 5.3 Hz, 1H), 7.01 (d, J = 2.2 Hz,
2H), 6.57 (t, J = 2.2 Hz, 1H), 4.73 (d, J = 4.9 Hz, 2H), 3.80 (s,
6H). 13C{1H} NMR (101 MHz, CDCl3): δ 167.1, 160.7, 156.3,
148.9, 136.7, 136.4, 122.3, 122.1, 104.9, 103.6, 55.4, 44.8.
N-(Pyridin-2-ylmethyl)-1-naphthamide, 1p.12 492.7 mg,
94% yield. Pale yellow solid. Mp: 115.2-117.8 °C. Rf = 0.2
1
(EA). H NMR (400 MHz, CDCl3): δ 8.47 (d, J = 4.3 Hz, 1H),
8.40 – 8.34 (m, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.83 (dd, J = 6.5,
3.0 Hz, 1H), 7.68 – 7.61 (m, 2H), 7.54 – 7.45 (m, 3H), 7.41
(dd, J = 8.2, 7.1 Hz, 1H), 7.32 (d, J = 7.8 Hz, 1H), 7.16 (dd, J =
7.0, 5.4 Hz, 1H), 4.80 (d, J = 5.0 Hz, 2H). 13C{1H} NMR (101
MHz, CDCl3): δ 169.5, 156.2, 148.9, 136.7, 134.2, 133.6,
130.5, 130.2, 128.1, 126.9, 126.2, 125.5, 125.1, 124.6, 122.3,
121.9, 44.8.
N-(Pyridin-2-ylmethyl)thiophene-2-carboxamide,
1w.
421.2 mg, 97% yield. White solid. Mp: 76,4-78.2 °C. Rf =
1
0.25 (EA). H NMR (400 MHz, CDCl3): δ 8.51 (d, J = 4.8 Hz,
1H), 7.96 (s, 1H), 7.69 – 7.58 (m, 2H), 7.47 – 7.38 (m, 1H),
7.31 (d, J = 8.1 Hz, 1H), 7.18 (dd, J = 7.2, 5.2 Hz, 1H), 7.02
(dd, J = 4.9, 3.8 Hz, 1H), 4.69 (d, J = 5.2 Hz, 2H). 13C{1H}
NMR (101 MHz, CDCl3): δ 161.9, 156.4, 148.8, 138.8, 136.7,
129.8, 128.1, 127.4, 122.3, 122.0, 44.6. HRMS (ESI-TOF):
[M + H]+ calcd for C11H11N2OS+, 219.0587; found, 219.0604.
N-Benzylbenzamide, 1b’.6 363.2 mg, 86% yield. White
solid. Mp: 104.4-106.1 °C. Rf = 0.2 (EA). 1H NMR (400 MHz,
CDCl3): δ 7.77 (d, J = 7.6 Hz, 2H), 7.45 (t, J = 6.8 Hz, 1H),
7.38 – 7.22 (m, 7H), 6.94 (s, 1H), 4.56 (d, J = 5.6 Hz, 2H).
13C{1H} NMR (101 MHz, CDCl3): δ 167.4, 138.2, 134.3,
131.4, 128.6, 128.4, 127.7, 127.3, 126.9, 43.9.
N-(Pyridin-2-ylmethyl)-2-naphthamide, 1q.14 476.9 mg,
91% yield. Pale yellow solid. Mp: 74.8-76.3 °C. Rf = 0.2 (EA).
1H NMR (400 MHz, CDCl3): δ 8.54 (d, J = 4.5 Hz, 1H), 8.38 (s,
1H), 8.04 (s, 1H), 7.92 (dd, J = 8.5, 1.6 Hz, 1H), 7.88 – 7.77
(m, 3H), 7.62 (td, J = 7.7, 1.7 Hz, 1H), 7.54 – 7.44 (m, 2H),
7.30 (d, J = 7.8 Hz, 1H), 7.16 (dd, J = 7.0, 5.3 Hz, 1H), 4.78 (d,
J = 5.0 Hz, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ 167.4,
156.4, 148.8, 136.7, 134.6, 132.5, 131.4, 128.8, 128.2, 127.5,
127.4, 126.5, 123.6, 122.3, 122.0, 44.8.
N-(Pyridin-3-ylmethyl)benzamide, 1c’.15 381.8 mg, 90%
2-Methyl-N-(pyridin-2-ylmethyl)benzamide, 1r.6 446.3 mg,
99% yield. Pale yellow solid. Mp: 63.6-64.9 °C. Rf = 0.2 (EA).
1H NMR (400 MHz, CDCl3): δ 8.49 (d, J = 4.7 Hz, 1H), 7.66
(td, J = 7.7, 1.7 Hz, 1H), 7.44 (d, J = 7.7 Hz, 1H), 7.35 – 7.26
(m, 3H), 7.23 – 7.16 (m, 3H), 4.71 (d, J = 5.0 Hz, 2H), 2.45 (s,
yield. Pale yellow solid. Mp: 66.5-67.4 °C. Rf = 0.2 (EA). H
1
NMR (400 MHz, CDCl3): δ 8.40 (d, J = 1.6 Hz, 1H), 8.36 (dd, J
= 4.8, 1.3 Hz, 1H), 8.14 (s, 1H), 7.81 (d, J = 7.3 Hz, 2H), 7.59
(d, J = 7.9 Hz, 1H), 7.43 (t, J = 7.4 Hz, 1H), 7.32 (t, J = 7.7 Hz,
2H), 7.14 (dd, J = 7.8, 4.9 Hz, 1H), 4.51 (d, J = 5.9 Hz, 2H).
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13C{1H} NMR (101 MHz, CDCl3): δ 167.8, 148.7, 148.2,
4.6 Hz, 1H), 7.74 (d, J = 7.6 Hz, 1H), 7.67 (s, 1H), 7.62 (td, J
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135.4, 134.2, 133.8, 131.4, 128.2, 127.0, 123.4, 41.1.
= 7.7, 1.7 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.26 (d, J = 7.8 Hz,
1H), 7.15 (dd, J = 7.2, 5.1 Hz, 1H), 5.00 (s, 2H), 2.50 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3): δ 168.1, 168.0, 155.3,
149.4, 145.2, 136.5, 134.4, 132.4, 129.4, 123.8, 123.2, 122.3,
121.3, 42.7, 21.8.
N-(Pyridin-2-yl)benzamide, 1d’.6 344.7 mg, 87% yield.
1
White solid. Mp: 87.3-88.6 °C. Rf = 0.3 (PE/EA = 2/1). H
NMR (400 MHz, CDCl3): δ 9.52 (s, 1H), 8.42 (d, J = 8.4 Hz,
1H), 8.04 (dd, J = 4.9, 1.0 Hz, 1H), 7.96 – 7.91 (m, 2H), 7.75
– 7.68 (m, 1H), 7.56 – 7.50 (m, 1H), 7.44 (dd, J = 10.4, 4.7
Hz, 2H), 6.98 (ddd, J = 7.3, 5.0, 0.8 Hz, 1H). 13C{1H} NMR
(101 MHz, CDCl3): δ 166.1, 151.7, 147.6, 138.3, 134.4,
132.0, 128.6, 127.3, 119.7, 114.3.
5-Ethyl-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione, 2c.
67.9 mg, 85% yield. White solid. Mp: 88.3-90.4 °C. Rf = 0.5
(PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.54 – 8.49 (m,
1H), 7.78 (dd, J = 7.6, 1.5 Hz, 1H), 7.71 (s, 1H), 7.66 – 7.59
(m, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.27 (d, J = 7.8 Hz, 1H),
7.18 – 7.12 (m, 1H), 5.00 (s, 2H), 2.80 (q, J = 7.6 Hz, 2H),
1.29 (td, J = 7.6, 1.8 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3):
δ 168.2, 168.1, 155.4, 151.5, 149.5, 136.5, 133.5, 132.5,
129.7, 123.4, 122.8, 122.3, 121.4, 42.8, 29.2, 15.1. HRMS
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N-(Quinolin-8-yl)benzamide, 1e’.3 421.7 mg, 85% yield.
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1
White solid. Mp: 81.7-82.9 °C. Rf = 0.3 (PE/EA = 2/1). H
NMR (400 MHz, CDCl3): δ 10.70 (s, 1H), 8.92 (dd, J = 7.6,
1.0 Hz, 1H), 8.78 (dd, J = 4.2, 1.5 Hz, 1H), 8.08 (ddd, J = 9.4,
8.2, 1.6 Hz, 3H), 7.50 (tdd, J = 9.3, 8.2, 3.4 Hz, 5H), 7.39 (dd,
J = 8.3, 4.2 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3): δ 165.2,
148.1, 138.6, 136.2, 135.0, 134.4, 131.7, 128.6, 127.8, 127.3,
127.1, 121.5, 116.4.
+
(ESI-TOF): [M + H]+ calcd for C16H15N2O2 , 267.1128; found,
267.1139.
5-(tert-Butyl)-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione,
2d. 80.6 mg, 91% yield. White solid. Mp: 105.1-106.9 °C. Rf
= 0.5 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.51 (d, J
= 4.3 Hz, 1H), 7.92 (d, J = 0.7 Hz, 1H), 7.80 (d, J = 7.9 Hz,
1H), 7.75 (dd, J = 7.9, 1.4 Hz, 1H), 7.62 (td, J = 7.7, 1.6 Hz,
1H), 7.27 (d, J = 7.8 Hz, 1H), 7.15 (dd, J = 7.3, 5.1 Hz, 1H),
5.01 (s, 2H), 1.37 (s, 9H). 13C{1H} NMR (101 MHz, CDCl3): δ
168.4, 167.9, 158.5, 155.4, 149.4, 136.5, 132.2, 130.8, 129.4,
123.1, 122.1, 121.3, 120.5, 42.7, 35.6, 31.0. HRMS (ESI-
General Procedure for Carbonylative Synthesis of
Phthalimides from N-(pyridin-2-ylmethyl)benzamides.
To the ex-tube (15 mL) of an oven-dried In-Ex tube,
benzamide 1 (0.3 mmol, 1.0 equiv), Co(acac)2 (15.4 mg,
0.06 mmol, 20 mol %), Ag2CO3 (165.5 mg, 0.6 mmol, 2.0
equiv), and a stirring bar was added. In the in-tube (2.5
mL), TFBen (189.0 mg, 0.9 mmol, 3.0 equiv.) was added
tube. Then the In-Ex tube was placed under vacuum and
refilled with nitrogen three times. AcOH (36.0 mg, 0.6
mmol, 2.0 equiv.) and 1,4-dioxane (2.0 mL) were added
into the ex-tube via syringe. The In-Ex tube was sealed and
stirred at 130 °C in oil bath for 10 h. Upon the reaction was
completed, the resulting mixture was filtered through a
pad of tripolite and washed with EtOAc. The filtrate was
concentrated under vacuum and purified by silica gel
column using chromatography (petroleum ether/ethyl
acetate = 2/1) to obtain the product 2.
Procedure for 1.06 gram scale: To the ex-tube (100 mL)
of an oven-dried In-Ex tube, benzamide 1a (1.06 g, 5.0
mmol, 1.0 equiv), Co(acac)2 (257.2 mg, 1.0 mmol, 20
mol %), Ag2CO3 (2.76 g, 10.0 mmol, 2.0 equiv.), and a
stirring bar was added. In the in-tube (15 mL), TFBen (2.10
g, 10.0 mmol, 2.0 equiv) was added tube. Then the In-Ex
tube was placed under vacuum and refilled with nitrogen
three times. AcOH (600.5 mg, 10.0 mmol, 2.0 equiv) and
1,4-dioxane (33 mL) were added into the ex-tube via
syringe. The In-Ex tube was sealed and stirred at 130 °C in
oil bath for 10 h. Upon the reaction was completed, the
resulting mixture was filtered through a pad of tripolite
and washed with EtOAc. The filtrate was concentrated
under vacuum and purified by silica gel column using
chromatography (petroleum ether/ethyl acetate = 2/1) to
obtain the product 2a in 81% yield (0.96 g).
+
TOF): [M + H]+ calcd for C18H19N2O2 , 295.1441; found,
295.1463.
5-Methoxy-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione,
2e.6 72.4 mg, 90% yield. White solid. Mp: 134.1-135.2 °C. Rf
= 0.3 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.51 (d, J
= 4.7 Hz, 1H), 7.76 (d, J = 8.3 Hz, 1H), 7.62 (td, J = 7.7, 1.2
Hz, 1H), 7.34 (d, J = 2.1 Hz, 1H), 7.26 (d, J = 7.8 Hz, 1H),
7.18 – 7.13 (m, 2H), 4.98 (s, 2H), 3.91 (s, 3H). 13C{1H} NMR
(101 MHz, CDCl3): δ 167.7, 167.7, 164.5, 155.4, 149.4,
136.5, 134.6, 125.0, 123.9, 122.2, 121.3, 119.6, 108.1, 55.9,
42.8.
5-(Dimethylamino)-2-(pyridin-2-ylmethyl)isoindoline-1,3-
dione, 2f.6 29.9 mg, 35% yield. Yellow solid. Mp: 155.1-
1
156.3 °C. Rf = 0.25 (PE/EA = 2/1). H NMR (400 MHz,
CDCl3): δ 8.52 (d, J = 4.4 Hz, 1H), 7.66 (d, J = 8.5 Hz, 1H),
7.61 (td, J = 7.7, 1.6 Hz, 1H), 7.24 (d, J = 7.8 Hz, 1H), 7.14
(dd, J = 6.9, 5.3 Hz, 1H), 7.09 (d, J = 2.2 Hz, 1H), 6.80 (dd, J =
8.5, 2.3 Hz, 1H), 4.97 (s, 2H), 3.10 (s, 6H). 13C{1H} NMR
(101 MHz, CDCl3): δ 168.8, 168.3, 156.0, 154.3, 149.4,
136.5, 134.7, 124.8, 122.1, 121.2, 117.5, 114.6, 105.7, 42.7,
40.3.
5-Fluoro-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione, 2g.
69.3mg, 90% yield. Pale yellow solid. Mp: 144.8-146.7 °C.
Rf = 0.5 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.50 (d,
J = 4.4 Hz, 1H), 7.88 (dd, J = 8.2, 4.5 Hz, 1H), 7.64 (td, J = 7.7,
1.7 Hz, 1H), 7.55 (dd, J = 7.0, 2.2 Hz, 1H), 7.40 (td, J = 8.6,
2.3 Hz, 1H), 7.28 (d, J = 7.8 Hz, 1H), 7.16 (dd, J = 7.1, 5.2 Hz,
1H), 5.01 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ 166.9,
166.6, 166.2 (d, J = 256.9 Hz), 164.98, 154.9, 149.5, 136.5,
134.9 (d, J = 9.4 Hz), 127.9, 125.7 (d, J = 9.3 Hz), 122.40,
121.44, 120.9 (d, J = 23.6 Hz), 111.1 (d, J = 24.8 Hz), 42.9.
2-(Pyridin-2-ylmethyl)isoindoline-1,3-dione, 2a.6 63.1 mg,
88% yield. White solid. Mp: 122.2-124.1 °C. Rf = 0.5 (PE/EA
= 2/1). 1H NMR (400 MHz, CDCl3): δ 8.51 (d, J = 4.6 Hz, 1H),
7.86 (dt, J = 6.9, 3.5 Hz, 2H), 7.75 – 7.69 (m, 2H), 7.63 (td, J
= 7.7, 1.7 Hz, 1H), 7.28 (d, J = 7.8 Hz, 1H), 7.15 (dd, J = 7.1,
5.2 Hz, 1H), 5.02 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ
167.9, 155.2, 149.4, 136.5, 133.9, 132.0, 123.3, 122.3, 121.4,
42.7.
+
HRMS (ESI-TOF): [M + H]+ calcd for C14H10FN2O2 ,
257.0721; found, 257.0739.
5-Methyl-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione, 2b.6
72.0 mg, 95% yield. White solid. Mp: 104.7-105.8 °C. Rf =
0.5 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.51 (d, J =
5-Chloro-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione, 2h.6
73.8 mg, 90% yield. Mp: 136.4-137.8 °C. Rf = 0.5 (PE/EA =
1
2/1). White solid. H NMR (400 MHz, CDCl3): δ 8.50 (d, J =
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The Journal of Organic Chemistry
Page 8 of 10
4.2 Hz, 1H), 7.82 (dd, J = 9.7, 4.7 Hz, 2H), 7.69 (dd, J = 8.0,
(PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.53 (d, J = 4.3
1
2
3
4
5
6
7
8
1.7 Hz, 1H), 7.64 (td, J = 7.7, 1.7 Hz, 1H), 7.31 – 7.26 (m,
1H), 7.16 (dd, J = 6.9, 5.1 Hz, 1H), 5.00 (s, 2H). 13C{1H} NMR
(101 MHz, CDCl3): δ 167.0, 166.6, 154.8, 149.5, 140.5,
136.5, 133.9, 133.7, 130.1, 124.6, 123.7, 122.4, 121.4, 42.9.
5-Bromo-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione, 2i.6
72.0 mg, 76% yield. White solid. Mp: 133.5-135.6 °C. Rf =
0.5 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.51 (d, J =
4.5 Hz, 1H), 8.01 (d, J = 1.4 Hz, 1H), 7.87 (dd, J = 7.9, 1.6 Hz,
1H), 7.74 (d, J = 7.9 Hz, 1H), 7.64 (td, J = 7.7, 1.7 Hz, 1H),
7.28 (d, J = 7.8 Hz, 1H), 7.17 (dd, J = 7.2, 5.1 Hz, 1H), 5.01 (s,
2H). 13C{1H} NMR (101 MHz, CDCl3): δ 167.2, 166.7, 154.8,
149.5, 136.9, 136.7, 133.8, 130.7, 128.9, 126.8, 124.8, 122.5,
121.5, 43.0.
Hz, 1H), 8.08 (s, 1H), 7.92 (d, J = 1.0 Hz, 2H), 7.67 – 7.61 (m,
3H), 7.52 – 7.41 (m, 3H), 7.30 (d, J = 7.8 Hz, 1H), 7.17 (dd, J
= 7.1, 5.2 Hz, 1H), 5.04 (s, 2H). 13C{1H} NMR (101 MHz,
CDCl3): δ 168.0, 167.9, 155.3, 149.5, 147.4, 139.0, 136.7,
133.0, 132.5, 130.6, 129.1, 128.8, 127.2, 123.8, 122.4, 122.0,
121.5, 42.9. HRMS (ESI-TOF): [M + H]+ calcd for
+
C20H15N2O2 , 315.1128; found, 315.1149.
2-(Pyridin-2-ylmethyl)-1H-benzo[e]isoindole-1,3(2H)-
dione, 2p. 68.5 mg, 79% yield. White solid. Mp: 137.4-
139.6 °C. Rf = 0.5 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3):
δ 8.89 (d, J = 8.3 Hz, 1H), 8.53 (d, J = 4.5 Hz, 1H), 8.12 (d, J =
8.2 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 8.2 Hz, 1H),
7.69 – 7.59 (m, 3H), 7.32 (d, J = 7.8 Hz, 1H), 7.15 (dd, J = 7.2,
5.1 Hz, 1H), 5.04 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ
169.2, 168.6, 155.5, 149.5, 136.6, 136.5, 134.9, 131.3, 129.3,
128.6, 128.5, 127.9, 127.4, 124.9, 122.4, 121.5, 118.5, 42.7.
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2-(Pyridin-2-ylmethyl)-5-(trifluoromethyl)isoindoline-1,3-
dione, 2j. 69.9 mg, 76% yield. White solid. Mp: 98.2-99.8 °C.
Rf = 0.3 (PE/EA = 5/1). 1H NMR (400 MHz, CDCl3): δ 8.50 (d,
J = 4.6 Hz, 1H), 8.14 (s, 1H), 8.02 (d, J = 0.9 Hz, 2H), 7.65 (td,
J = 7.7, 1.7 Hz, 1H), 7.31 (d, J = 7.9 Hz, 1H), 7.18 (dd, J = 7.2,
5.0 Hz, 1H), 5.05 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ
166.7, 166.5, 154.6, 149.5, 136.6, 136.0 (q, J = 33.4 Hz),
135.0, 132.8, 131.1, 124.0, 123.0 (q, J = 272.7 Hz), 122.6,
121.6, 120.6, 43.0. HRMS (ESI-TOF): [M + H]+ calcd for
+
HRMS (ESI-TOF): [M + H]+ calcd for C18H13N2O2 , 289.0972;
found, 289.0992.
2-(Pyridin-2-ylmethyl)-1H-benzo[f]isoindole-1,3(2H)-
dione, 2q. 55.3 mg, 64% yield. White solid. Mp: 198.7-
200.4 °C. Rf = 0.4 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3):
δ 8.53 (d, J = 4.5 Hz, 1H), 8.35 (s, 2H), 8.04 (dd, J = 5.9, 3.2
Hz, 2H), 7.70 – 7.61 (m, 3H), 7.31 (d, J = 7.8 Hz, 1H), 7.19 –
7.13 (m, 1H), 5.08 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3): δ
167.7, 155.2, 149.5, 136.6, 135.4, 130.2, 129.1, 127.7, 124.8,
122.4, 121.5, 43.1. HRMS (ESI-TOF): [M + H]+ calcd for
+
C15H10F3N2O2 , 307.0689; found, 307.0705.
2-(Pyridin-2-ylmethyl)-5-(trifluoromethoxy)isoindoline-
1,3-dione, 2k.6 86.1 mg, 89% yield. White solid. Mp: 104.3-
106.1 °C. Rf = 0.5 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3):
δ 8.50 (d, J = 4.3 Hz, 1H), 8.00 – 7.89 (m, 1H), 7.72 (s, 1H),
7.64 (td, J = 7.7, 1.6 Hz, 1H), 7.55 (d, J = 8.1 Hz, 1H), 7.29 (d,
J = 7.9 Hz, 1H), 7.16 (dd, J = 6.9, 5.4 Hz, 1H), 5.02 (s, 2H).
13C{1H} NMR (101 MHz, CDCl3): δ 166.7, 166.4, 154.7,
153.3, 149.5, 136.5, 134.4, 130.0, 125.9, 125.3, 122.4, 121.5,
120.1 (q, J = 262.6 Hz), 115.6, 43.0.
+
C18H13N2O2 , 289.0972; found, 289.0992.
4-Methyl-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione, 2r.6
61.3 mg, 81% yield. White solid. Mp: 102.3-103.5. °C. Rf =
0.5 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.52 (d, J =
4.2 Hz, 1H), 7.69 (d, J = 7.3 Hz, 1H), 7.63 (td, J = 7.7, 1.8 Hz,
1H), 7.57 (t, J = 7.5 Hz, 1H), 7.46 (d, J = 7.7 Hz, 1H), 7.28 (d,
J = 7.9 Hz, 1H), 7.15 (dd, J = 7.0, 5.2 Hz, 1H), 4.99 (s, 2H),
2.69 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ 168.7, 168.0,
155.4, 149.5, 138.0, 136.5, 136.3, 133.4, 132.4, 128.7, 122.3,
121.4, 120.9, 42.7, 17.5.
1,3-Dioxo-2-(pyridin-2-ylmethyl)isoindoline-5-
carbonitrile, 2l.6 53.8 mg, 68% yield. White solid. Mp:
1
165.5-166.9 °C. Rf = 0.4 (PE/EA = 2/1). H NMR (400 MHz,
CDCl3): δ 8.48 (d, J = 4.6 Hz, 1H), 8.16 (s, 1H), 8.04 (q, J =
7.7 Hz, 2H), 7.66 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 7.7 Hz, 1H),
7.18 (dd, J = 7.3, 5.1 Hz, 1H), 5.04 (s, 2H). 13C{1H} NMR (101
MHz, CDCl3): δ 166.2, 165.9, 154.2, 149.5, 137.7, 136.6,
135.1, 132.7, 126.7, 124.1, 122.6, 121.6, 117.6, 116.9, 43.0.
4-Fluoro-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione, 2s.
60.1 mg, 78% yield. White solid. Mp: 131.4-133.1 °C. Rf =
0.5 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.51 (d, J =
4.7 Hz, 1H), 7.78 – 7.62 (m, 3H), 7.39 (t, J = 8.4 Hz, 1H),
7.30 (d, J = 8.5 Hz, 1H), 7.20 – 7.15 (m, 1H), 5.00 (s, 2H).
13C{1H} NMR (101 MHz, CDCl3): δ 166.9, 164.7, 157.5 (d, J =
265.9 Hz), 154.8, 149.5, 136.6, 136.5, 134.3, 122.5, 122.4 (d,
J = 20.3 Hz), 121.6, 119.6 (d, J = 3.4 Hz), 117.9 (d, J = 12.4
Methyl
1,3-dioxo-2-(pyridin-2-ylmethyl)isoindoline-5-
carboxylate, 2m.6 46.3 mg, 52% yield. White solid. Mp:
1
126.6-128.3 °C. Rf = 0.4 (PE/EA = 2/1). H NMR (400 MHz,
CDCl3): δ 8.51 (d, J = 3.3 Hz, 2H), 8.42 (dd, J = 7.8, 1.3 Hz,
1H), 7.96 (d, J = 7.8 Hz, 1H), 7.65 (td, J = 7.7, 1.7 Hz, 1H),
7.30 (d, J = 7.8 Hz, 1H), 7.17 (dd, J = 7.0, 5.3 Hz, 1H), 5.04 (s,
2H), 3.99 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ 167.1,
167.0, 165.1, 154.8, 149.5, 136.6, 135.6, 135.5, 135.3, 132.4,
124.4, 123.4, 122.50, 121.6, 52.7, 43.0.
+
Hz), 42.9. HRMS (ESI-TOF): [M + H]+ calcd for C14H10FN2O2 ,
257.0721; found, 257.0739.
4-Chloro-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione, 2t.
61.5 mg, 75% yield. White solid. Mp: 138.5-140.7 °C. Rf =
0.5 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.52 (d, J =
4.7 Hz, 1H), 7.80 (ddd, J = 5.0, 3.3, 1.6 Hz, 1H), 7.69 – 7.62
(m, 3H), 7.30 (d, J = 7.8 Hz, 1H), 7.20 – 7.15 (m, 1H), 5.01 (s,
2H). 13C{1H} NMR (101 MHz, CDCl3): δ 166.6, 165.6, 154.8,
149.6, 136.7, 135.7, 134.9, 134.2, 131.4, 127.8, 122.5, 121.9,
121.7, 43.0. HRMS (ESI-TOF): [M + H]+ calcd for
5-Nitro-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione, 2n.
26.5 mg, 31% yield. Pale yellow solid. Mp: 157.6-160.1 °C.
Rf = 0.4 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.69 (s,
1H), 8.62 (d, J = 8.1 Hz, 1H), 8.48 (d, J = 4.5 Hz, 1H), 8.09 (d,
J = 8.1 Hz, 1H), 7.67 (t, J = 7.7 Hz, 1H), 7.32 (d, J = 7.8 Hz,
1H), 7.22 – 7.16 (m, 1H), 5.06 (s, 2H). 13C{1H} NMR (101
MHz, CDCl3): δ 166.0, 165.7, 154.2, 151.8, 149.7, 136.8,
136.7, 133.7, 129.2, 124.6, 122.7, 121.8, 118.9, 43.3. HRMS
+
C14H10ClN2O2 , 273.0425; found, 273.0435.
4,6-Dimethyl-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione,
2u. 56.8 mg, 71% yield. White solid. Mp: 132.9-135.3 °C. Rf
= 0.5 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3): δ 8.52 (d, J
= 4.5 Hz, 1H), 7.62 (td, J = 7.7, 1.7 Hz, 1H), 7.50 (s, 1H), 7.27
(d, J = 4.5 Hz, 2H), 7.15 (dd, J = 7.2, 5.1 Hz, 1H), 4.97 (s, 2H),
2.64 (s, 3H), 2.44 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3): δ
+
(ESI-TOF): [M + Na]+ calcd for C14H9N3NaO4 , 306.0485;
found, 306.0473.
5-Phenyl-2-(pyridin-2-ylmethyl)isoindoline-1,3-dione, 2o.
78.4 mg, 83% yield. White solid. Mp: 93.6-95.9 °C. Rf = 0.5
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The Journal of Organic Chemistry
168.8, 168.2, 155.7, 149.5, 144.6, 137.8, 136.8, 136.5, 132.9,
7.66 (dt, J = 7.2, 3.6 Hz, 2H), 7.60 – 7.55 (m, 2H). 13C{1H}
NMR (101 MHz, DMSO): δ 168.7, 132.8, 130.8, 128.4.
1
2
126.3, 122.3, 121.7, 121.4, 42.7, 21.7, 17.4. HRMS (ESI-
+
TOF): [M + H]+ calcd for C16H15N2O2 , 267.1128; found,
267.1147.
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ASSOCIATED CONTENT
Supporting Information
4,6-Dimethoxy-2-(pyridin-2-ylmethyl)isoindoline-1,3-
dione, 2v.6 45.9 mg, 51% yield. White solid. Mp: 135.3-
137.0 °C. Rf = 0.2 (PE/EA = 2/1). 1H NMR (400 MHz, CDCl3):
δ 8.51 (d, J = 4.2 Hz, 1H), 7.61 (td, J = 7.7, 1.5 Hz, 1H), 7.24
(s, 1H), 7.17 – 7.11 (m, 1H), 6.98 (d, J = 1.6 Hz, 1H), 6.64 (d,
J = 1.6 Hz, 1H), 4.96 (s, 2H), 3.96 (s, 3H), 3.90 (s, 3H). 13C{1H}
NMR (101 MHz, CDCl3): δ 167.5, 166.4, 166.3, 158.0, 155.6,
149.3, 136.4, 136.2, 122.1, 121.3, 110.3, 103.5, 100.5, 56.1,
56.0, 42.6.
The Supporting Information is available free of charge on the
ACS Publications website.
1H NMR and 13C NMR spectra for substrates and products
(PDF)
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5-(Pyridin-2-ylmethyl)-4H-thieno[2,3-c]pyrrole-4,6(5H)-
dione, 2w. 24.3 mg, 33% yield. Yellow solid. Mp: 80.3-
81.9 °C. Rf = 0.5 (PE/EA = 2/1). H NMR (400 MHz, CDCl3):
AUTHOR INFORMATION
Corresponding Author
1
δ 8.53 (d, J = 4.3 Hz, 1H), 7.79 (d, J = 4.8 Hz, 1H), 7.64 (td, J
= 7.7, 1.6 Hz, 1H), 7.34 (d, J = 4.8 Hz, 1H), 7.28 (d, J = 7.8 Hz,
1H), 7.17 (dd, J = 7.0, 5.4 Hz, 1H), 4.94 (s, 2H). 13C{1H} NMR
(101 MHz, CDCl3): δ 163.6, 162.4, 155.5, 149.5, 144.7,
140.9, 137.6, 136.7, 122.4, 121.4, 121.3, 121.3, 43.2. HRMS
(ESI-TOF): [M + H]+ calcd for C12H9N2O2S+, 245.0379; found,
245.0394.
*E-mail: yingjun@zstu.edu.cn
*E-mail: xiao-feng.wu@catalysis.de
Notes
The authors declare no competing financial interest.
2-(Quinolin-8-yl)isoindoline-1,3-dione, 2e’.3 16.5 mg, 20%
yield. White solid. Mp: 223.8-225.2 °C. Rf = 0.4 (PE/EA =
ACKNOWLEDGMENT
We acknowledge financial supports from the Zhejiang Natural
Science Fund for Young Scholars (LQ18B020008), Zhejiang
Sci-Tech University (17062078-Y), and National Natural
Science Foundation of China (21772177).
1
5/1). H NMR (400 MHz, CDCl3): δ 8.85 (dd, J = 4.2, 1.6 Hz,
1H), 8.23 (dd, J = 8.3, 1.5 Hz, 1H), 7.98 (ddd, J = 9.4, 6.8, 2.1
Hz, 3H), 7.84 – 7.77 (m, 2H), 7.75 (dd, J = 7.3, 1.3 Hz, 1H),
7.72 – 7.65 (m, 1H), 7.44 (dd, J = 8.3, 4.2 Hz, 1H). 13C{1H}
NMR (101 MHz, CDCl3): δ 167.9, 150.9, 144.3, 136.2, 134.2,
132.4, 130.2, 129.8, 129.6, 129.3, 126.1, 123.8, 121.9.
Transformations of Product 2a. A round bottom flask
charged with a magnetic stir bar was added the
phthalimide 2a (71.4 mg, 0.3 mmol, 1.0 equiv), Zn dust
(149 mg, 2.3 mmol, 7.6 equiv) and acetic acid (3 mL) and
the flask was heated at 120 °C in oil bath for 6 h. After
cooling to ambient temperature, the mixture was diluted
with EtOAc and washed with water. The organic layer was
dried over anhydrous Na2SO4, filtered and concentrated.
The crude mixture was purified by silica gel column
chromatography (PE/EtOAc = 1/1 to 1/2) to obtain the
desired product 3a in 78% yield.7
2-(Pyridin-2-ylmethyl)isoindolin-1-one, 3a. 52.7 mg, 78%
yield. White solid. Mp: 85.9-87.6 °C. Rf = 0.15 (EA). 1H NMR
(400 MHz, CDCl3): δ 8.55 (d, J = 4.8 Hz, 1H), 7.88 (d, J = 7.5
Hz, 1H), 7.64 (td, J = 7.7, 1.7 Hz, 1H), 7.53 (td, J = 7.4, 0.8 Hz,
1H), 7.49 – 7.40 (m, 2H), 7.31 (d, J = 7.8 Hz, 1H), 7.19 (dd, J
= 7.1, 5.2 Hz, 1H), 4.93 (s, 2H), 4.45 (s, 2H). 13C{1H} NMR
(101 MHz, CDCl3): δ 168.4, 156.8, 149.2, 141.3, 136.9,
132.3, 131.3, 127.8, 123.7, 122.7, 122.4, 122.2, 50.1, 48.1.
HRMS (ESI-TOF): [M + H]+ calcd for C14H13N2O+, 225.1022;
found, 225.1027.
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