One-Pot Synthesis of Seven-Membered Heterocyclic Derivatives of Diazepines Involving Copper-Catalyzed Rearrangement Cascade Allyl-Amination

Article abstract of DOI:10.1021/acs.joc.9b02710

A novel and efficient method has been proposed for the synthesis of 1,4-benzodiazepine-5-ones from o-nitrobenzoic N-allylamides by using molybdenyl acetylacetonate and copper(II) trifluoromethanesulfonate as catalysts in the presence of triphenylphosphine. This synthesis process involves nitrene formation, C-H bond insertion, C≠C bond rearrangement, and C-N bond formation cascade reactions via copper- and molybdenum-catalyzed mediation. The method features a wide substrate scope and a moderate to high yield (up to 90%), exhibiting the possibility for practical applications.

Full text of DOI:10.1021/acs.joc.9b02710

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Article
One-Pot Synthesis of Seven-membered Heterocyclic
Derivatives of Diazepines Involving Copper-
Catalyzed Rearrangement Cascade Allyl-Amination
Yuepeng Chen, Xinglei Liu, Wei Shi, Shilong Zheng, Guangdi Wang, and Ling He
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02710 • Publication Date (Web): 17 Mar 2020
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One-Pot Synthesis of Seven-membered Heterocyclic
Derivatives of Diazepines Involving Copper-Catalyzed
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Rearrangement Cascade Allyl-Amination
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Yuepeng Chen,a Xinglei Liu,a Wei Shi,a Shilong Zheng,b Guangdi Wang,b Ling Hea*
a Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan
Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,
West China School of Pharmacy, Sichuan University, Chengdu 610041, China.b RCMI Cancer Research Center and
Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA
Yuepeng Chen:
Xinglei Liu:
Wei Shi:
cyp610327@sina.com
xinleiliu-CHN@outlook.com
1098465897@qq.com
szheng@xula.edu
Shilong Zheng:
Guangdi Wang:
Ling He:
gwang@xula.edu
heling2012@scu.edu.cn
O
O
MoO2(acac)2
Cu(CF3SO3)2
R1
PPh3,Toluene
110°C,12h
R2
R1=H,CH3,OCH3,F,Cl
R2=Methyl,Aryl,aryl methyl,aryl ethyl
R3=H,CH3
R4=H,CH3
R5=H,Allyl
R2
N
N
NO2
R4
R1
R3
R3
N
R5
H
R5
R4
One-pot synthesis of 1,4-benzodiazepine-5-one derivatives
Strategy via nitrene formation, C-H insertion, C-N formation and C=C rearrangement
27 samples, moderate to high yields ( up to 90%)
ABSTRACT: A novel and efficient method has been proposed for the synthesis of
1,4-benzodiazepine-5-ones from o-nitrobenzoic N-allylamides by using molybdenyl
acetylacetonate and copper(II) trifluoromethanesulfonate as catalysts, in the presence of
triphenylphosphine. This synthesis process involves nitrene formation, C-H bond insertion, C=C
bond rearrangement and C-N bond formation cascade reactions via copper and
molybdenum-catalyzed mediation. The method features a wide substrate scope and a moderate to
high yield (up to 90%), exhibiting the possibility for practical applications.
INTRODUCTION
The construction of 1,4-benzodiazepine-5-one derivatives has practical application value in the
development of new drugs.1 Compounds containing benzodiazepine nucleus are of great
significance in the study of pharmacochemistry,2 attracting the attention of many scientists.3 In the
past few decades, these compounds have explicitly exhibited fascinating biological activities, such
as
anti-HIV,5
anti-bacteria,6,7
anti-anxiety,8,9
anti-thrombosis,10
anti-oxidation,11
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anti-hypertension,12 and they are also used in the treatment of ischemic injury,13 muscle relaxant,14
and diabetes insipidus.15 In recent years, more attractive molecules including broad-spectrum
antitumor antibiotics (e.g. anthramycin16,17 and diazepinomicin18), BRD4 inhibitors (e.g.
GSK525762A19), and anticonvulsant agent (e.g. GABAA agonist20) have been discovered (Figure
1).
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Figure 1. Bioactive molecules containing benzodiazepine nucleus
N
N
OH
OMe
H
H
N
N
Me
NH
N
O
NH2
N
O
O
O
anthramycin
GSK525762A
N
N
CH3
CH3
CH3
CH3
N
Cl
O
O
N
N
O
HN
OH
N
H
OH
HO
Br
diazepinomicin
GABAA agonist
Over the past decades, some synthesis of benzodiazepine skeleton have been reported. (Scheme
1, previous work). The first method of constructing seven-membered heterocycles was through
C-C bond formation by photocatalytic decarboxylation of the substrate, and intramolecular C-C
coupling containing carbonyl groups.21 The C-C bond was formed by the electrophilic substitution
of benzene ring by Fischer alkylation or acylation, and the coupling reaction catalyzed by
palladium was carried out under CO atmosphere. The second method was through C-N formation,
such as the nucleophilic substitution reaction of amino p-benzene ring,22 or the intramolecular SN2
nucleophilic substitution reaction of amino group to halogenated alkyl group.23 The C-N bond
could also be constructed by the condensation reaction between amino group and carbonyl
group,24 such as Liu Carter-like-condensation reaction between amine group and carboxylic acid
derivatives,25 and Pictet-Spengler-like reaction26 of phenylalkylamine derivatives and aldehydes.24
For example, Broggini group achieved regioselective formation of seven-membered diazepinone
rings by intramolecular Pd-catalyzed amination of N-allyl-anthranilamides and C-H activation
method.27
Scheme 1 Synthesis of benzodiazepine derivatives
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Previous work
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NO2
NH
Zn/HOAC
N3
CN
NH
Reductive
amination
Microwave
radiation
9
NO2
Aromatic ring
nucleophilic
substitution
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Insertion reaction
Photocatalytic
decarboxylation
cyclization
H
N
NH2
HOOC
N
Formation of C-N bonds
H
N
H
O
N
H
NH2
Cl
Nitrogen
alkylation
H
N
Formation of C-C
Formation of C-N
H
NH
N
Amino and
carbonyl
condensation
O
H
N
NH2
Br
N
Formation of C-C
and C-N bonds
H
F C alkylation
Intramolecular
Aminolysis
Cl
N
H
NH2
O
Intramolecular coupling
catalyzed by palladium
Reaction of Pictet-Spengler
H
H
N
N
NH2
H2N
H
O
Br
CO
R
This work
O
O
R2
MoO2(acac)2
Cu(CF3SO3)2
R1=H,CH3,OCH3,F,Cl
R2=Methyl,Aryl,aryl methyl,aryl ethyl
R3=H,CH3
R4=H,CH3
R5=H,Allyl
R2
N
N
R1
R1
R3
R3
PPh3,Toluene,
110°C,12h
NO2
R4
N
R5
H
R5
R4
Wolfe group synthesized saturated 1,4-benzodiazepines via Pd-catalyzed carboamination reactions
with constructing C-C and C-N bonds simultaneously.28 Grunewald team prepared a series of
benzodiazepinone derivatives which acted as selective inhibitors of EC 2.1.1.28 enzyme from
2,3-dihydroquinolin-4(1H)-one by means of azide insertion.29 Vincenzo Santagada group
developed microwave enhanced solution synthesis of 1,4-benzodiazepin-5-ones from aromatic
primary amines or azides and olefins.30 Doemling group developed diverse 1,4-benzodiazepine
scaffolds by Ugi-four-component reactions.31 As part of our interest in the synthesis of
seven-membered heterocyclic derivatives of diazepines, we herein report the one-pot synthesis of
1,4-benzodiazepine-5-ones with wide substrate scope and moderate to high yields (Scheme 1, this
work).
RESULTS AND DISCUSSION
Initially, we began to investigate the best reaction conditions by using N-(furan-2-
ylmethyl)-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide 1aa, PPh3 and MoO2Cl2(dmf)2 under the
condition of toluene refluxing (Table 1). To our delight, the target compound 4-(furan-2-
ylmethyl)-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one 2a could be
obtained, but the yield was only 20%, and the majority of aniline derivative 3a was produced as
by-product (entry 2). Next, we screened a series of Mo catalysts and found that Mo acetylacetone
may be the most effective catalyst (entry 3). At the same time, the Mo-group-metal catalysts,
tungsten hexacarbonyl and chromium acetylacetone were examined, they could not initiate the
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formation of target product (entry 14-15). Subsequently, we expanded the screening range of the
catalysts including bis(2,4-pentanedionic acid) platinum(II), bis(triphenylphosphine) nickel
chloride, iron acetate, Pd(OAc)2, CuCl2, Ru3(CO)12, Rh(CO)2(C5H7O2) respectively, but could not
deliver the target compound (entry 7-13). To increase the yield, we used two catalysts to promote
the reactions. When MoO2Cl2(dmf)2 and CuCl2 were used together, the yield of the target product
was increased to 45% (entry 16). Fortunately, when we combined MoO2(acac)2 with
Cu(CF3SO3)2, the yield of the target product was increased to 90% (entry 1), and only trace of the
aniline derivative detected. With the optimal catalyst in hand, we investigated the solvent effect on
this reaction and different solvents including dichloromethane, tetrahydrofuran, acetone,
acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide have been compared with refluxing in
the presence of MoO2(acac)2, Cu(CF3SO3)2 and PPh3. The experimental results showed that the
reaction didn’t occur in them (entry 18-22). Therefore, we decided to use MoO2(acac)2 and
Cu(CF3SO3)2 as catalysts, anhydrous toluene as solvent in the atmosphere of N2 at 110 oC, then we
screened reductants, the yield of target product was 90% by using PPh3 (entry 1). Regretfully, its
yields were only 43% and 51% when using S-(-)-BINAP and xantphos, respectively (entry 24,25).
The reaction did not occur by applying trimethylphosphine or no reductant (entry 23,26). In
addition the reaction temperature and time were also investigated, using MoO2(acac)2 and
Cu(CF3SO3)2 as catalysts, anhydrous toluene as solvent and PPh3 as reductant under N2
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o
o
atmosphere. When reaction temperature varied from 30 C to 60 C, no desired product appeared
o
(entry 27-28). The desired compound was produced when the temperature reached 80 C (entry
o
o
29), the yield of the product was over 85% when temperature raised to 110 C or 140 C (entry
29-30). Furthermore, we found that prolonging reaction time could increase the yields, but the
yield was almost same when the other reaction conditions unchanged from 12 h to 16 h (entry
o
31-33). Finally, the reaction was completed well at 110 C for 12 h using substrate 1aa (0.16
mmol), MoO2(acac)2 (10mol%), Cu(CF3SO3)2 (10mol%), PPh3 (2.5 equiv), toluene (2 mL)
respectively.
Based on the optimized conditions, the scope and generality of a series of
1,4-benzodiazepine-5-one derivatives were then evaluated. As shown in Table 2, the reaction
could proceed well to afford corresponding products in moderate to high yields. The structure was
further ambiguously confirmed by single crystal X-ray synthesis of compound 2z (Figure 2).
Table 1. Screening Optimal Conditions a
O
O
O
O
MoO2(acac)2
Cu(CF3SO3)2
O
O
N
N
N
PPh3,Toluene
110°C,12h
NH2
NO2
1aa
N
H
2a
3a
Entry
Variation from the standard conditions
none
2a Yield b 3a Yield b
1
2
90%
20%
-
35%
MoO2Cl2(dmf)2 instead of MoO2(acac)2 and Cu(CF3SO3)2
3
52%
20%
MoO2(acac)2 without Cu(CF3SO3)2
4
5
6
7
Mo(CO)6 instead of MoO2(acac)2 and Cu(CF3SO3)2
CoMoO4 instead of MoO2(acac)2 and Cu(CF3SO3)2
Pt(acac)2 instead of MoO2(acac)2 and Cu(CF3SO3)2
Ni(PPh3)2Cl2 instead of MoO2(acac)2 and Cu(CF3SO3)2
40%
11%
trace
trace
trace
N.R.c
-
-
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Fe(OAc)2 instead of MoO2(acac)2 and Cu(CF3SO3)2
Pd(OAc)2 instead of MoO2(acac)2 and Cu(CF3SO3)2
CuCl2 instead of MoO2(acac)2 and Cu(CF3SO3)2
Cu(CF3SO3)2 without MoO2(acac)2
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
-
-
-
-
-
-
-
-
9
10
11
12
13
14
15
16
Ru3(CO)12 instead of MoO2(acac)2 and Cu(CF3SO3)2
Rh(CO)2(C5H7O2) instead of MoO2(acac)2 and Cu(CF3SO3)2
W( CO)6 instead of MoO2(acac)2 and Cu(CF3SO3)2
Cr(acac)3 instead of MoO2(acac)2 and Cu(CF3SO3)2
MoO2Cl2(dmf)2 ,CuCl2 instead of MoO2(acac)2 and
Cu(CF3SO3)2
10
11
12
13
14
15
16
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22
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60
45%
-
17
18
MoO2Cl2(dmf)2 instead of MoO2(acac)2
66%
N.R.
N.R.
N.R.
N.R.
10%
CH2Cl2 instead of toluene
THF instead of toluene
CH3CN instead of toluene
DMF instead of toluene
-
-
-
-
19
20
21
22
DMSO instead of toluene
(CH3)3P instead of PPh3
S-(-)-BINAP instead of PPh3
Xantphos instead of PPh3
no PPh3
N.R.
N.R.
43%
51%
N.R.
-
-
-
-
-
23
24
25
26
27
30 oC instead of 110 oC
60 oC instead of 110 oC
80 oC instead of 110 oC
140 oC (xylene)instead of 110 oC
4 h instead of 12 h
N.R.
N.R.
5%
-
-
-
-
-
-
-
28
29
30
31
32
33
87%
53%
80%
90%
8 h instead of 12 h
16 h instead of 12 h
aReaction conditions: 1aa (0.16 mmol), MoO2(acac)2 (10mol%), Cu(CF3SO3)2 (10mol%),
PPh3 (2.5 equiv), toluene (2 mL) under N2 at 110 oC for 12 h. bIsolated yield. cNo reaction
Table 2. The formation of diazepines derivatives from the aromatic nitro derivatives a
Procedure A:
O
O
1) SOCl2,reflux,2h
R2
OH
NO2
N
2) R2-NH2 (1.1 equiv)
R1
R1
H
pyridine,DCM
ice-bath to r.t,6-10h
NO2
Procedure B:
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R3
O
Br
(1.5 equiv)
R2
O
R5
N
R2
R4
R1
R3
N
NO2
R4
R1
H
LDA(1.5 equiv),THF
ice-bath to r.t,5h
R5
NO2
9
Procedure C:
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60
MoO2(acac)2 (10%)
Cu(CF3SO3)2 (10%)
O
O
R2
R1=H,CH3,OCH3,F,Cl
R2=Methyl,Aryl,aryl methyl,aryl ethyl
R3=H,CH3
R4=H,CH3
R5=H,Allyl
R2
N
PPh3 (2.5 equiv)
N
R1
R1
R3
R3
Toluene
110°C,12h
NO2
R4
N
R5
H
R5
R4
Cl
H
H
H
N
H
H
N
N
N
N
F
O
O
O
O
O
N
N
N
N
O
N
O
O
O
O
O
2e
52%
2d
2a
2c 83%
81%
90%
2b
60%
H
N
H
N
H
N
Cl
H
N
H
N
S
N
N
S
N
O
S
S
N
N
O
N
O
O
O
2j
63%
2i
68%
2h
64%
2g
59%
2f
65%
H
Cl
H
H
N
H
N
H
N
N
N
N
N
N
N
N
O
O
S
O
O
S
O
S
2o
53%
2n
90%
2l
2m
53%
54%
2k
83%
H
H
N
H
N
N
H
N
H
N
N
N
N
N
N
O
O
O
O
O
F
F
2s
68%
2t
60%
F
2r
50%
2q
66%
2p
83%
H
N
H
H
H
N
N
N
H
N
N
N
O
N
N
O
O
N
O
O
O
O
O
2y
51%
2x
53%
2w
2v
79%
75%
2u
80%
H
N
H
N
N
N
O
O
2z
51%
2a
1 49%
a Reaction conditions: substrate (1 equiv)/ MoO2(acac)2 (10%)/ Cu(CF3SO3)2 (10%)/ PPh3 (2.5
equiv)/ toluene under N2 at 110 oC for 12 h.
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Figure 2. X-ray crystal structure of compound 2z
5
6
7
H
N
8
9
N
O
10
11
12
13
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60
2z
Ellipsoids are shown at the 50% probability level for the ORTEP diagram of the structure.
To comprehend the reaction well, we performed a series of experiments to observe the
special effects of different substrates on the synthesis (Scheme 2). The effect of C-H activation
with rearrangement of the double bond on the reaction was first investigated. Under standard
reaction condition, the ratio of hydrogen to deuterium between the corresponding product obtained
by the reaction and the starting material of the reaction remained unchanged (Scheme 2, reaction
1). Meanwhile, in the presence of methyl on the side chain alkene, the reaction could still obtain a
yield of 80% (reaction 2). The results showed that the carbon-hydro activation of alkene
hydrogen was not necessary. It could also suggest that the double bond migration occurred prior to
the C-N bond formation. To confirm this point, reaction 3 was tested (Scheme 2, reaction 3). The
reaction could not occur and the corresponding cyclization products could not be detected.
Scheme 2 Exploration of reaction mechanism
O
O
O
MoO2(acac)2
Cu(CF3SO3)2
O
N
N
(1)
PPh3,toluene
110°C,12h
H(D)
H(D)
NO2
N
H
1aa'
H:D=3:7
H:D=3:7
O
O
O
MoO2(acac)2
Cu(CF3SO3)2
O
N
N
(2)
PPh3,toluene
110°C,12h
NO2
N
H
1uu
2u
80%
O
O
MoO2(acac)2
Cu(CF3SO3)2
N
(3)
No cyclization product
PPh3,toluene
110°C,12h
NO2
On the basis of our experimental results and the previous mechanism investigations, it is
speculated that MoO2(acac)2 is necessary for the reaction, Cu(CF3SO3)2 can significantly increase
the yield of the reaction. Therefore, a plausible mechanism is suggested that starting from
substrate 1a, MoO2(acac)2 interacts with PPh3 to reduce nitro group of the substrate 1a to the
nitrene intermediate c, and with the participation of Cu(CF3SO3)2 to form N-Cu bond. Next, with
double bond carbon and allyl hydrogen to form a cyclohexanic intermediate d. Then the allyl
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hydrogen was removed, the double bond was rearranged at the same time and to form N-H bond
and to give the intermediate e. Finally get the target compound 2a and release catalyst
Cu(CF3SO3)2. In short, we postulated the mechanism as shown in Scheme 3. The novel diazepines
synthesis possibly occurred via reduction of nitro group, followed by the removal of
allyl-hydrogen in the presence of divalent copper Cu (II), rearrangement of double bond.
Scheme 3 Postulated mechanism
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Cu(CF3SO3)2
O
O
O
N
O
N
N
H
N
Ph3PO
MoO(acac)2
c
(F3CSO3)2Cu
H
H
H
Ph3P
d
O
O
O
O
N
H
N
MoO2(acac)2
H
N
H
N
(F3CSO3)2Cu
O
H
b
e
O
MoO(acac)2
Ph3PO
O
N
O
N
O
Cu(O3SCF3)2
Ph3P
N
H
NO2
MoO2(acac)2
2a
1a
CONCLUSIONS
In summary, we have successfully developed an efficient one-pot strategy for the construction of
1,4-benzodiazepine-5-ones from the derivatives of N-(3-methylbut-2-en-1-yl)-2- nitrobenzamide
by using MoO2(acac)2 and Cu(CF3SO3)2 as co-catalyst. The tandem annulation procedure involves
the reduction of nitro group, the formation of nitrene, C − H activation and the formation of
cyclohexanic intermediate, and followed by the removal of allyl-hydrogen in the presence of
divalent copper Cu (II), rearrangement of the double bond, a subsequent intramolecular
cyclization process. This catalytic system exhibits good functional group tolerance. We have
preliminarily explored the antineoplastic activity of these compounds, which could be important
intermediates in the synthesis of some biologically active seven-membered nitrogen heterocycles
compounds, and further research is underway. We expect that this approach could be widely used
in the formation of various heterocyclic frameworks in our future research.
EXPERIMENTAL SECTION
General Methods. NMR experiments were accomplished on a 400 MHz or 600 MHz
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spectrometer. Column chromatography was performed on silica gel H. ESI mass spectra analyses
were completed on a Thermo Fisher Scientific LTQ FT Ultra mass spectrometer. o-Nitrobenzoic
acid including its substituted derivatives and all solvents were obtained from commercial sources
and were used as received or after drying and re-distillation. All o-nitrobenzoic N-allylamides
were prepared according to the literature. Chromatographic separation was performed on a silica
gel H column using petroleum ether (PE)/ethyl acetate (EA) as a mobile phase. All reactions were
carried out under a nitrogen atmosphere.
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General procedure A: Preparation of N-(furan-2-ylmethyl)-2-nitrobenzamide32 (1a). The
preparation strategies of the other derivatives were consistent with its preparation strategy.
o-Nitrobenzoic acid (500 mg, 2.99 mmol) was placed in a 250 mL clean anhydrous round-bottom
flask under nitrogen atmosphere. Sulfoxide dichloride (4 mL) was added into the flask, and the
o
mixture was stirred at 80 C for 2 hours. After completing the reaction, the redundant sulfoxide
dichloride was removed under reduced pressure to obtain o-nitrobenzoyl chloride.
Furamethylamine (0.32 mL, 3.3 mmol) was placed in another 250 mL dried round-bottom flask
with stirring under anhydrous condition and nitrogen atmosphere. Anhydrous CH2Cl2 (20 mL) and
pyridine (3 mL) were injected into the flask by a syringe. Then the prepared o-nitrobenzoyl
chloride was added under the ice bath. After completing the above operation, the flask was placed
at room temperature with stirring for 10 hours. TLC plate monitored the end of the reaction,
quenched by adding saturated sodium bicarbonate solution (50 mL) and extracted by using ethyl
acetate (30 mL × 2), washed with saturated sodium chloride solution (50 mL), dried over Na2SO4
and concentrated under reduced pressure. Purification was done by column chromatography on
silica gel H with petroleum ether/ethyl acetate (3:1) as eluent to give the pure white solid (664
mg).
N-(Furan-2-ylmethyl)-2-nitrobenzamide (1a, 1u, 1w). Prepared from o-nitrobenzoic acid (500
mg, 2.99 mmol) with furfurylamine (0.32 mL, 3.3 mmol) purifued following general procedure A;
afforded 664 mg (90% yield) of the title compound as a off-white solid: Rf = 0.32 (2:1 PE/EA), mp
108-109 oC; 1H NMR (400 MHz, Chloroform-d) δ 8.06 (dd, J = 8.0, 1.4 Hz, 1H), 7.67 (td, J = 7.5, 1.3
Hz, 1H), 7.58 (td, J = 8.0, 1.6 Hz, 1H), 7.52 (dd, J = 7.5, 1.6 Hz, 1H), 7.38 (t, J = 1.2 Hz, 1H), 6.35 (d,
J = 1.2 Hz, 2H), 6.21 (s, 1H), 4.65 (d, J = 5.5 Hz, 2H); Literature data33: White solid; mp 108–110
°С; 1H NMR (300 MHz, CDCl3) δ 4.56 (2H, d, J = 5.7 Hz), 6.29 (1H, dd, J = 3.3 Hz, J = 0.9 Hz),
6.32 (1H, dd, J = 1.8 Hz, J = 3.3 Hz), 6.42 (1H, m, J = 5.7 Hz), 7.34 (1H, dd, J = 1.8 Hz, J = 0.9
Hz), 7.44-7.47 (1H, m), 7.50-7.56 (1H, m), 7.59-7.65 (1H, m), 7.98-8.01 (1H, m); 13C｛1H｝
NMR (75 MHz, CDCl3) δ 37.1, 107.9, 110.5, 124.5, 128.7, 130.5, 132.4, 133.7, 142.3, 146.1,
150.3, 166.2.
3-Chloro-N-(furan-2-ylmethyl)-2-nitrobenzamide (1b). Prepared from 3-chloro-2-nitrobenzoic
acid (500 mg, 2.49 mmol) with furfurylamine (0.27 mL, 2.81 mmol) purifued following general
procedure A; afforded 610 mg (87% yield) of the title compound as a white solid: Rf = 0.5 (2:1
o
1
PE/EA), mp 121-122 C; H NMR (600 MHz, Chloroform-d) δ 7.60 (d, J = 7.9 Hz, 1H), 7.52 (d, J =
7.5 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.37 (s, 1H), 6.44 (s, 1H), 6.34 (d, J = 2.9 Hz, 1H), 6.30 (d, J =
2.9 Hz, 1H), 4.56 (d, J = 5.4 Hz, 2H).
N-(Furan-2-ylmethyl)-5-methyl-2-nitrobenzamide (1c). Prepared from 5-methyl-2-nitrobenzoic
acid (500 mg, 2.76 mmol) with furfurylamine (0.3 mL, 3.12 mmol) purifued following general
procedure A; afforded 665 mg (93% yield) of the title compound as a off-white solid: Rf = 0.3 (2:1
PE/EA); mp 135-137 oC; 1H NMR (600 MHz, Chloroform-d) δ 7.97 (d, J = 8.3 Hz, 1H), 7.38 (s, 1H),
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7.34 (d, J = 8.3 Hz, 1H), 7.29 (s, 1H), 6.35 (s, 2H), 6.18 (s, 1H), 4.63 (d, J = 5.4 Hz, 2H), 2.44 (s, 3H);
13C｛1H｝ NMR (150 MHz, Chloroform-d) δ 166.6, 150.4, 145.4, 143.9, 142.4, 132.7, 130.9, 129.3,
124.7, 110.6, 108.0, 37.2, 21.4; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C13H13O4N2, 261.0870;
found, 261.0868.
N-(Furan-2-ylmethyl)-5-methoxy-2-nitrobenzamide (1d). Prepared from 5-methoxy-2-
nitrobenzoic acid (500 mg, 2.54 mmol) with furfurylamine (0.28 mL, 2.87 mmol) purifued
following general procedure A; afforded 668 mg (95% yield) of the title compound as a brown
solid: Rf = 0.4 (2:1 PE/EA), mp 131-133 oC; 1H NMR (600 MHz, Chloroform-d) δ 8.11 (d, J = 9.1 Hz,
1H), 7.37 (s, 1H), 6.97 (dd, J = 9.1, 1.8 Hz, 1H), 6.93 (d, J = 1.8 Hz, 1H), 6.35 (s, 2H), 6.15 (s, 1H),
4.64 (d, J = 5.4 Hz, 2H), 3.90 (s, 3H); 13C｛1H｝ NMR (150 MHz, Chloroform-d) δ 166.4, 163.7, 150.3,
142.3, 138.7, 135.1, 127.1, 115.0, 113.9, 110.6, 108.0, 56.2, 37.2.
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4-Fluoro-N-(furan-2-ylmethyl)-2-nitrobenzamide (1e). Prepared from 4-fluoro-2-nitrobenzoic
acid (500 mg, 2.70 mmol) with furfurylamine (0.38 mL, 3.05 mmol) purifued following general
procedure A; afforded 509 mg (71% yield) of the title compound as a white solid: Rf = 0.38 (2:1
PE/EA), mp 115-117 oC; 1H NMR (600 MHz, DMSO-d6) δ 9.20 (t, J = 5.7 Hz, 1H), 8.02 (d, J = 8.4 Hz,
1H), 7.69 (d, J = 5.7 Hz, 2H), 7.61 (s, 1H), 6.43 (s, 1H), 6.34 (s, 1H), 4.43 (d, J = 5.5 Hz, 2H); 13C｛1H｝
NMR (150 MHz, DMSO-d6) δ 164.8, 162.1 (d, J = 249.0 Hz), 151.9, 148.7 (d, J = 9.0 Hz), 142.7,
131.7 (d, J = 9.0 Hz), 128.8 (d, J = 3.0 Hz), 120.8 (d, J = 22.5 Hz), 112.5 (d, J = 27.0 Hz), 111.0, 107.5,
36.6; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C12H10O4N2F, 265.0619 ; found, 265.0626.
2-Nitro-N-(thiophen-2-ylmethyl)benzamide (1f). Prepared from 2-nitrobenzoic acid (500 mg,
2.99 mmol) with thiophen-2-ylmethanamine (0.4 mL, 3.4 mmol) purifued following general
procedure A; afforded 670 mg (86% yield) of the title compound as a off-white solid: Rf = 0.3 (2:1
PE/EA), mp 117-119 oC; 1H NMR (400 MHz, Chloroform-d) δ 8.05 (d, J = 8.0 Hz, 1H), 7.66 (t, J
= 7.4 Hz, 1H), 7.57 (t, J = 7.3 Hz, 1H), 7.52 (d, J = 7.4 Hz, 1H), 7.25 (d, J = 4.3 Hz, 1H), 7.07 (d,
J = 3.0 Hz, 1H), 6.98 (dd, J = 4.8, 3.6 Hz, 1H), 6.24 (s, 1H), 4.81 (d, J = 5.6 Hz, 2H).
3-Chloro-2-nitro-N-(thiophen-2-ylmethyl)benzamide (1g). Prepared from 3-chloro-2-
nitrobenzoic acid (500 mg, 2.49 mmol) with thiophen-2-ylmethanamine (0.33 mL, 2.81 mmol)
purifued following general procedure A; afforded 672 mg (91% yield) of the title compound as a
off-white solid: Rf = 0.28 (2:1 PE/EA), mp 164-165 oC; 1H NMR (400 MHz, Chloroform-d) δ 7.59 (dd,
J = 7.7, 1.0 Hz, 1H), 7.44-7.51 (m, 2H), 7.25 (d, J = 1.7 Hz, 1H), 7.02 (d, J = 1.7 Hz, 1H), 6.96 (t, J =
4.2 Hz, 1H), 6.38 (s, 1H), 4.73 (d, J = 5.6 Hz, 2H).
5-Methyl-2-nitro-N-(thiophen-2-ylmethyl)benzamide (1h). Prepared from 5-methyl-2-
nitrobenzoic acid (500 mg, 2.76 mmol) with thiophen-2-ylmethanamine (0.37 mL, 3.12 mmol)
purifued following general procedure A; afforded 668 mg (88% yield) of the title compound as a
brown solid: Rf = 0.32 (2:1 PE/EA), mp 138-139 oC; 1H NMR (400 MHz, Chloroform-d) δ 7.96 (d, J
= 8.4 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 7.27 (d, J =1.1 Hz, 1H), 7.25 (dd, J = 5.1, 1.2 Hz, 1H), 7.06 (d,
J = 2.9 Hz, 1H), 6.97 (dd, J = 5.1, 3.5 Hz, 1H), 6.23 (s, 1H), 4.79 (d, J = 5.6 Hz, 2H), 2.44 (s, 3H); 13C
｛1H｝ NMR (150 MHz, Chloroform-d) δ 166.4, 145.4, 143.8, 139.8, 132.6, 130.8, 129.2, 127.0, 126.5,
125.5, 124.6, 38.8, 21.4; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C13H13O3N2S, 277.0641; found,
277.0639.
3-Methyl-2-nitro-N-(thiophen-2-ylmethyl)benzamide (1i). Prepared from 3-methyl-2-
nitrobenzoic acid (500 mg, 2.76 mmol) with thiophen-2-ylmethanamine (0.37 mL, 3.12 mmol)
purifued following general procedure A; afforded 679 mg (89% yield) of the title compound as a
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white solid: Rf = 0.3 (2:1 PE/EA), mp 135-136 oC; 1H NMR (400 MHz, Chloroform-d) δ 7.40 (s, 3H),
7.24 (d, J = 4.7 Hz, 1H), 7.03 (d, J = 3.0 Hz, 1H), 6.96 (dd, J = 4.7, 3.6 Hz, 1H), 6.41 (s, 1H), 4.73 (d, J
= 5.6 Hz, 2H), 2.37 (s, 3H).
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2-Nitro-N-(2-(pyridin-2-yl)ethyl)benzamide (1j). Prepared from 2-nitrobenzoic acid (500 mg,
2.99 mmol) with 2-(pyridin-2-yl)ethan-1-amine (0.42 mL, 3.4 mmol) purifued following general
procedure A; afforded 720 mg (89% yield) of the title compound as a yellow solid: Rf = 0.56 (EA),
mp 102-103 oC; 1H NMR (400 MHz, Chloroform-d) δ 8.43 (dd, J = 4.5, 0.4 Hz, 1H), 8.00 (dd, J =
8.1, 0.8 Hz, 1H), 7.64 (td, J = 7.6, 1.6 Hz, 2H), 7.54 (td, J = 8.0, 1.4 Hz, 1H), 7.49 (dd, J = 7.5, 1.4
Hz, 1H), 7.27-7.24 (m, 1H), 7.22 (s, 1H), 7.17-7.12 (m, 1H), 3.87 (q, J = 6.0 Hz, 2H), 3.12 (t, J =
6.2 Hz, 2H).
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2-Nitro-N-(2-(thiophen-2-yl)ethyl)benzamide (1k). Prepared from 2-nitrobenzoic acid (500 mg,
2.99 mmol) with 2-(thiophen-2-yl)ethan-1-amine (0.44 mL, 3.4 mmol) purifued following general
procedure A; afforded 740 mg (90% yield) of the title compound as a yellow waxy solid: Rf = 0.3
(2:1 PE/EA); mp 88-90 oC; 1H NMR (600 MHz, Chloroform-d) δ 8.04 (d, J = 8.0 Hz, 1H), 7.64 (t,
J = 7.4 Hz, 1H), 7.56 (t, J = 7.7 Hz, 1H), 7.45 (d, J = 7.4 Hz, 1H), 7.16 (d, J = 4.8 Hz, 1H), 6.94 (d,
J = 4.5 Hz, 1H), 6.91 (s, 1H), 5.99 (s, 1H), 3.74 (q, J = 6.2 Hz, 2H), 3.19 (t, J = 6.4 Hz, 2H).
2-Chloro-2-nitro-N-(2-(thiophen-2-yl)ethyl)benzamide (1l). Prepared from 3-chloro-2-
nitrobenzoic acid (500 mg, 2.49 mmol) with 2-(thiophen-2-yl)ethan-1-amine (0.36 mL, 2.81 mmol)
purifued following general procedure A; afforded 698 mg (90% yield) of the title compound as a
yellow solid: Rf = 0.3 (2:1 PE/EA), mp 134-136 oC; 1H NMR (600 MHz, Chloroform-d) δ 7.59 (d, J =
7.8 Hz, 1H), 7.48-7.43 (m, 2H), 7.18 (d, J = 5.0 Hz, 1H), 6.97 (t, J = 4.1 Hz, 1H), 6.89 (d, J = 2.4 Hz,
1H), 6.18 (s, 1H), 3.67 (q, J = 6.3 Hz, 2H), 3.13 (t, J = 6.5 Hz, 2H).
5-Methyl-2-nitro-N-(2-(thiophen-2-yl)ethyl)benzamide (1m). Prepared from 5-methyl-2-
nitrobenzoic acid (500 mg, 2.76 mmol) with 2-(thiophen-2-yl)ethan-1-amine (0.4 mL, 3.12 mmol)
purifued following general procedure A; afforded 705 mg (88% yield) of the title compound as a
o
1
off-white solid: Rf = 0.33 (2:1 PE/EA); mp 100-102 C; H NMR (600 MHz, Chloroform-d) δ 7.96
(d, J = 8.3 Hz, 1H), 7.32 (d, J = 8.3 Hz, 1H), 7.22 (s, 1H), 7.16 (d, J = 4.8 Hz, 1H), 6.95 (t, J = 4.8 Hz,
1H), 6.91 (s, 1H), 5.99 (s, 1H), 3.73 (q, J = 6.4 Hz, 2H), 3.18 (t, J = 6.4 Hz, 2H), 2.43 (s, 3H); 13C｛1H｝
NMR (150 MHz, Chloroform-d) δ 166.9, 145.3, 143.8, 141.0, 132.9, 130.7, 129.1, 127.1, 125.6, 124.6,
123.9, 41.3, 29.5, 21.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C14H15O3N2S, 291.0798; found,
291.0794.
N-Benzyl-2-nitrobenzamide (1n). Prepared from 2-nitrobenzoic acid (500 mg, 2.99 mmol) with
phenylmethanamine (0.37 mL, 3.4 mmol) purifued following general procedure A; afforded 637
mg (83% yield) of the title compound as a off-white solid: Rf = 0.38 (2:1 PE/EA), mp 123-124 oC; 1H
NMR (600 MHz, Chloroform-d) δ 8.04 (d, J = 8.1 Hz, 1H), 7.65 (td, J = 7.8, 0.4 Hz, 1H), 7.56 (td, J =
7.5,0.7 Hz, 1H), 7.51 (dd, J = 7.5, 0.6 Hz,1H), 7.39–7.34 (m, 4H), 7.31-7.29 (m, 1H), 6.20 (s, 1H), 4.62
1
(d, J = 5.6 Hz, 2H). Literature data34: Light brown solid; mp 121-122 °C; H NMR (300 MHz,
CDCl3) δ 9.21 (t, J = 5.7 Hz, 1H), 8.04 (dd, J = 7.9, 1.0 Hz, 1H), 7.80 (td, J = 7.4, 1.1 Hz, 1H),
7.72-7.64 (m, 2H), 7.36 (m, 4H), 7.27 (m, 1H), 4.46 (d, J = 6.0 Hz, 2H).
N-Benzyl-3-methyl-2-nitrobenzamide (1o, 1a1). Prepared from 3-methyl-2-nitrobenzoic acid (500
mg, 2.76 mmol) with phenylmethanamine (0.34 mL, 3.12 mmol) purifued following general
procedure A; afforded 680 mg (91% yield) of the title compound as a off-white solid: Rf = 0.3 (3:1
o
1
PE/EA), mp 137-138 C; H NMR (400 MHz, Chloroform-d) δ 7.42–7.27 (m, 8H), 6.31 (s, 1H), 4.57
(d, J = 5.7 Hz, 2H), 2.38 (s, 3H).
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N-(2,6-Dimethylbenzyl)-3-methyl-2-nitrobenzamide (1p,1v). Prepared from 3-methyl-2-
nitrobenzoic acid (500 mg, 2.76 mmol) with (2,6-dimethylphenyl)methanamine (0.43 mL, 3.12
mmol) purifued following general procedure A; afforded 734 mg (89% yield) of the title
compound as a white solid: Rf = 0.3 (3:1 PE/EA), mp 153-154 oC; 1H NMR (400 MHz, Chloroform-d)
δ 7.40–7.33 (m, 3H), 7.16-7.12 (m, 1H), 7.07 (d, J = 7.4 Hz, 2H), 5.78 (s, 1H), 4.62 (d, J = 4.6 Hz, 2H),
2.41 (s, 6H), 2.37 (s, 3H); 13C｛1H｝ NMR (150 MHz, Chloroform-d) δ 165.1, 149.2, 137.7, 133.5,
133.1, 131.0, 130.4, 129.9, 128.4, 128.0, 125.8, 38.8, 19.6, 17.6; HRMS (ESI-TOF) m/z: [M + H]+
calcd for C17H19O3N2, 299.1390; found, 299.1394.
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N,3-Dimethyl-2-nitrobenzamide (1q). Prepared from 3-methyl-2-nitrobenzoic acid (542 mg, 2.99
mmol) with iodomethane (0.49 mL, 3.4 mmol) purifued following general procedure A; afforded
478 mg (82% yield) of the title compound as a yellow solid: Rf = 0.12 (3:1 PE/EA), mp 133-135
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C; H NMR (400 MHz, Chloroform-d) δ 7.43-7.36 (m, 3H), 6.18 (s, 1H), 2.93 (d, J = 4.8 Hz, 3H),
2.36 (s, 3H).
N-(4-Fluorophenethyl)-2-nitrobenzamide (1r). Prepared from 2-nitrobenzoic acid (500 mg, 2.99
mmol) with 2-(4-fluorophenyl)ethan-1-amine (0.48 mL, 3.4 mmol) purifued following general
procedure A; afforded 795 mg (92% yield) of the title compound as a off-white solid: Rf = 0.33 (2:1
PE/EA), mp 103-104 oC; 1H NMR (400 MHz, Chloroform-d) δ 8.04 (dd, J = 8.0, 1.2 Hz, 1H), 7.64 (td,
J = 7.5, 1.2 Hz, 1H), 7.55 (td, J = 8.0, 1.5 Hz, 1H), 7.41 (dd, J = 7.4, 1.5 Hz, 1H), 7.24–7.20 (m, 2H),
7.02–6.97 (m, 2H), 5.88 (s, 1H), 3.70 (q, J = 6.9 Hz, 2H), 2.94 (t, J = 6.9 Hz, 2H).
N-(4-Fluorophenethyl)-5-methyl-2-nitrobenzamide (1s). Prepared from 5-methyl-2-nitrobenzoic
acid (500 mg, 2.76 mmol) with 2-(4-fluorophenyl)ethan-1-amine (0.44 mL, 3.12 mmol) purifued
following general procedure A; afforded 778 mg (93% yield) of the title compound as a brown
o
1
solid: Rf = 0.35 (3:1 PE/EA), mp 125-127 C; H NMR (400 MHz, Chloroform-d) δ 8.69 (t, J = 4.4
Hz, 1H), 7.94 (d, J = 8.3 Hz, 1H), 7.47 (d, J = 8.3 Hz, 1H), 7.34–7.26 (m, 3H), 7.13 (t, J = 8.8 Hz, 2H),
3.43 (q, J = 6.8 Hz, 2H), 2.82 (t, J = 7.2 Hz, 2H), 2.41 (s, 3H); 13C｛1H｝ NMR (150 MHz, DMSO-d6)
δ 166.0, 161.3 (d, J = 241.5 Hz), 144.9, 135.8 (d, J = 3 Hz), 133.3, 131.0, 130.9 (d, J = 7.5 Hz), 130.3,
129.7, 124.5, 115.4 (d, J = 21.0 Hz), 41.0, 34.2, 21.1.
N-(4-Fluorophenethyl)-3-methyl-2-nitrobenzamide (1t). Prepared from 3-methyl-2-nitrobenzoic
acid (542 mg, 2.99 mmol) with 2-(4-fluorophenyl)ethan-1-amine (0.48 mL, 3.4 mmol) purifued
following general procedure A; afforded 802 mg (89% yield) of the title compound as a off-white
o
1
solid: Rf = 0.35 (3:1 PE/EA), mp 105-106 C; H NMR (400 MHz, Chloroform-d) δ 8.82 (t, J = 5.3
Hz, 1H), 7.56 (d, J = 5.2 Hz, 2H), 7.48–7.41 (m, 1H), 7.28 (dd, J = 8.3, 5.8 Hz, 2H), 7.12 (t, J = 8.8 Hz,
2H), 3.41 (q, J = 6.9 Hz, 2H), 2.80 (t, J = 7.1 Hz, 2H), 2.29 (s, 3H); 13C｛1H｝ NMR (150 MHz,
DMSO-d6) δ 164.6, 161.1 (d, J = 240.1 Hz), 149.2, 135.6 (d, J = 2.1 Hz), 133.7, 130.7 (d, J = 4.2Hz),
130.6, 130.4, 129.9, 126.3, 115.2 (d, J = 20.9 Hz), 40.9, 34.0, 17.0.
N-(4-Methoxyphenyl)-2-nitrobenzamide (1x). Prepared from 2-nitrobenzoic acid (500 mg, 2.99
mmol) with 4-methoxyaniline (0.42 mL, 3.4 mmol) purifued following general procedure A;
Afforded 787 mg (97% yield) of the title compound as a off-white solid: Rf = 0.46 (2:1 PE/EA), mp
169-170 oC; 1H NMR (400 MHz, Chloroform-d) δ 10.54 (s, 1H), 8.13 (d, J = 8.1 Hz, 1H), 7.86 (t, J =
7.5 Hz, 1H), 7.78–7.72 (m, 2H), 7.59 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.4 Hz, 2H), 3.75 (s, 3H); 13C
｛1H｝NMR (100 MHz, Chloroform-d) δ 163.8, 155.9, 146.8, 134.2, 133.0, 132.2, 131.1, 129.5, 124.4,
121.4, 114.1, 55.4. Literature data35: yellow needles; mp 168-169 °C.
2-Nitro-N-(m-tolyl)benzamide (1y). Prepared from 2-nitrobenzoic acid (500 mg, 2.99 mmol) with
m-toluidine (0.37 mL, 3.4 mmol) purifued following general procedure A; afforded 652 mg (85%
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yield) of the title compound as a brown solid: Rf = 0.16 (3:1 PE/EA); mp 141-143 oC; 1H NMR (400
MHz, Chloroform-d) δ 8.07 (d, J = 8.1 Hz, 1H), 7.72-7.58 (m, 3H), 7.44 (s, 1H), 7.32 (d, J = 7.9 Hz,
1H), 7.23 (d, J = 7.8 Hz, 1H), 6.99 (m, 1H), 6.63–6.50 (m, 1H), 2.35 (s, 3H); 13C｛1H｝ NMR (100
MHz, Chloroform-d) δ 164.5, 139.0, 137.2, 133.8, 132.8, 130.5, 128.8, 128.5, 125.9, 124.5, 121.1,
119.7, 117.5, 21.4. Literature data36: mp 145-147 °C.
2-Nitro-N-phenylbenzamide (1z). Prepared from 2-nitrobenzoic acid (200 mg, 1.2 mmol) with
aniline (0.13 mL, 1.35 mmol) purifued following general procedure A; afforded 236 mg (81%
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yield) of the title compound as a brown solid: Rf = 0.52 (1:1 PE/EA), mp 154-156 C; H NMR
(400 MHz, Chloroform-d) δ 8.10 (d, J = 8.0 Hz, 1H), 7.73–7.56 (m, 6H), 7.37 (t, J = 7.7 Hz, 2H),
7.19 (t, J = 7.3 Hz, 1H).
General procedure B: Synthesis of N-(furan-2-ylmethyl)-N-(3-methylbut-2-en-1-yl)-2-
nitrobenzamide18 (1aa). N-(furan-2-ylmethyl)-2-nitrobenzamide (246 mg, 1 mmol) (1a) was
placed in a 100 mL clean anhydrous round-bottom flask under nitrogen atmosphere, anhydrous
THF (15 mL) was injected by a 20 mL syringe. Then the flask was placed in an ice bath, and LDA
(ca. 2.0 M, 0.75 mL, 1.5 mmol) was added with stirring for 15 minutes. 3,3-dimethylallyl bromide
(220 mg, 1.5 mmol) was slowly dripped into the flask by a 1 mL syringe. After 3 hours, the
reaction was monitored by TLC plate, quenched by adding saturated ammonium chloride solution
(40 mL), extracted with ethyl acetate(25 mL × 2), washed with saturated sodium chloride solution
(20 mL × 2), dried over Na2SO4 and concentrated under reduced pressure. Purification was done
by column chromatography on silica gel H with petroleum ether/ethyl acetate (4:1) as eluent to
give the light yellow oily liquid (266.9 mg). The synthesis process of these compounds was the
same method, the polarity of the products is also similar, all belonging to oily substances.
1
Compound 1pp and 1zz were identified by H/13C NMR and HMRS. The reaction solutions of the
rest of the compounds were separated by rapid chromatographic column and went directly into the
general procedure C.
N-(2,6-Dimethylbenzyl)-3-methyl-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (1pp). Prepared
from N-(2,6-dimethylbenzyl)-3-methyl-2-nitrobenzamide (150 mg, 0.503 mmol) (1p) and
purifued following general procedure B; afforded 116 mg (63% yield) of the title compound as a
yellow oil: Rf = 0.4 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.45–7.37 (m, 1H), 7.33 (d,
J = 7.5 Hz, 1H),7.22 (d, J = 7.4 Hz, 1H), 7.14–7.08 (m, 1H), 7.06–7.00 (m, 2H), 5.10 (t, J = 7.5 Hz,
1H), 4.89 (s, 2H), 3.56 (d, J = 6.0 Hz, 2H), 2.46 (s, 3H), 2.36 (s, 6H), 1.60 (s, 3H), 0.96 (s, 3H); 13C
｛1H｝ NMR (100 MHz, Chloroform-d) δ 167.4, 148.0, 138.5, 135.8, 132.4, 132.3, 132.2, 131.8,
131.0, 128.5, 127.8, 125.3, 120.3, 45.3, 42.5, 25.7, 20.0, 19.0, 17.3; HRMS (ESI-TOF) m/z: [M +
Na]+ calcd for C22H26O3N2Na, 389.1836; found, 389.1839.
N-(3-Methylbut-2-en-1-yl)-2-nitro-N-phenylbenzamide (1zz). Prepared from 2-nitro-N-
phenylbenzamide (123 mg, 0.52 mmol) (1z) and purifued following general procedure B; afforded
112.8 mg (70% yield) of the title compound as a yellow waxy solid: Rf = 0.4 (2:1 PE/EA), 62-64
oC; 1H NMR (400 MHz, Chloroform-d) δ 7.90 (d, J = 8.2 Hz, 1H), 7.45 (t, J = 7.5 Hz, 1H), 7.31 (t, J =
7.8 Hz, 2H), 7.19–6.98 (m, 5H), 5.41 (t, J = 7.0 Hz, 1H), 4.54 (d, J = 7.1 Hz, 2H), 1.71 (s, 3H), 1.51 (s,
3H); 13C｛1H｝ NMR (100 MHz, Chloroform-d) δ 166.6, 145.7, 141.5, 136.9, 133.5, 133.4, 129.4,
129.3, 129.1, 128.2, 127.7, 124.2, 118.6, 47.2, 25.7, 17.8; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C18H19O3N2, 311.1390; found, 311.1391.
General procedure C. 4-(Furan-2-ylmethyl)-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo
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[e][1,4]diazepin-5-one 2a was used as the model product for this reaction. The preparation
strategies of the other diazepines were consistent with its preparation strategy.
N-(furan-2-ylmethyl)-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide 1aa (30 mg, 0.096 mmol) was
placed in a 15 mL test tube with agitator, added with triphenylphosphine (63 mg, 0.24 mmol),
molybdenum-acetoacetate (3.1 mg, 0.0096 mmol), and copper(II) trifluoromethane-sulfonate (3.5
mg, 0.0096 mmol) successively. After that, dried toluene (3 mL) was added into the test tube.
Then the test tube was placed in an oil bath at 110 oC for 12 h. The whole operation process was
carried out without water and oxygen under N2 atmosphere rigidly. TLC plate was used for
monitoring the end of the reaction. The mixture was diluted with ethyl acetate (10 mL) and
washed with saturated sodium chloride solution (15 mL × 2), dried over Na2SO4 and concentrated
under reduced pressure. Purification was done by column chromatography on silica gel H with
petroleum ether/ethyl acetate (4 : 1, v/v) as eluent to give the 2a of white solid (24.4 mg).
4-(Furan-2-ylmethyl)-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one
(2a). Prepared from N-(furan-2-ylmethyl)-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (30 mg,
0.096 mmol) and purified following the procedure C; afforded 24.4 mg (90% yield) of the product
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as a white solid: Rf = 0.45 (2:1 PE/EA), mp 120-122 C; H NMR (400 MHz, Chloroform-d) δ
7.80 (d, J = 7.7 Hz, 1H), 7.37 (s, 1H), 7.26 (t, J = 7.6 Hz, 2H), 6.96 (t, J = 7.6 Hz, 1H), 6.84 (d, J
= 7.7 Hz, 1H), 6.34 (s, 1H), 5.02 (s, 2H), 4.96 (d, J = 15.5 Hz, 2H), 4.53 (d, J = 15.4 Hz, 1H), 4.03
(dd, J = 8.8, 3.1 Hz, 1H), 3.54 (dd, J = 15.2, 8.8 Hz, 1H), 3.41 (dd, J = 15.2, 3.1 Hz, 1H), 1.73 (s,
3H); 13C｛1H｝ NMR (100 MHz, Chloroform-d) δ 169.6, 150.8, 145.4, 144.4, 142.4, 132.4, 132.1,
122.5, 119.6, 119.2, 113.0, 110.6, 109.0, 65.3, 48.6, 43.8, 19.4; HRMS (ESI-TOF) m/z: [M + H]+
calcd for C17H19N2O2, 283.1441; found, 283.1440. Larger scale synthesis: Prepared from
N-(furan-2-ylmethyl)-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (387 mg, 1.23 mmol) and
purified following the procedure C; afforded 208.4 mg (60% yield) of 2a.
9-Chloro-4-(furan-2-ylmethyl)-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-
5-one
(2b).
Prepared
from
3-chloro-N-(furan-2-ylmethyl)-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (36 mg, 0.103 mmol)
and purified following the procedure C; afforded 19.6 mg (60% yield) of the product as a light
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yellow oil: Rf = 0.42 (2:1 PE/EA); H NMR (400 MHz, Chloroform-d) δ 7.73 (dd, J = 7.9, 1.5 Hz,
1H), 7.46–7.35 (m, 2H), 6.77 (t, J = 7.8 Hz, 1H), 6.36 (s, 2H), 5.13 (s, 1H), 5.12 (d, J = 15.3 Hz, 1H),
4.96 (s, 1H), 4.59 (s, 1H), 4.43 (d, J = 15.3 Hz, 1H), 4.00 (dd, J = 8.3, 2.7 Hz, 1H), 3.59 (dd, J = 15.2,
8.4 Hz, 1H), 3.42 (dd, J = 15.2, 2.7 Hz, 1H), 1.73 (s, 3H); 13C｛1H｝ NMR (100 MHz, Chloroform-d)
δ 168.6, 150.4, 144.5, 142.5, 140.5, 132.2, 131.2, 123.2, 122.4, 118.8, 113.6, 110.6, 109.2, 65.2, 48.6,
43.9, 19.0; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C17H18N2O2Cl, 317.1051; found, 317.1048.
4-(Furan-2-ylmethyl)-7-methyl-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-
5-one
(2c).
Prepared
from
N-(furan-2-ylmethyl)-5-methyl-N-(3-methylbut-2-en-1-yl)-2-nitro-benzamide (29 mg, 0.09 mmol)
and purified following the procedure C; afforded 21.7 mg (83% yield) of the product as a light
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yellow oil: Rf = 0.56 (2:1 PE/EA); H NMR (400 MHz, Chloroform-d) δ 7.61 (s, 1H), 7.40 (s, 1H),
7.08 (d, J = 8.0 Hz, 1H), 6.60 (d, J = 8.1 Hz, 1H), 6.37 (s, 2H), 5.09 (d, J = 15.3 Hz, 1H), 5.08 (s, 1H),
4.92 (s, 1H), 4.48 (d, J = 15.3 Hz, 1H), 3.96 (dd, J = 8.4, 3.1 Hz, 1H), 3.58 (dd, J = 15.1, 8.4 Hz, 1H),
3.42 (dd, J = 15.0, 3.1 Hz, 1H), 2.29 (s, 3H), 1.73 (s, 3H); 13C｛1H｝ NMR (100 MHz, Chloroform-d)
δ 169.8, 150.8, 145.7, 142.3, 142.2, 133.2, 131.8, 129.0, 122.7, 119.3, 112.7, 110.5, 108.9, 65.4, 48.6,
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43.7, 20.2, 19.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H21N2O2, 297.1598; found,
297.1596.
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4-(Furan-2-ylmethyl)-7-methoxy-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepi
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n-5-one
(2d).
Prepared
from
N-(furan-2-ylmethyl)-5-methoxy-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (150 mg, 0.44
mmol) and purified following the procedure C; afforded 111.3 mg (81% yield) of the product as a
light yellow oil: Rf = 0.5 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.39 (s, 1H), 7.32 (d, J =
3.0 Hz, 1H), 6.87 (dd, J = 8.7, 3.0 Hz, 1H), 6.62 (d, J = 8.7 Hz, 1H), 6.35 (s, 2H), 5.08 (d, J = 15.3 Hz,
1H), 5.04 (s, 1H), 4.90 (s, 1H), 4.47 (d, J = 15.3 Hz, 1H), 3.94 (dd, J = 8.3, 3.4 Hz, 1H), 3.88 (s, 1H),
3.79 (s, 3H), 3.55 (dd, J = 15.1, 8.3 Hz, 1H), 3.40 (dd, J = 15.1, 3.5 Hz, 1H), 1.71 (s, 3H); 13C｛1H｝
NMR (100 MHz, Chloroform-d) δ 169.5, 153.4, 150.7, 145.6, 142.3, 138.4, 124.1, 121.0, 120.3, 114.2,
112.6, 110.5, 108.8, 65.5, 55.6, 48.5, 43.7, 19.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C18H21N2O3, 313.1547; found, 313.1546. Larger scale synthesis: Prepared from
N-(furan-2-ylmethyl)-5-methoxy-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (301 mg, 0.88
mmol) and purified following the procedure C; afforded 174.9 mg (64% yield) of 2d.
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8-Fluoro-4-(furan-2-ylmethyl)-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-
5-one
(2e).
Prepared
from
4-fluoro-N-(furan-2-ylmethyl)-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (140 mg, 0.42 mmol)
and purified following the procedure C; afforded 65.5 mg (52% yield) of the product as a light
yellow oil: Rf = 0.6 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.83 (dd, J = 8.7, 6.9 Hz, 1H),
7.39 (s, 1H), 6.55 (td, J = 8.6, 2.3 Hz, 1H), 6.35-6.34 (m, 2H), 6.32 (d, J = 2.3 Hz, 1H), 5.11 (d, J =
15.3 Hz, 1H), 5.03 (s, 1H), 4.94 (s, 1H), 4.40 (d, J = 15.3 Hz, 1H), 3.91 (dd, J = 8.3, 2.2 Hz, 1H), 3.90
(s, 1H), 3.58 (dd, J = 15.1, 8.3 Hz, 1H), 3.43 (dd, J = 15.1, 2.2 Hz, 1H), 1.72 (s, 3H); 13C｛1H｝ NMR
(100 MHz, Chloroform-d) δ 168.7, 165.4 (d, J = 249.0 Hz), 150.6, 146.5 (d, J = 11.0 Hz), 145.1, 142.5,
135.0 (d, J = 10.0 Hz), 118.0 (d, J = 2.0 Hz), 113.2, 110.6, 109.1, 106.8 (d, J = 22.0 Hz), 104.7 (d, J =
24.0 Hz), 65.0, 48.7, 43.9, 19.3; HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C17H17N2O2FNa,
323.1166; found, 323.1169.
2-(Prop-1-en-2-yl)-4-(thiophen-2-ylmethyl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one
(2f). Prepared from N-(3-methylbut-2-en-1-yl)-2-nitro-N-(thiophen-2-ylmethyl)benzamide (39 mg,
0.118 mmol) and purified following the procedure C; afforded 22.9 mg (65% yield) of the product
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as a light yellow oil: Rf = 0.6 (2:1 PE/EA); H NMR (400 MHz, Chloroform-d) δ 7.83 (dd, J = 7.6,
0.9 Hz, 1H), 7.26-7.22 (m, 2H), 7.03 (d, J = 3.1 Hz, 1H), 6.95 (dd, J = 4.9, 3.6 Hz, 1H), 6.90 (t, J = 7.5
Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 5.14 (d, J = 15.1 Hz, 1H), 5.05 (s, 1H), 4.92 (s, 1H), 4.68 (d, J = 15.1
Hz, 1H), 4.02 (dd, J = 8.3, 3.1 Hz, 1H), 3.52 (dd, J = 15.1, 8.3 Hz, 1H), 3.37 (dd, J = 15.1, 3.1 Hz, 1H),
1.70 (s, 3H); 13C｛1H｝ NMR (100 MHz, Chloroform-d) δ 169.6, 145.2, 144.5, 139.7, 132.5, 132.1,
127.0, 126.7, 125.8, 122.3, 119.6, 119.2, 113.2, 65.4, 48.5, 46.1, 19.4; HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C17H19N2OS, 299.1213; found, 299.1211.
9-Chloro-2-(prop-1-en-2-yl)-4-(thiophen-2-ylmethyl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazep
in-5-one
(2g).
Prepared
from
3-chloro-N-(3-methylbut-2-en-1-yl)-2-nitro-N-(thiophen-2-ylmethyl)benzamide (35 mg, 0.096
mmol) and purified following the procedure C; afforded 18.8 mg (59% yield) of the product as a
light yellow oil: Rf = 0.4 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.76 (dd, J = 7.8, 1.3 Hz,
1H), 7.41 (dd, J = 7.8, 1.3 Hz, 1H), 7.28 (s, 1H), 7.05 (d, J = 2.9 Hz, 1H), 6.97 (dd, J = 4.9, 3.6 Hz, 1H),
6.79 (t, J = 7.8 Hz, 1H), 5.20 (d, J = 15.1 Hz, 1H), 5.12 (s, 1H), 4.96 (s, 1H), 4.66 (d, J = 15.1 Hz, 1H),
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4.06 (dd, J = 8.2, 2.7 Hz, 1H), 3.56 (dd, J = 15.2, 8.2 Hz, 1H), 3.38 (dd, J = 15.2, 2.7 Hz, 1H), 1.72 (s,
3H); 13C ｛1H ｝ NMR (100 MHz, Chloroform-d) δ 167.5, 143.3, 139.5, 138.2, 131.2, 130.2, 126.1,
125.7, 124.9, 122.3, 121.4, 117.9, 112.7, 64.3, 47.5, 45.2, 17.9; HRMS (ESI-TOF) m/z: [M + H]+
calcd for C17H18N2OClS, 333.0823; found, 333.0820.
7-Methyl-2-(prop-1-en-2-yl)-4-(thiophen-2-ylmethyl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazep
in-5-one
(2h).
Prepared
from
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5-methyl-N-(3-methylbut-2-en-1-yl)-2-nitro-N-(thiophen-2-ylmethyl)benzamide (36 mg, 0.105
mmol) and purified following the procedure C; afforded 20.9 mg (64% yield) of the product as a
light yellow oil: Rf = 0.5 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.62 (s, 1H), 7.25 (d, J =
8.1 Hz, 1H), 7.07-7.03 (m, 2H), 6.96 (t, J = 8.1 Hz, 1H), 6.58 (d, J = 8.1 Hz, 1H), 5.13 (d, J = 15.1 Hz,
1H), 5.08 (s, 1H), 4.91 (s, 1H), 4.68 (d, J = 15.1 Hz, 1H), 4.00 (dd, J = 8.2, 3.2 Hz, 1H), 3.52 (dd, J =
15.1, 8.2 Hz, 1H), 3.36 (dd, J = 15.1, 3.2 Hz, 1H), 2.28 (s, 3H), 1.70 (s, 3H); 13C｛1H｝ NMR (100
MHz, Chloroform-d) δ 169.8, 145.5, 142.2, 139.8, 133.3, 131.8, 129.1, 126.8, 126.6, 125.7, 122.7,
119.4, 112.9, 65.5, 48.5, 46.0, 20.3, 19.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H21N2OS,
313.1369; found, 313.1367.
9-Methyl-2-(prop-1-en-2-yl)-4-(thiophen-2-ylmethyl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazep
in-5-one
(2i).
Prepared
from
3-methyl-N-(3-methylbut-2-en-1-yl)-2-nitro-N-(thiophen-2-ylmethyl)benzamide (31 mg, 0.09
mmol) and purified following the procedure C; afforded 19.1 mg (68% yield) of the product as a
light yellow oil: Rf = 0.5 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.71 (dd, J = 7.8, 0.8 Hz,
1H), 7.25 (dd, J = 5.1, 0.8 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.03 (d, J = 2.9 Hz, 1H), 6.96 (dd, J = 5.0,
3.5 Hz, 1H), 6.79 (t, J = 7.6 Hz, 1H), 5.23 (d, J = 15.1 Hz, 1H), 5.10 (s, 1H), 4.94 (s, 1H), 4.61 (d, J =
15.1 Hz, 1H), 4.02 (dd, J = 7.6, 2.9 Hz, 1H), 3.68 (s, 1H), 3.57 (dd, J = 15.1, 7.6 Hz, 1H), 3.37 (dd, J =
15.1, 2.9 Hz, 1H), 2.19 (s, 3H), 1.71 (s, 3H); 13C｛1H｝ NMR (150 MHz, Chloroform-d) δ 169.9,
145.1, 142.5, 139.8, 133.4, 130.3, 126.9, 126.6, 125.7, 124.7, 122.6, 118.9, 113.3, 65.2, 48.5, 46.2, 19.1,
18.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H21N2OS, 313.1369; found, 313.1368.
2-(Prop-1-en-2-yl)-4-(2-(pyridin-2-yl)ethyl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one
(2j). Prepared from N-(3-methylbut-2-en-1-yl)-2-nitro-N-(2-(pyridin-2-yl)ethyl)benzamide (49 mg,
0.14 mmol) and purified following the procedure C; afforded 27.9 mg (63% yield) of the product
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as a light yellow oil: Rf = 0.6 (EA); H NMR (400 MHz, Chloroform-d) δ 8.55 (d, J = 4.9 Hz, 1H),
7.76 (dd, J = 7.8, 1.6 Hz, 1H), 7.63 (td, J = 7.6, 1.6 Hz, 1H), 7.29 (s, 1H), 7.23 (td, J = 7.6, 1.6 Hz, 1H),
7.16 (t, J = 5.0 Hz, 1H), 6.87 (td, J = 7.5,1.0 Hz, 1H), 6.63 (d, J = 8.0 Hz, 1H), 5.05 (s, 1H), 4.90 (s,
1H), 4.05–4.02 (m, 1H), 3.99 (dd, J = 8.3, 3.1 Hz, 1H), 3.88-3.81 (m, 1H),, 3.48 (dd, J = 15.0, 8.3 Hz,
1H), 3.29 (dd, J = 15.0, 3.1 Hz, 1H), 3.24–3.10 (m, 2H), 1.71 (s, 3H); 13C｛1H｝ NMR (100 MHz,
Chloroform-d) δ 168.8, 158.1, 148.1, 144.4, 143.6, 135.8, 131.2, 130.7, 123.0, 122.0, 120.6, 118.6,
118.1, 112.1, 64.8, 49.2, 48.3, 35.7, 18.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C19H22N3O,
308.1757; found, 308.1755.
2-(Prop-1-en-2-yl)-4-(2-(thiophen-2-yl)ethyl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-on
e (2k). Prepared from N-(3-methylbut-2-en-1-yl)-2-nitro-N-(2-(thiophen-2-yl)ethyl)benzamide (42
mg, 0.12 mmol) and purified following the procedure C; afforded 31.6 mg (83% yield) of the
product as a light yellow oil: Rf = 0.48 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.78 (dd,
J = 7.8, 1.3 Hz, 1H), 7.24 (dd, J = 7.2, 1.3 Hz, 1H), 7.16 (d, J = 5.1 Hz, 1H), 6.95-6.87 (m, 3H), 6.67 (d,
J = 8.0 Hz, 1H), 5.08 (s, 1H), 4.93 (s, 1H), 3.99 (dd, J = 8.1, 2.8 Hz, 1H), 3.96–3.88 (m, 1H), 3.70-3.63
(m, 1H), 3.46 (dd, J = 15.1, 8.1 Hz, 1H), 3.30–3.13 (m, 2H), 3.25 (dd, J = 15.1, 2.8 Hz, 1H), 1.72 (s,
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3H); 13C ｛1H ｝ NMR (100 MHz, Chloroform-d) δ 168.7, 144.2, 143.6, 140.6, 131.3, 130.7, 126.0,
124.5, 122.8, 122.0, 118.6, 118.1, 112.2, 64.7, 50.5, 49.5, 27.6, 18.3; HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C18H21N2OS, 313.1369; found, 313.1367.
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9-Chloro-2-(prop-1-en-2-yl)-4-(2-(thiophen-2-yl)ethyl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diaze
pin-5-one
(2l).
Prepared
from
3-chloro-N-(3-methylbut-2-en-1-yl)-2-nitro-N-
(2-(thiophen-2-yl)ethyl)benzamide (51 mg, 0.135 mmol) and purified following the procedure C;
afforded 24.8 mg (53% yield) of the product as a light yellow oil: Rf = 0.42 (2:1 PE/EA); 1H NMR
(400 MHz, Chloroform-d) δ 7.70 (dd, J = 7.9, 1.5 Hz, 1H), 7.40 (dd, J = 7.8, 1.5 Hz, 1H), 7.17 (dd, J =
5.0, 0.8 Hz, 1H), 6.98–6.92 (dd, J = 5.0, 3.0 Hz, 1H), 6.88 (d, J = 3.0 Hz, 1H), 6.79 (t, J = 7.8 Hz, 1H),
5.13 (s, 1H), 4.96 (s, 1H), 4.53 (s, 1H), 4.05 (dd, J = 8.1, 2.4 Hz, 1H), 3.98–3.85 (m, 1H), 3.71-3.64 (m,
1H), 3.48 (dd, J = 15.2, 8.1 Hz, 1H), 3.30-3.13 (m, 2H), 3.20 (dd, J = 15.2, 2.4 Hz, 1H), 1.73 (s, 3H);
13C｛1H｝ NMR (100 MHz, Chloroform-d) δ 167.8, 143.3, 140.4, 139.5, 131.1, 129.8, 126.1, 124.6,
123.0, 122.9, 121.5, 118.1, 112.8, 64.6, 50.7, 49.5, 27.5, 17.9; HRMS (ESI-TOF) m/z:[M + H]+ calcd
for C18H20N2OClS, 347.0979; found, 347.0977.
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7-Methyl-2-(prop-1-en-2-yl)-4-(2-(thiophen-2-yl)ethyl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diaze
pin-5-one
(2m).
Prepared
from
5-methyl-N-(3-methylbut-2-en-1-yl)-2-nitro-N-(2-(thiophen-2-yl)ethyl) benzamide (25 mg, 0.07
mmol) and purified following the procedure C; afforded 12.3 mg (54% yield) of the product as a
light yellow oil: Rf =0.4(2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.56 (s, 1H), 7.14 (dd, J =
5.0, 0.7 Hz, 1H), 7.05 (dd, J = 8.0, 1.6 Hz, 1H), 6.92 (dd, J = 5.0, 3.5 Hz, 1H), 6.87 (d, J = 2.9 Hz, 1H),
6.63 (d, J = 8.0 Hz, 1H), 5.06 (s, 1H), 4.90 (s, 1H), 3.98 (dd, J = 8.1, 3.1 Hz, 1H), 3.92–3.82 (m, 1H),
3.71-3.64 (m, 1H), 3.41 (dd, J = 15.1, 8.3 Hz, 1H), 3.20 (dd, J = 15.1, 3.1 Hz, 1H), 3.27-3.11, (m, 2H),
2.27 (s, 3H), 1.69 (s, 3H); 13C｛1H｝ NMR (150 MHz, Chloroform-d) δ 169.8, 144.9, 141.6, 133.1,
131.5, 129.9, 127.0, 125.5, 125.4, 123.8, 119.7, 113.3, 112.5, 65.8, 51.4, 50.4, 28.6, 20.3, 19.5; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C19H23N2OS, 327.1526; found, 327.1522.
4-Benzyl-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one (2n). Prepared
from N-benzyl-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (43 mg, 0.133 mmol) and purified
following the procedure C; afforded 34.9 mg (90% yield) of the product as a yellow viscous liquid:
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Rf = 0.5 (2:1 PE/EA); H NMR (400 MHz, Chloroform-d) δ 7.85 (dd, J = 7.8, 1.1 Hz, 1H),
7.35-7.23 (m, 6H), 6.89 (t, J = 7.5 Hz, 1H), 6.66 (d, J = 8.0 Hz, 1H), 5.05 (d, J = 14.8 Hz,
1H),5.02 (s, 1H), 4.89 (s, 1H), 4.54 (d, J = 14.8 Hz, 1H), 3.95 (dd, J = 8.4, 2.9 Hz, 1H), 3.80 (s,
1H), 3.51 (dd, J = 15.1, 8.4 Hz, 1H), 3.28 (dd, J = 15.1, 2.9 Hz, 1H), 1.65 (s, 3H); 13C｛1H｝
NMR (150 MHz, Chloroform-d) δ 169.9, 145.4, 144.5, 137.2, 132.3, 132.0, 128.7, 128.3, 127.5,
122.6, 119.5, 119.1, 112.9, 65.3, 51.3, 48.6, 19.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C19H21N2O, 293.1648; found, 293.1646.
4-Benzyl-9-methyl-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one
(2o).Prepared from N-benzyl-3-methyl-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (32 mg,
0.095 mmol) and purified following the procedure C; afforded 15.4 mg (53% yield) of the product
as a thick yellow oily liquid: Rf = 0.6 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.73 (d, J =
7.7 Hz, 1H), 7.35–7.28 (m, 5H), 7.20 (d, J = 7.7 Hz, 1H), 6.82 (t, J = 7.6 Hz, 1H), 5.07 (d, J = 14.8 Hz,
1H), 5.06 (s, 1H), 4.91 (s, 1H), 4.54 (d, J = 14.8 Hz, 1H), 4.09–3.90 (m, 1H), 3.52 (dd, J = 15.0, 8.0 Hz,
1H), 3.27 (dd, J = 15.0, 2.8 Hz, 1H), 2.21 (s, 3H), 1.66 (s, 3H); 13C｛1H｝ NMR (100 MHz,
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Chloroform-d) δ 170.2, 145.1, 142.2, 137.2, 133.4, 130.3, 128.7, 128.4, 127.5, 124.9, 123.0, 119.1,
113.3, 65.1, 51.4, 48.4, 19.1, 18.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C20H23N2O,
307.1805; found, 307.1803.
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5-(2,6-Dimethylbenzyl)-9-methyl-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepi
n-5-one (2p). Prepared from
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N-(2,6-dimethylbenzyl)-3-methyl-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (42 mg, 0.115
mmol) and purified following the procedure C; afforded 31.8 mg (83% yield) of the product as a
light yellow oil: Rf = 0.44 (4:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.71 (d, J = 7.7 Hz,
1H), 7.39–7.31 (m, 1H), 7.19–7.12 (m, 1H), 7.06 (d, J = 7.4 Hz, 2H), 6.79 (t, J = 7.6 Hz, 1H), 5.23 (d,
J = 14.6 Hz, 1H), 4.77 (d, J = 13.8 Hz, 2H), 4.70 (d, J = 14.6 Hz, 1H), 3.69 (dd, J = 9.7, 2.8 Hz, 2H),
3.39 (dd, J = 14.9, 9.7 Hz, 1H), 2.93 (dd, J = 14.9, 2.8 Hz, 1H), 2.38 (s, 6H), 2.18 (s, 3H), 1.41 (s, 3H);
13C｛1H｝ NMR (100 MHz, Chloroform-d) δ 170.0, 146.0, 142.3, 138.5, 133.4, 132.1, 130.4, 128.6,
127.9, 124.5, 122.7, 118.7, 112.6, 65.8, 47.0, 43.8, 20.2, 18.7, 18.3; HRMS (ESI-TOF) m/z: [M + H]+
calcd for C22H27N2O, 335.2118; found, 335.2124.
4,9-Dimethyl-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one
(2q).
Prepared from N,3-dimethyl-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (60 mg, 0.229 mmol)
and purified following the procedure C; afforded 34.8 mg (66% yield) of the product as a yellow
solid: Rf = 0.35 (2:1 PE/EA), mp 132-134 oC; 1H NMR (400 MHz, Chloroform-d) δ 7.60 (dd, J = 7.7,
0.8 Hz, 1H), 7.16 (d, J = 7.2 Hz, 1H), 6.78 (t, J = 7.6 Hz, 1H), 5.21 (s, 1H), 4.98 (s, 1H), 4.22 (dd, J =
6.7, 3.1 Hz, 1H), 3.56 (dd, J = 15.0, 6.7 Hz, 1H), 3.42 (dd, J = 15.0, 3.1 Hz, 1H), 3.14 (s, 3H), 2.20 (s,
3H), 1.78 (s, 3H); 13C｛1H｝ NMR (100 MHz, Chloroform-d) δ 170.3, 144.9, 142.5, 133.2, 129.9,
124.9, 123.6, 119.2, 113.5, 65.1, 51.1, 36.3, 19.3, 18.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C14H19N2O, 231.1492; found, 231.1491.
4-(4-Fluorophenethyl)-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one
(2r). Prepared from N-(4-fluorophenethyl)-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (150 mg,
0.421 mmol) and purified following the procedure C; afforded 68.3 mg (50% yield) of the product
as a thick yellow liquid: Rf = 0.5 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.76 (dd, J = 7.8,
1.4 Hz, 1H), 7.25-7.18 (m, 3H), 7.00-6.95 (m, 2H), 6.90 (t, J = 7.4 Hz, 1H), 6.68 (d, J = 7.8 Hz, 1H),
5.05 (s, 1H), 4.92 (s, 1H), 4.00 (dd, J = 8.2, 3.2 Hz, 1H), 3.85-3.78 (m, 1H), 3.64-3.57 (m, 1H), 3.41
(dd, J = 15.1, 8.2 Hz, 1H), 3.18 (dd, J = 15.1, 3.2 Hz, 1H), 3.00-2.87 (m, 2H), 1.70 (s, 3H); 13C｛1H｝
NMR (100 MHz, Chloroform-d) δ 169.7, 161.6 (d, J = 242.0 Hz), 145.2, 144.5, 134.9 (d, J = 3.0 Hz),
132.3, 131.7, 130.4 (d, J = 8.0 Hz), 123.2, 119.8, 119.2, 115.4 (d, J = 21.0 Hz), 113.3, 65.8, 51.3, 50.5,
33.7, 19.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C20H22N2OF, 325.1711; found, 325.1708.
4-(4-Fluorophenethyl)-7-methyl-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin
-5-one
(2s).
Prepared
from
N-(4-fluorophenethyl)-5-methyl-N-(3-methylbut-en-1-yl)-2-nitrobenzamide (44 mg, 0.119 mmol)
and purified following the procedure C; Afforded 27.3 mg (68% yield) of the product as a light
yellow oil: Rf = 0.4 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.56 (s, 1H), 7.21 (dd, J = 8.0,
5.6 Hz, 2H), 7.06 (d, J = 7.2 Hz, 1H), 6.98 (t, J = 8.6 Hz, 2H), 6.58 (d, J = 8.1 Hz, 1H), 5.07 (s, 1H),
4.90 (s, 1H), 3.97 (dd, J = 8.1, 3.2 Hz, 1H), 3.88–3.75 (m, 1H), 3.65-3.57 (m, 1H), 3.40 (dd, J = 15.0,
8.1 Hz, 1H), 3.17 (dd, J = 15.0, 3.2 Hz, 1H), 3.01-2.88 (m, 2H), 2.28 (s, 3H), 1.70 (s, 3H); 13C｛1H｝
NMR (100 MHz, Chloroform-d) δ 169.9, 161.6 (d, J = 243.0 Hz), 145.4, 142.1, 134.9 (d, J = 3.0 Hz),
133.1, 131.5, 130.3 (d, J = 8.0 Hz), 129.3, 123.5, 119.4, 115.3 (d, J = 21.0 Hz), 113.1, 65.8, 51.2, 50.4,
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33.7, 20.3, 19.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H24FN2O, 339.1867; found,
339.1867.
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4-(4-Fluorophenethyl)-9-methyl-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin
-5-one (2t). Prepared from N-(4-fluorophenethyl)-3-methyl-N-(3-methylbut-2-en-1-yl)-2-nitro
benzamide (140 mg, 0.378 mmol) and purified following the procedure C; afforded 76.7 mg (60%
yield) of the product as a light yellow oil: Rf = 0.4 (2:1 PE/EA); 1H NMR (600 MHz, Chloroform-d)
δ 7.70–7.61 (m, 1H), 7.56-7.45 (m, 1H), 7.22-7.18 (m, 2H), 6.98 (t, J = 8.4 Hz, 2H), 6.80 (t, J = 7.5 Hz,
1H), 5.11 (s, 1H), 4.94 (s, 1H), 4.03 (dd, J = 7.4, 2.4 Hz, 1H), 3.88-3.84 (m, 1H), 3.59-3.54 (m, 1H),
3.43 (dd, J = 15.0, 7.4 Hz, 1H), 3.21 (dd, J = 15.0, 2.4 Hz, 1H), 2.99-2.89 (m, 2H), 2.19 (s, 3H), 1.71 (s,
3H); 13C｛1H｝ NMR (100 MHz, Chloroform-d) δ 170.1, 161.6 (d, J = 243.0 Hz), 145.0, 142.5, 135.0
(d, J = 3.0 Hz), 133.3, 130.3 (d, J = 8.0 Hz), 130.0, 125.0, 123.6, 119.2, 115.4 (d, J = 21.0 Hz), 113.5,
65.6, 51.3, 50.3, 33.7, 19.1, 18.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H24N2OF,
339.1867; found, 339.1868.
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4-(Furan-2-ylmethyl)-2-methyl-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-
5-one (2u). Prepared from N-(2,3-dimethylbut-2-en-1-yl)-N-(furan-2-ylmethyl)-2-nitrobenzamide
(47 mg, 0.143 mmol) and purified following the procedure C; afforded 33.9 mg (80% yield) of the
product as a light yellow oil: Rf = 0.43 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.77 (dd,
J =7.8, 1.2 Hz, 1H), 7.34 (d, J = 1.2 Hz, 1H), 7.29–7.17 (m, 1H), 6.92 (t, J = 7.5 Hz, 1H), 6.67 (d, J =
7.7 Hz, 1H), 6.32-6.27 (m, 2H), 5.36 (s, 1H), 5.10 (d, J = 15.4 Hz, 1H), 5.00 (s, 1H), 4.30 (d, J = 15.4
Hz, 1H), 3.46 (d, J = 15.3 Hz, 1H), 3.28 (d, J = 15.3 Hz, 1H), 1.85 (s, 3H), 1.29 (s, 3H); 13C｛1H｝
NMR (150 MHz, Chloroform-d) δ 169.8, 151.1, 147.1, 142.2, 132.1, 131.6, 124.5, 120.6, 120.3, 114.1,
110.4, 108.6, 67.2, 52.1, 43.8, 24.9, 19.8; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H21N2O2,
297.1598; found, 297.1595.
4-(2,6-Dimethylbenzyl)-9-methyl-2-vinyl-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one
(2v).
Prepared
from
N-(2,6-dimethylbenzyl)-3-methyl-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (70 mg, 0.199
mmol) and purified following the procedure C; afforded 47.7 mg (75% yield) of the product as a
light yellow oil: Rf = 0.4 (4:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.66 (d, J = 7.7 Hz, 1H),
7.20 (d, J = 7.3 Hz, 1H), 7.13 (d, J = 7.0 Hz, 1H), 7.06 (d, J = 7.4 Hz, 2H), 6.89 (t, J = 7.5 Hz, 1H),
5.66-5.57 (m, 1H), 5.21 (d, J = 14.6 Hz, 1H), 5.02–4.95 (m, 2H), 4.73 (d, J = 14.5 Hz, 1H), 3.74 (br,
1H), 3.24 (dd, J = 15.0, 9.8 Hz, 1H), 2.96 (dd, J = 15.0, 3.6 Hz, 1H), 2.39 (s, 6H), 2.20 (s, 3H); 13C｛
1H｝ NMR (150 MHz, Chloroform-d) δ 170.4, 138.9, 138.1, 133.5, 132.8, 129.9, 128.9, 128.9, 128.2,
126.3, 125.8, 120.5, 117.0, 64.6, 47.9, 44.0, 20.6, 18.5; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C21H25N2O, 321.1961; found, 321.1969.
4-(Furan-2-ylmethyl)-2-vinyl-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one (2w). Prepared
from (E)-N-(but-2-en-1-yl)-N-(furan-2-ylmethyl)-2-nitrobenzamide (41 mg, 0.137 mmol) and
purified following the procedure C; afforded 28.9 mg (79% yield) of the product as a light yellow
oil: Rf =0.42 (2:1 PE/EA); 1H NMR (400 MHz, Chloroform-d) δ 7.78 (dd, J = 7.7, 1.0 Hz, 1H), 7.37 (s,
1H), 7.29-7.20 (m, 2H), 6.92 (t, J = 7.5 Hz, 1H), 6.71 (d, J = 7.9 Hz, 1H), 6.34 (s, 1H), 5.80 (td, J =
17.0, 10.2 Hz, 1H), 5.27 (d, J = 17.0 Hz, 1H), 5.16 (d, J = 10.2 Hz, 1H), 5.01 (d, J = 15.3 Hz, 1H), 4.54
(d, J = 15.3 Hz, 1H), 4.06 (q, J = 5.8 Hz, 1H), 3.46 (d, J = 5.8 Hz, 2H); 13C｛1H｝ NMR (100 MHz,
Chloroform-d) δ 169.5, 150.8, 142.9, 142.3, 136.8, 132.3, 131.8, 123.8, 120.7, 120.0, 117.3, 110.6,
108.9, 62.9, 49.5, 44.0; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H17N2O2, 269.1285; found,
269.1292.
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4-(4-Methoxyphenyl)-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one
(2x). Prepared from N-(4-methoxyphenyl)-N-(3-methylbut-2-en-1-yl)-2-nitrobenzamide (130 mg,
0.382 mmol) and purified following the procedure C; afforded 62.4 mg (53% yield) of the product
as a white solid: Rf = 0.5 (2:1 PE/EA), mp 165-167 oC; 1H NMR (400 MHz, Chloroform-d) δ 7.82 (d,
J = 7.8 Hz, 1H), 7.31-7.28 (m, 3H), 6.94-6.92 (m, 3H), 6.84 (d, J = 6.4 Hz, 1H), 5.15 (s, 1H), 4.95 (s,
1H), 4.32 (dd, J = 8.3, 3.0 Hz, 1H), 3.99 (dd, J = 14.9, 8.3 Hz, 1H), 3.82 (s, 3H), 3.76 (dd, J = 14.9, 3.0
Hz, 1H), 1.64 (s, 3H); 13C｛1H｝ NMR (100 MHz, Chloroform-d) δ 169.8, 158.1, 145.1, 144.7, 136.6,
132.6, 132.2, 127.8, 123.0, 119.8, 119.2, 114.5, 113.4, 65.6, 55.5, 52.4, 19.2; HRMS (ESI-TOF) m/z:
[M + H]+ calcd for C19H21O2N2, 309.1598; found, 309.1595.
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2-(Prop-1-en-2-yl)-4-(m-tolyl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one (2y). Prepared
from N-(3-methylbut-2-en-1-yl)-2-nitro-N-(m-tolyl)benzamide (38 mg, 0.117 mmol) and purified
following the procedure C; afforded 17.5 mg (51% yield) of the product as a light yellow oil: Rf =
1
0.4 (2:1 PE/EA); H NMR (400 MHz, Chloroform-d) δ 7.83 (d, J = 7.7 Hz, 1H), 7.31-7.28 (m, 2H),
7.17-7.13 (m, 2H), 7.09 (d, J = 7.5 Hz, 1H), 6.92 (t, J = 7.4 Hz, 1H), 6.74 (d, J = 7.9 Hz, 1H), 5.13 (s,
1H), 4.93 (s, 1H), 4.32 (dd, J = 8.6, 2.7 Hz, 1H), 4.02 (dd, J = 14.9, 8.6 Hz, 1H), 3.78 (dd, J = 14.9, 2.7
Hz, 1H), 2.37 (s, 3H), 1.64 (s, 3H); 13C｛1H｝ NMR (150 MHz, Chloroform-d) δ 169.6, 145.0, 144.4,
143.4, 139.1, 132.6, 132.1, 129.0, 127.6, 127.3, 123.5, 123.0, 119.9, 119.3, 113.5, 65.5, 52.1, 21.4, 19.2;
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C19H21N2O, 293.1648; found, 293.1651.
4-Phenyl-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diazepin-5-one (2z). Prepared
from N-(3-methylbut-2-en-1-yl)-2-nitro-N-phenylbenzamide (29 mg, 0.094 mmol) and purified
following the procedure C; afforded 13.3 mg (51% yield) of the product as a white solid: Rf = 0.43
o
1
(2:1 PE/EA), mp 167-169 C; H NMR (400 MHz, Chloroform-d) δ 7.82 (dd, J = 7.8, 1.4 Hz, 1H),
7.41 (t, J = 7.7 Hz, 2H), 7.34 (d, J = 7.2 Hz, 2H), 7.31–7.25 (m, 2H), 6.90 (t, J = 7.4 Hz, 1H), 6.71 (d, J
= 8.0 Hz, 1H), 5.15 (s, 1H), 4.93 (s, 1H), 4.30 (dd, J = 8.2, 3.0 Hz, 1H), 4.04 (dd, J = 14.9, 8.2 Hz, 1H),
3.93 (s, 1H), 3.82 (dd, J = 14.9, 3.0 Hz, 1H), 1.62 (s, 3H); 13C｛1H｝ NMR (100 MHz, Chloroform-d)
δ 169.7, 145.0, 144.7, 143.5, 132.7, 132.2, 129.2, 126.7, 126.6, 122.9, 119.8, 119.2, 113.6, 65.5, 52.0,
19.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C18H19ON2, 279.1492; found, 279.1490.
(E)-4-Benzyl-9-methyl-2-(6-methylhepta-2,5-dien-2-yl)-1,2,3,4-tetrahydro-5H-benzo[e][1,4]diaz
epin-5-one
(2a1).
Prepared
from
(E)-N-benzyl-N-(3,7-dimethylocta-2,6-dien-1-yl)-3-methyl-2-nitrobenzamide (37 mg, 0.091 mmol)
and purified following the procedure C; afforded 16.7 mg (49% yield) of the product as a light
1
yellow oil: Rf = 0.6 (2:1 PE/EA); H NMR (400 MHz, Chloroform-d) δ 7.71 (d, J = 7.1 Hz, 1H),
7.34-7.28 (m, 5H), 7.18 (d, J = 7.1 Hz, 1H), 6.80 (t, J = 7.5 Hz, 1H), 5.42 (t, J = 7.0 Hz, 1H), 5.06 (t, J
= 7.1 Hz, 1H), 4.96 (d, J = 14.7 Hz, 1H), 4.60 (d, J = 14.8 Hz, 1H), 3.98 (dd, J = 8.4, 2.7 Hz, 1H), 3.55
(dd, J = 15.0, 8.4 Hz, 1H), 3.21 (dd, J = 15.0, 2.7 Hz, 1H), 2.69 (t, J = 7.0 Hz, 2H), 2.18 (s, 3H), 1.70 (s,
3H), 1.63 (s, 3H), 1.55 (s, 3H); 13C｛1H｝ NMR (100 MHz, Chloroform-d) δ 170.3, 142.8, 137.3,
134.8, 133.3, 132.4, 130.3, 128.6, 128.3, 127.5, 126.8, 124.7, 122.7, 121.9, 118.7, 66.9, 51.3, 48.7, 26.7,
25.7, 18.3, 17.8, 13.0; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C25H31N2O, 375.2431; found,
375.2438.
Preparation of deuterated compound 1aa’. See S94 in the SI. Compounds b, c, d, e, f were
obtained according to the referenece.37 Preparation method of compound 1aa’ was consistent with
the procedure of compound 1aa.
Supporting Information.
Concise list of types of data or files found in the SI: 1H and 13C｛1H｝ NMR Spectra, additional
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reaction schemes, X-ray single crystal data and CIF file, larger scale reaction schemes.
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Acknowledgment
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We gratefully acknowledge the financial support from the Sichuan University–Lu Zhou
Strategic Cooperation Projects (No. 2017 CDLZ-S34) and the 111 Project.
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