A catalyst-free four-component domino reaction for the synthesis of functionalized 3-acyl-1,5-benzodiazepines

Article abstract of DOI:10.1039/c8ob02903b

Various functional 3-acyl-1,5-benzodiazepines containing carboxyl, ester and acyl groups at the 2-position were synthesized via an efficient, sustainable and catalyst-free domino reaction. During the synthesis process, one new cycle and four new bonds (on

Full text of DOI:10.1039/c8ob02903b

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A catalyst-free four-component domino
reaction for the synthesis of functionalized
Cite this: DOI: 10.1039/c8ob02903b
3-acyl-1,5-benzodiazepines†
Yue-Wei Sun,
Yue-Ming Bei and Lan-Zhi Wang
*
Various functional 3-acyl-1,5-benzodiazepines containing carboxyl, ester and acyl groups at the 2-posi-
tion were synthesized via an efficient, sustainable and catalyst-free domino reaction. During the synthesis
process, one new cycle and four new bonds (one C–C, two C–N and one CvC) were constructed by the
nucleophilic substitution, nucleophilic addition, dehydration and cyclization reaction by the H+ shift.
Furthermore, a total of 26 examples were examined by reacting inexpensive starting materials of N,N-di-
methylformamide dimethyl acetal, aromatic ketones, 1,2-phenylenediamine compounds and aldehyde
derivatives. Therefore, it displayed a broad substrate scope, good functional group tolerance, high yields
(77–97%) and the ease of obtaining target compounds without the involvement of toxic solvents and
column chromatography, which provided a novel method for the synthesis of a wide variety of biologically
relevant 1,5-benzodiazepines.
Received 21st November 2018,
Accepted 3rd January 2019
DOI: 10.1039/c8ob02903b
rsc.li/obc
The introduction of the pharmacological and physiological
Introduction
active groups including –COOR,10 –COOH, –COR11 on the
Carbon–carbon and carbon–nitrogen bonds are ubiquitously seven-membered ring can bring about some remarkable
present in most of the natural and synthetic organic mole- changes in the reactivity and activity of the new 1,5-benzo-
cules, particularly in nitrogen-containing heterocycle frame- diazepins. As far as we know, 1,5-benzodiazepines contain-
works.1 Benzodiazepines are important classes of nitrogen- ing the ester group are investigated widely. For example,
containing heterocycles with pharmacological activities, which in 2010, Jian-Ping Zou12 et al. developed a novel [4 + 2 + 1]
are broadly used as analgesic, sedative, anticonvulsant, antian- cycloaddition reaction to synthesize a new class of 3,4-di-
xiety and hypnotic agents.2–4 Over 40 medications highlight substituted 1,5-benzodiazepines (Scheme 1A-I). However,
benzodiazepines as a classic privileged structure with a broad there is a paucity of reports on the one-pot procedure for the
range of therapeutic treatments. Recently, the results of synthesis of 3-acyl-1,5-benzodiazepines from readily available
medical research indicated that benzodiazepines could be starting materials. Previously, we have established a mild
extended to various diseases such as cancer, viral infection method for the synthesis of 2-aryl-3-acetyl-1,5-benzodiazepines
and cardiovascular disorders.5 Due to their wide biological (Scheme 1A-II).13 Although this method was proved to be suc-
activity, the synthesis of these compounds has received a great cessful and allowed facile access to 3-acyl-1,5-benzodiazepines,
deal of attention.6 Consequently, the design of novel reactions it suffered from certain disadvantages, such as the need for a
with unprecedented procedures for the synthesis of new highly expensive reagent (3-butyn-2-one) and a limited sub-
classes of benzodiazepine-based molecules, as well as for mul- strate scope, which makes this strategy less adaptable for the
tiple bond (C–C/CvC/C–N) formation using an inexpensive sustainable synthesis. This scenario strongly suggests that
substrate with a simple catalytic system, remains a highly the development of a new methodology, which meets the
desirable and continuous goal in contemporary organic syn- requirements of sustainable chemistry, is still challenging.
thesis.7,8 In this context, one-pot domino reactions have Continuing our effort on the development of new sustainable
emerged as a tool to realize the objective due to their efficient protocols to construct 3-acyl-1,5-benzodiazepines, herein, we
atom economy and green characteristics.9
have developed an efficient and novel approach for the syn-
thesis of highly functionalized 3-acyl-1,5-benzodiazepines 5
(Scheme 1B II) via a domino sequence of a nucleophilic
substitution/nucleophilic addition/dehydration/cyclization/H+
shift. These reactions were achieved by reacting aromatic
ketones 1, N,N-dimethylformamide dimethyl acetal 2, and
College of Chemistry & Material Science, Hebei Normal University,
Shijiazhuang 050024, China. E-mail: wanglanzhi@hebtu.edu.cn
†Electronic supplementary information (ESI) available: IR, MS/MS and NMR
spectra. See DOI: 10.1039/c8ob02903b
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Scheme 1 Synthetic routes to 3-acyl-1,5-benzodiazepines 5.
1,2-phenylenediamine compounds 3 with aldehyde deriva-
tives 4 without using any metal catalysts. These reactions
Results and discussion
showed a broad substrate scope and did not require in- According to the pathway shown in Scheme 2, a stepwise syn-
expensive commercial starting materials. To the best of our thesis of 3-aryl-1,5-benzodiazepine 5aaa was carried out to
knowledge, this is the first report of the synthesis of 3-acyl- search for suitable reaction conditions. Firstly, compound 6a
1,5-benzodiazepines with the ester, carboxyl and acyl groups was synthesized from N,N-dimethylformamide 2 and acetophe-
at the 2-position.
none 1a in an excellent yield of 98% (Scheme 2A).14
Table 1 Optimization of reaction conditionsa
Entry
Temp.
Solvent
Catalysts
Time/h
Yieldb/%
1
2
3
4
5
6
7
8
0 °C
r.t.
78 °C
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
EtOH
EtOH
EtOH
PhMe
MeCN
EtOAc
MeOH
EtOH
EtOH
EtOH
EtOH
—
—
—
—
—
—
—
p-TsOH
L-Pro
HOAc
CeCl3
11
3
1
6
5
7
4.5
2
2.5
1.5
2.5
69
90
44
40
60
65
90
65
63
45
60
9
10
11
r.t.
a Reaction conditions: Compound 6 (1 mol), methylglyoxal (1 mol),
catalyst (5 mol%), solvent (2 mL), unless otherwise mentioned.
b Isolated yield.
Scheme 2 The routes of a stepwise synthesis of 3-acyl-1,5-benzo-
diazepine 5aaa.
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Subsequently, compound 7aa was successfully synthesized because side products were produced by TLC (Table 1, entry 3).
from compound 6a and 1,2-phenylenediamine 3a in an excel- Next, various solvents, such as methanol, ethanol, toluene,
lent yield of 90% (Scheme 2B).15
acetonitrile and ethyl acetate, were employed as reaction
The formation of compound 5aaa can be reckoned as the media. The solvents exhibited great influence on the reaction
crucial step for this work. In order to obtain a high yield of the rate. Among these solvents, the protic solvents resulted in
target compound 5aaa, the reaction of compound 7aa and product 5aaa in higher isolated yields. Methanol gave good
methylglyoxal 4a was selected as the model reaction yields but needed longer reaction time than ethanol (Table 1,
(Scheme 2C). The above model reaction was conducted to entries 2 and 7). In terms of yield and reactivity, ethanol was
investigate the impact of various reaction conditions on the the most suitable reaction medium. A lower yield of product
reaction outcome, including catalysts, solvents and tempera- 5aaa was obtained when the reaction was performed in
ture. These results are listed in Table 1.
different aprotic solvents (Table 1, entries 4–6). Finally, the
To begin with, the effect of the reaction temperature was catalyst was examined. The reaction was proceeded smoothly
examined (Table 1, entries 1–3). A screening of different reac- without acidic promoters to give 1,5-benzodiazepine 5aaa in
tion temperatures showed that the reaction gave the best result excellent yield (Table 1, entry 2). Then, different acids were
at room temperature (Table 1, entry 2). Decreasing reaction screened for this reaction. Unfortunately, when various acidic
temperature slowed down the reaction rate (Table 1, entry 1). catalysts were evaluated as potential promoters for this reac-
Increasing the reaction temperature decreased the yield tion, the desired product was obtained only in yields of 45%–
65% (Table 1, entries 8–11). Consequently, the following reac-
tion conditions are recommended: catalyst-free in ethanol at
room temperature (Table 1, entry 2).
With the optimized reaction conditions in hand, we
attempted a green domino process for the one-pot synthesis of
1,5-benzodiazepine 5aaa (Scheme 3) of N,N-dimethyl-
formamide dimethyl acetal 2, acetophenone 1a, 1,2-phenylene-
diamine 3a and methylglyoxal 4a. To our delight, this domino
reaction proceeded smoothly to give 1,5-benzodiazepine 5aaa
Scheme 3 One-pot synthesis of 1,5-benzodiazepine via
reaction.
a domino
Table 2 Scope of 1,2-phenylenediamin and aldehyde derivatives for one-pot synthesis of benzodiazepinesa
a Reaction conditions: N,N-Dimethylformamide dimethyl acetal (1 mmol), acetophenone (1 mmol), 1,2-phenylenediamine compounds (1 mmol),
and aldehyde derivatives (1 mmol) in EtOH (2 ml), reflux to rt.
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in good yield (84%). This encouraging result indicated the tion of acetophenone, the expected products 5caa–5daa and
feasibility of the envisioned domino reaction. 5cbb–5dbb were also achieved in good yields of 77–92%.
Therefore, the generality and limitation of this domino Pleasingly, acetophenone with a strong electron withdrawing
approach were examined. Initially, we evaluated the reaction group on the phenyl ring, such as –NO2, afforded the 1,5-
scope with different substituted 1,2-phenylenediamines 3a–e. benzodiazepines 5eaa and 5ebb in yields of 83–95%.
As shown in Table 2, the different substituted 1,2-phenylene- Encouraged by these results, we decided to further explore the
diamine compounds were well tolerated. These reactions gave scope of aromatic ketone derivatives. 2-Acetylthiazole 1f and
good to excellent yields of desired product 5. Importantly, we 2-acetylpyridine 1g were desirable substrates for this reaction
observed that electron-rich 1,2-phenylenediamine compounds to afford the corresponding products 5fab–5gab and 5fac–5gac
were more reactive. Thus, these reactions gave better yields in excellent yields of 89–95%. This result can be attributed to
than those possessing electron withdrawing groups. Then, as higher reactivity of 2-acetylthiazole 1f and 2-acetylpyridine 1g
an extension of the above study, we chose a variety of aldehyde than that of acetophenone 1a.
derivatives 4a–c to react to investigate the possibility of this
As summarized in Tables 2 and 3, this new domino
reaction. As anticipated, these reactions proceeded smoothly approach tolerates a wide range of substituents on the 1,5-
to give corresponding 1,5-benzodiazepines in good to excellent benzodiazepines. The functional groups include carboxyl,
yields.
ester and acyl groups at the 2-position on the seven-membered
Furthermore, we set out to explore the scope with different ring, and a series of aryl groups on the 3-acyl and various sub-
aromatic ketone derivatives 1 (Table 3). From the results, when stituents on the benzene ring.
4′-methylacetophenone 1b bearing electron donating groups
On the basis of the above results, the plausible mechanism
was tested, these reactions furnished desired products in is depicted in Scheme 4. Firstly, the compound 6 was obtained
88–97% yield. When moderate electron withdrawing groups by two nucleophilic substitution reactions of enolized aromatic
such as chlorine and fluorine were introduced at the para-posi- ketone 1 and N,N-dimethylformamide dimethyl acetal 2 with
Table 3 Scope of aromatic ketones for one-pot synthesis of 1,5-benzodiazepinesa
a Reaction conditions: N,N-Dimethylformamide dimethyl acetal (1 mmol), aromatic ketones (1 mmol), 1,2-phenylenediamine compounds
(1 mmol), and aldehyde derivatives (1 mmol) in EtOH (2 ml), reflux to rt.
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Scheme 4 Plausible mechanism for the formation of 1,5-benzodiazepine 5.
the removal of the methanol molecules. Then, nucleophilic stituted 1,2-phenylenediamine is very strongly nucleophilic
substitution of the active amino group of substituted 1,2- (hard nucleophilic) compared to N2 (soft nucleophilic). The
phenylenediamine 3 onto the nitrogen atom of compound 6 N1 of substituted 1,2-phenylenediamine attacks the compound
leads to the formation of intermediate 7. This step has a very 6 to give the corresponding compound 7 via a nucleophilic
high selectivity. Subsequently, the other amino group of inter- substitution reaction. This result verifies the rationality of the
mediate 7 attacks the electrophilic carbonyl carbon of alde- mechanism proposed in this paper.
hyde derivatives 4 to give the corresponding intermediate 8 via
Furthermore, the compounds 7 obtained in this reaction
a nucleophilic addition–dehydration reaction. Adduct 8 under- and the corresponding isomers 10 were analyzed for zero-
goes intramolecular cyclization enabling the cyclic intermedi- point energy, thermodynamic energy, thermodynamic
ate 9, which suffers intramolecular proton transfer to give the enthalpy and Gibbs free energy (Table 5). Since the structures
product 5.
of products 7 are different from the structures of compounds
When the asymmetric 1,2-phenylenediamine compounds 10, the calculation of the respective energy parameters is also
were used as the substrate, selectivity of the position of R′ may different. The lower the energy, the more stable the structure.
exist. But only single isomers 7 were obtained in the experi- Considering that products 7ab–7ad were more stable than
ment. Previously, a similar structure of 1,5-benzodiazepines those of isomers 10ab–10ad, the selective formation of pre-
(Scheme 1A-II) was confirmed by X-ray diffraction.13 The result dominant products 7ab–7ad from the reaction of 3b–3d with
shows that the isomer formed is similar in both cases. To 6a is justified on thermodynamic grounds. This result also
further prove the structure of products 7, quantum chemical verifies the rationality of the mechanism proposed in this
calculations were performed and DFT studies based on the paper.
B3LYP method and 6-31G basis set were employed to carry out
the study.
To start with, NBO charge analysis of the substituted 1,2-
phenylenediamine 3b–3d was carried out to justify the selec-
Table 5 Zero-point energies, values of thermal energies, thermo-
tive attack at the nucleophilic centers (N1 and N2). The results
are summarized in Table 4. The NBO charge analysis reveals
that N1 and N2 are negatively charged. However, the charge
density of N1 is significantly higher than that of N2. N1 of sub-
dynamic enthalpy and Gibbs free energies of 7ab–7ad and 10ab–10ad
Table 4 Calculated NBO Charges of Optimized substituted 1,2-
phenylenediamine compounds 3b–3d
E≠/103
H≠/103
G≠/103
Comp.
Ezp/a.u.
kJ mol−1
kJ mol−1
kJ mol−1
7ab
10ab
7ac
10ac
7ad
10ad
−803.8051
−803.8046
−1224.1156
−1224.1149
−3335.6250
−3335.6245
−2110.3443
−2110.3427
−3213.8711
−3213.8694
−8757.6384
−8757.6371
−2110.3419
−2110.3402
−3113.8686
−3213.8669
−8757.6359
−8757.6346
−2110.5165
−2110.5166
−3214.0404
−3214.0384
−8757.8112
−8757.8104
N1
N2
−0.87425
−0.87029
−0.89655
−0.89506
−0.87002
−0.86700
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In summary, the structural assignment and computational added to the reaction mixture and stirred in refluxing ethanol.
results are in agreement with previous papers13,16 in which a The whole process takes 6 h. Finally, the aldehyde derivatives 4
similar reaction was performed.
(1 mmol) were added to the reaction mixture and stirred at
room temperature. Upon completion, as monitored by TLC,
the solid 5 was crystallised at 0 °C and the resulting solid was
washed with ethanol.
Conclusions
In conclusion, we have developed a catalyst-free and unpre-
cedented strategy for one-pot synthesis of diverse novel 3-acyl-
1,5-benzodiazepines, which provides a domino reaction of
N,N-dimethylformamide dimethyl acetal, aromatic ketones,
1,2-phenylenediamine and aldehyde derivatives. Moreover, the
reaction simultaneously installs one C–C bond, two C–N
bonds and one CvC bond to form one new seven-membered
ring, which resulted in the synthesis of highly functionalized
3-acyl-1,5-benzodiazepines containing carboxyl, ester and acyl
groups at the 2-position. The salient features of this method-
ology include the use of inexpensive and easily available start-
ing materials, convenient one-pot operation, ease of product
purification and good yields. Significantly, the protocol
showed a broad substrate scope and outstanding functional
group tolerance. The novel 1,5-benzodiazepines provide a col-
lection of promising compounds with structural diversity for
future bioassays and medical treatments.
3-Acyl-1,5-benzodiazepine 5aaa
Yellow solid; 245 mg, 84%; Mp: 188–189 °C; IR (KBr): 3330
(NH), 1704 (CvC), 1635 (CvO), 1540 (CvO) cm−1 1H NMR
;
(400 MHz, DMSO-d6, TMS): δ 2.14 (3H, s, Me), 5.24 (1H, d, J =
4.0 Hz, CH), 6.52 (1H, d, J = 4.0 Hz, NH), 6.71–6.88 (4H, m,
Ph), 7.10 (1H, d, J = 6.4 Hz, CH), 7.46 (5H, s, Ph), 9.52 (1H, d,
J = 6.4 Hz, NH); 13C NMR (100 MHz, DMSO-d6, TMS): δ 28.7,
63.0, 120.3, 120.6, 120.9, 123.9, 128.6, 130.2, 138.5, 140.7,
146.7, 192.9, 205.8; found C, 73.87; H, 5.36; N, 9.74%; M + 1
(mass spectrum), 293.2. C18H16N2O2 requires C, 73.95; H, 5.52;
N, 9.58%; M, 292.34.
3-Acyl-1,5-benzodiazepine 5aba
Pale yellow solid; 272 mg, 89%; Mp: 168–170 °C; IR (KBr): 3334
(NH), 1702 (CvC), 1635 (CvO), 1538 (CvO) cm−1 1H NMR
;
(400 MHz, DMSO-d6, TMS): δ 2.14 (3H, s, Me), 2.17 (3H, s, Me),
5.22 (1H, d, J = 2.4 Hz, CH), 6.44 (1H, d, J = 2.4 Hz, NH),
6.53–6.70 (3H, m, Ph), 7.08 (1H, d, J = 5.6 Hz, CH), 7.46 (5H, s,
Ph), 9.48 (1H, d, J = 6.0 Hz, NH); 13C NMR (100 MHz, DMSO-
d6, TMS): δ 20.8, 28.7, 62.8, 110.1, 120.5, 121.1, 127.7, 128.6,
130.1, 132.9, 138.3, 140.8, 146.6, 192.6, 205.8; found C, 74.38;
H, 5.69; N, 9.22%; M + 1 (mass spectrum), 307.2. C19H18N2O2
requires C, 74.49; H, 5.92; N, 9.14%; M, 306.37.
Experimental section
Materials and methods
Melting points were determined in open capillaries and were
uncorrected. The 1H NMR and 13C NMR spectral analyses were
performed on a 400 MHz (WIPM-NMR-400) nuclear magnetic
resonance spectrometer operating at 400/500 and 100/
125 MHz, respectively, in DMSO-d6 with the chemical shift
given in parts per million relative to tetramethylsilane (TMS)
as the internal standard. The signal multiplicities are rep-
resented by s (singlet), d (doublet), t (triplet), m (multiplet),
and q (quartet). The IR spectra were recorded on a Thermo
SCIENTIFIC IR spectrophotometer in KBr pellets and reported
in cm−1. The elemental analysis (C, H, N) was performed with
a VarioELIII Elemental Analyser. Low-resolution mass spectra
were recorded on a Thermo DSQ II mass spectrometer.
Synthetic grade chemicals were purchased from Aladdin and
were used as received. The solvents were commercial products
of analytical grade and dried according to the literature as
necessary. The reactions were monitored by thin-layer chrom-
atography (TLC) on pre-coated silica gel GF254 plates.
3-Acyl-1,5-benzodiazepine 5aca
Yellow solid; 264 mg, 81%; Mp: 186–188 °C; IR (KBr): 3340
(NH), 1702 (CvC), 1635 (CvO), 1527 (CvO) cm−1 1H NMR
;
(400 MHz, DMSO-d6, TMS): δ 2.16 (3H, s, Me), 5.29 (1H, d, J =
5.6 Hz, CH), 6.69 (1H, d, J = 5.6 Hz, NH), 6.73–6.92 (3H, m,
Ph), 7.09 (1H, d, J = 8.0 Hz, CH), 7.47 (5H, s, Ph), 9.64 (1H, d,
J = 8.0 Hz, NH); 13C NMR (100 MHz, DMSO-d6, TMS): δ 28.8,
62.6, 110.5, 119.5, 119.6, 121.8, 127.2, 128.5, 128.6, 128.9,
130.3, 140.0, 140.5, 146.2, 192.9, 205.6; found C, 66.24; H,
4.79; N, 8.46%; M + 1 (mass spectrum), 327.2. C18H15ClN2O2
requires C, 66.16; H, 4.63; N, 8.57%; M, 326.78.
3-Acyl-1,5-benzodiazepine 5ada
Light yellow solid; 293 mg, 79%; Mp: 181–183 °C; IR (KBr):
3337 (NH), 1700 (CvC), 1644 (CvO), 1528 (CvO) cm−1 1H
;
General methods
NMR (400 MHz, DMSO-d6, TMS): δ 2.19 (3H, s, Me), 5.31 (1H,
d, J = 5.6 Hz, CH), 6.76 (1H, d, J = 5.6 Hz, NH), 6.81–7.13 (3H,
Synthesis of 3-acyl-1,5-benzodiazepine derivatives 5.
Firstly, the reaction was carried out by taking a 1 : 1 mol m, Ph), 7.09 (1H, d, J = 7.6 Hz, CH), 7.50 (5H, s, Ph), 9.85 (1H,
ratio mixture of N,N-dimethylformamide 2 (1 mmol) and aro- d, J = 6.4 Hz, NH); 13C NMR (100 MHz, DMSO-d6, TMS): δ 28.8,
matic ketones 1 (1 mmol) in ethanol (2 mL) in a 50 mL round 62.5, 110.4, 115.1, 122.2, 122.2, 122.4, 128.5, 128.6, 129.4,
bottom flask with stirring at refluxing ethanol for 1 h, with 130.3, 140.4, 140.5, 146.2, 192.8, 205.7; found C, 58.31; H,
TLC showing the formation of
a
single product 6. 4.21; N, 7.41%; M + 1 (mass spectrum), 372.2. C18H15BrN2O2
Subsequently, the 1,2-phenylenediamine 3 (1 mmol) was requires C, 58.24; H, 4.07; N, 7.55%; M, 371.23.
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3-Acyl-1,5-benzodiazepine 5aea
J = 8.0 Hz, CH), 7.45–7.50 (5H, m, Ph), 9.57 (1H, d, J = 8.0 Hz,
NH), 12.38 (1H, s, COOH); 13C NMR (125 MHz, DMSO-d6,
TMS): δ 57.5, 111.6, 115.0, 122.0, 122.9, 123.2, 128.6, 128.6,
130.1, 130.3, 140.5, 140.6, 146.0, 172.6, 192.7; found C, 54.66;
Deep yellow solid; 299 mg, 93%; Mp: 179–180 °C; IR (KBr):
3334 (NH), 1696 (CvC), 1635 (CvO), 1527 (CvO) cm−1 1H
;
NMR 400 MHz, DMSO-d6, (TMS): δ 2.05 (3H, s, Me), 2.08 (3H,
s, Me), 2.12 (3H, s, Me), 5.18 (1H, d, J = 5.6 Hz, CH), 6.31 (1H,
d, J = 5.6 Hz, NH), 6.55–6.63 (2H, m, Ph), 7.06 (1H, d, J =
8.0 Hz, CH), 7.45 (5H, s, Ph), 9.38 (1H, d, J = 8.0 Hz, NH); 13C
NMR (100 MHz, DMSO-d6, TMS): δ 18.8, 19.2, 28.7, 63.0, 110.3,
121.4, 121.8, 127.8, 127.9, 128.5, 128.6, 130.0, 131.7, 135.9,
140.9, 146.7, 192.6, 205.8; found C, 74.89; H, 6.11; N, 8.88%;
M + 1 (mass spectrum), 321.2. C20H20N2O2 requires C, 74.98;
H, 6.29; N, 8.74%; M, 320.3.
H, 3.39; N, 7.65%;
M + 1 (mass spectrum), 373.1.
C17H13BrN2O3 requires C, 54.71; H, 3.51; N, 7.51%; M, 372.21.
3-Acyl-1,5-benzodiazepine 5aeb
Yellow solid; 306 mg, 95%; Mp: 191–193 °C; IR (KBr): 3357
(NH), 1749 (CvC), 1621 (CvO), 1502 (CvO) cm−1 1H NMR
;
(500 MHz, DMSO-d6, TMS): δ 2.06 (3H, s, Me), 2.08 (3H, s, Me),
5.11 (1H, d, J = 5.0 Hz, CH), 6.05 (1H, d, J = 5.5 Hz, NH),
6.57–6.65 (2H, m, Ph), 7.02 (1H, d, J = 8.5 Hz, CH), 7.42–7.48
(5H, m, Ph), 9.32 (1H, d, J = 8.5 Hz, NH), 12.12 (1H, s, COOH);
13C NMR (125 MHz, DMSO-d6, TMS): δ 18.9, 19.2, 57.8, 111.1,
121.3, 122.6, 128.2, 128.3, 128.5, 128.6, 130.0, 131.5, 136.5,
141.0, 146.7, 172.9, 192.6; found C, 70.68; H, 5.49; N, 8.73%;
M + 1 (mass spectrum), 323.3. C19H18N2O3 requires C, 70.79;
H, 5.63; N, 8.69%; M, 322.36.
3-Acyl-1,5-benzodiazepine 5aab
Yellow solid; 268 mg, 91%; Mp: 177–179 °C; IR (KBr): 3333
(NH), 1684 (CvC), 1639 (CvO), 1534 (CvO) cm−1 1H NMR
;
(500 MHz, DMSO-d6, TMS): δ 5.15 (1H, d, J = 5.0 Hz, CH), 6.32
(1H, d, J = 5.0 Hz, NH), 6.73–6.89 (4H, m, Ph), 7.05 (1H, d, J =
8.5 Hz, CH), 7.45–7.48 (5H, m, Ph), 9.47 (1H, d, J = 8.0 Hz,
NH), 12.23 (1H, s, COOH); 13C NMR (125 MHz, DMSO-d6,
TMS): δ 57.7, 111.4, 120.4, 120.6, 121.5, 123.7, 128.5, 128.6,
130.2, 130.7, 138.9, 140.8, 146.6, 172.9, 192.7; found C, 69.41;
H, 4.74; N, 9.49%; M + 1 (mass spectrum), 295.2. C17H14N2O3
requires C, 69.38; H, 4.79; N, 9.52%; M, 294.31.
3-Acyl-1,5-benzodiazepine 5aac
Pale yellow solid; 277 mg, 86%; Mp: 90–92 °C; IR (KBr): 3333
(NH), 1709 (CvC), 1637 (CvO), 1526 (CvO) cm−1 1H NMR
;
(500 MHz, DMSO-d6, TMS): δ 0.98 (3H, t, J = 7.0, Me), 3.93 (2H,
q, J = 6.5, CH2), 5.22 (1H, d, J = 5.5 Hz, CH), 6.43 (1H, d, J =
5.5 Hz, NH), 6.76–6.89 (4H, m, Ph), 7.09 (1H, d, J = 8.0 Hz,
CH), 7.46–7.46 (5H, m, Ph), 9.51 (1H, d, J = 8.0 Hz, NH); 13C
NMR (125 MHz, DMSO-d6, TMS): δ 14.6, 57.7, 60.6, 110.8,
120.4, 120.9, 121.5, 123.8, 128.5, 128.6, 130.2, 131.0, 138.5,
140.7, 146.7, 171.3, 192.5; found C, 70.83; H, 5.69; N, 8.61%;
M + 1 (mass spectrum), 323.2. C19H18N2O3 requires C, 70.79;
H, 5.63; N, 8.69%; M, 322.36.
3-Acyl-1,5-benzodiazepine 5abb
Pale yellow solid; 290 mg, 94%; Mp: 189–190 °C; IR (KBr): 3325
(NH), 1717 (CvC), 1637 (CvO), 1518 (CvO) cm−1 1H NMR
;
(500 MHz, DMSO-d6, TMS): δ 2.17 (3H, s, Me), 5.16 (1H, d, J =
4.0 Hz, CH), 6.25 (1H, d, J = 4.5 Hz, NH), 6.56–6.72 (3H, m,
Ph), 7.05 (1H, d, J = 8.5 Hz, CH), 7.45–7.48 (5H, m, Ph), 9.43
(1H, d, J = 8.5 Hz, NH), 12.22 (1H, s, COOH); 13C NMR
(125 MHz, DMSO-d6, TMS): δ 20.8, 57.6, 111.0, 120.4, 121.4, 3-Acyl-1,5-benzodiazepine 5abc
121.7, 128.3, 128.5, 128.6, 130.1, 132.7, 138.7, 140.9, 146.6,
Pale yellow solid; 302 mg, 90%; Mp: 94–96 °C; IR (KBr): 3333
(NH), 1717 (CvC), 1637 (CvO), 1541 (CvO) cm−1 1H NMR
172.9, 192.5; found C, 70.26; H, 5.32; N, 8.89%; M + 1 (mass
spectrum), 309.2. C18H16N2O3 requires C, 70.12; H, 5.23; N,
9.09%; M, 308.34.
;
(500 MHz, DMSO-d6, TMS): δ 1.00 (3H, t, J = 6.0, Me), 2.17 (3H,
s, Me), 3.94 (2H, q, J = 6.0, CH2), 5.21 (1H, d, J = 5.5 Hz, CH),
6.33 (1H, d, J = 6.0 Hz, NH), 6.58–6.74 (3H, m, Ph), 7.07 (1H, d,
J = 8.0 Hz, CH), 7.45–7.49 (5H, m, Ph), 9.46 (1H, d, J = 8.0 Hz,
NH); 13C NMR (125 MHz, DMSO-d6, TMS): δ 14.6, 20.8, 57.6,
60.5, 110.5, 120.4, 121.6, 121.7, 128.4, 128.5, 128.6, 130.1,
132.8, 138.3, 140.9, 146.6, 171.4, 192.3; found C, 71.53; H,
6.11; N, 8.17%; M + 1 (mass spectrum), 337.2. C20H20N2O3
requires C, 71.41; H, 5.99; N, 8.33%; M, 336.39.
3-Acyl-1,5-benzodiazepine 5acb
Purple solid; 292 mg, 89%; Mp: 204–206 °C; IR (KBr): 3318
(NH), 1709 (CvC), 1645 (CvO), 1534 (CvO) cm−1 1H NMR
;
(500 MHz, DMSO-d6, TMS): δ 5.16 (1H, d, J = 5.5 Hz, CH), 6.60
(1H, d, J = 5.5 Hz, NH), 6.77–6.93 (3H, m, Ph), 7.03 (1H, d, J =
8.0 Hz, CH), 7.45–7.49 (5H, m, Ph), 9.57 (1H, d, J = 8.0 Hz,
NH), 12.36 (1H, s, COOH); 13C NMR (125 MHz, DMSO-d6,
TMS): δ 57.4, 111.5, 120.0, 120.3, 121.7, 127.0, 128.6, 128.6,
129.7, 130.3, 140.3, 140.6, 146.0, 172.7, 192.7; found C, 62.25;
3-Acyl-1,5-benzodiazepine 5acc
Purple solid; 259 mg, 77%; Mp: 100–102 °C; IR (KBr): 3322
(NH), 1715 (CvC), 1640 (CvO), 1549 (CvO) cm−1 1H NMR
;
H, 4.11; N, 8.39%;
M + 1 (mass spectrum), 329.2.
C17H13ClN2O3 requires C, 62.11; H, 3.99; N, 8.52%; M, 328.75.
(500 MHz, DMSO-d6, TMS): δ 1.03 (3H, t, J = 6.5, Me), 3.99 (2H,
q, J = 6.5, CH2), 5.24 (1H, d, J = 5.0 Hz, CH), 6.69 (1H, d, J =
4.5 Hz, NH), 6.79–7.09 (3H, m, Ph), 6.95 (1H, d, J = 8.0 Hz,
3-Acyl-1,5-benzodiazepine 5adb
Yellow solid; 327 mg, 88%; Mp: 200–202 °C; IR (KBr): 3302 CH), 7.47 (5H, m, Ph), 9.62 (1H, d, J = 7.5 Hz, NH); 13C NMR
(NH), 1725 (CvC), 1645 (CvO), 1549 (CvO) cm−1 1H NMR (125 MHz, DMSO-d6, TMS): δ 14.6, 57.4, 60.8, 110.9, 120.3,
;
(500 MHz, DMSO-d6, TMS): δ 5.17 (1H, d, J = 5.5 Hz, CH), 6.60 120.4, 121.7, 127.1, 128.5, 128.6, 129.9, 130.3, 139.9, 140.5,
(1H, d, J = 5.5 Hz, NH), 6.76–7.06 (3H, m, Ph), 7.08 (1H, d, 146.1, 171.1, 192.5; found C, 63.82; H, 4.67; N, 7.99%; M + 1
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(mass spectrum), 357.2. C19H17ClN2O3 requires C, 63.96; H, 3-Acyl-1,5-benzodiazepine 5eaa
4.80; N 7.85%; M, 356.81.
Tangerine solid; 280 mg, 83%; Mp: 191–192 °C; IR (KBr): 3334
(NH), 1702 (CvC), 1635 (CvO), 1533 (CvO) cm−1 1H NMR
;
(400 MHz, DMSO-d6, TMS): δ 2.15 (3H, s, Me), 5.27 (1H, d, J =
4.8 Hz, CH), 6.59 (1H, d, J = 5.6 Hz, NH), 6.83–6.89 (4H, m,
Ph), 7.02 (1H, d, J = 8.0 Hz, CH), 7.71–8.31 (4H, m, Ph), 9.71
(1H, d, J = 8.4 Hz, NH); 13C NMR (100 MHz, DMSO-d6, TMS):
δ 28.6, 62.8, 110.5, 120.4, 120.8, 120.9, 123.9, 124.3, 129.7,
129.7, 138.6, 146.9, 147.4, 148.3, 190.6, 205.5; found C, 63.95;
H, 4.32; N, 12.56%; M + 1 (mass spectrum), 338.2. C18H15N3O4
requires C, 64.09; H, 4.48; N, 12.46%; M, 337.34.
3-Acyl-1,5-benzodiazepine 5adc
Yellow solid; 328 mg, 82%; Mp: 102–104 °C; IR (KBr): 3286
(NH), 1716 (CvC), 1637 (CvO), 1549 (CvO) cm−1 1H NMR
;
(500 MHz, DMSO-d6, TMS): δ 0.97 (3H, t, J = 6.5, Me), 3.93 (2H,
q, J = 6.5, CH2), 5.18 (1H, d, J = 5.0 Hz, CH), 6.63 (1H, d, J =
4.5 Hz, NH), 6.79–7.03 (3H, m, Ph), 6.89 (1H, d, J = 8.0 Hz,
CH), 7.41 (5H, m, Ph), 9.56 (1H, d, J = 7.0 Hz, NH); 13C NMR
(125 MHz, DMSO-d6, TMS): δ 14.6, 57.4, 60.8, 111.0, 115.1,
122.0, 123.2, 123.3, 128.5, 128.6, 130.3, 130.3, 140.2, 140.5,
146.1, 171.1, 192.5; found C, 56.76; H, 4.12; N, 7.11%; M + 1
(mass spectrum), 403.1. C19H17BrN2O3 requires C, 56.87; H,
4.27; N, 6.98%; M, 402.04.
3-Acyl-1,5-benzodiazepine 5bbb
Pale yellow solid; 312 mg, 97%; Mp: 200–202 °C; IR (KBr): 3357
(NH), 1709 (CvC), 1605 (CvO), 1573 (CvO) cm−1 1H NMR
;
(500 MHz, DMSO-d6, TMS): δ 2.18 (3H, s, Me), 2.37 (3H, s, Me),
5.14 (1H, d, J = 4.5 Hz, CH), 6.21 (1H, d, J = 4.5 Hz, NH),
6.56–6.73 (3H, m, Ph), 7.07 (1H, d, J = 8.0 Hz, CH), 7.26–7.38
3-Acyl-1,5-benzodiazepine 5baa
Pale yellow solid; 269 mg, 88%; Mp: 193–194 °C; IR (KBr): 3334 (4H, m, Ph), 9.38 (1H, d, J = 8.5 Hz, NH), 12.19 (1H, s, COOH);
(NH), 1702 (CvC), 1635 (CvO), 1533 (CvO) cm−1 1H NMR 13C NMR (125 MHz, DMSO-d6, TMS): δ 20.8, 21.4, 57.7, 110.9,
;
(400 MHz, DMSO-d6, TMS): δ 2.14 (3H, s, Me), 2.36 (3H, s, Me), 120.3, 121.3, 121.7, 128.3, 128.7, 129.1, 132.6, 138.0, 138.7,
5.22 (1H, d, J = 5.6 Hz, CH), 6.49 (1H, d, J = 5.6 Hz, NH), 139.9, 146.3, 172.9, 192.5; found C, 70.74; H, 5.59; N, 8.73%;
6.70–6.87 (4H, m, Ph), 7.11 (1H, d, J = 8.0 Hz, CH), 7.25–7.38 M + 1 (mass spectrum), 323.3. C19H18N2O3 requires C, 70.79;
(4H, m, Ph), 9.45 (1H, d, J = 8.0 Hz, NH); 13C NMR (100 MHz, H, 5.63, N, 8.69%; M, 322.36.
DMSO-d6, TMS): δ 21.4, 28.7, 63.1, 110.6, 120.3, 120.8, 123.8,
3-Acyl-1,5-benzodiazepine 5cbb
128.7, 129.1, 130.2, 137.8, 138.4, 139.9, 146.3, 192.8, 205.7;
found C, 74.63; H, 6.07; N, 9.01%; M + 1 (mass spectrum),
307.2. C19H18N2O2 requires C, 74.49; H, 5.92; N, 9.14%; M,
306.37.
Yellow solid; 300 mg, 92%; Mp: 196–198 °C; IR (KBr): 3357
(NH), 1717 (CvC), 1629 (CvO), 1597 (CvO) cm−1 1H NMR
;
(500 MHz, DMSO-d6, TMS): δ 2.18 (3H, s, Me), 5.15 (1H, d, J =
2.5 Hz, CH), 6.24 (1H, d, J = 1.5 Hz, NH), 6.57–6.75 (3H, m,
Ph), 7.05 (1H, d, J = 8.0 Hz, CH), 7.27–7.55 (4H, m, Ph), 9.46
(1H, d, J = 7.5 Hz, NH), 12.21 (1H, s, COOH); 13C NMR
(125 MHz, DMSO-d6, TMS): δ 20.8, 57.7, 110.9, 115.4, 115.6,
120.4, 121.4, 121.7, 128.3, 131.0, 131.1, 132.8, 138.7, 146.5,
172.9, 191.2; found C, 66.39; H, 4.77; N, 8.45%; M + 1 (mass
spectrum), 327.3. C19H18N2O3 requires C, 66.25; H, 4.63; N,
8.58%; M, 326.33.
3-Acyl-1,5-benzodiazepine 5caa
Pale yellow solid; 254 mg, 82%; Mp: 192–194 °C; IR (KBr): 3328
(NH), 1696 (CvC), 1642 (CvO), 1538 (CvO) cm−1 1H NMR
;
(400 MHz, DMSO-d6, TMS): δ 2.14 (3H, s, Me), 5.23 (1H, d, J =
5.6 Hz, CH), 6.52 (1H, d, J = 5.2, NH), 6.73–6.86 (4H, m, Ph),
7.09 (1H, d, J = 8.4 Hz, CH), 7.26–7.54 (4H, m, Ph), 9.54 (1H, d,
J = 8.0 Hz, NH); 13C NMR (100 MHz, DMSO-d6, TMS): δ 28.6,
63.1, 110.5, 115.4, 115.6, 120.2, 120.6, 120.9, 123.9, 130.1,
131.0, 131.1, 137.1, 137.1, 138.4, 146.6, 162.1, 164.5, 191.6,
205.7; found C, 69.80; H, 4.92; N, 8.88%; M + 1 (mass spec-
trum), 311.2. C18H15FN2O2 requires C, 69.67; H, 4.87; N,
9.03%; M, 310.33.
3-Acyl-1,5-benzodiazepine 5dbb
Yellow solid; 311 mg, 91%; Mp: 190–192 °C; IR (KBr): 3341
(NH), 1693 (CvC), 1629 (CvO), 1534 (CvO) cm−1 1H NMR
;
(500 MHz, DMSO-d6, TMS): δ 2.18 (3H, s, Me), 5.13 (1H, d, J =
5.0 Hz, CH), 6.24 (1H, d, J = 5.5 Hz, NH), 6.56–6.74 (3H, m,
Ph), 7.02 (1H, d, J = 8.5 Hz, CH), 7.46–7.53 (4H, m, Ph), 9.46
(1H, d, J = 8.0 Hz, NH), 12.18 (1H, s, COOH); 13C NMR
(125 MHz, DMSO-d6, TMS): δ 20.8, 57.6, 111.0, 120.5, 121.4,
121.7, 128.2, 128.6, 130.4, 132.9, 134.8, 138.7, 139.6, 146.6,
172.8, 191.1; found C, 63.11; H, 4.49; N, 8.09%; M + 1 (mass
spectrum), 343.2. C18H15ClN2O3 requires C, 63.07; H, 4.41; N,
8.17%; M, 342.78.
3-Acyl-1,5-benzodiazepine 5daa
Yellow solid; 251 mg, 77%; Mp: 195–196 °C; IR (KBr): 3340
(NH), 1702 (CvC), 1635 (CvO), 1533 (CvO) cm−1 1H NMR
;
(400 MHz, DMSO-d6, TMS): δ 2.14 (3H, s, Me), 5.22 (1H, d, J =
5.6 Hz, CH), 6.54 (1H, d, J = 6.0 Hz, NH), 6.71–6.88 (4H, m,
Ph), 7.07 (1H, d, J = 8.0 Hz, CH), 7.48–7.54 (4H, m, Ph), 9.57
(1H, d, J = 8.0 Hz, NH); 13C NMR (100 MHz, DMSO-d6, TMS):
δ 28.6, 63.0, 110.59, 120.3, 120.6, 120.9, 124.0, 128.7, 130.0,
3-Acyl-1,5-benzodiazepine 5ebb
130.5, 134.9, 138.4, 139.4, 146.7, 191.6, 205.6; found C, 66.33; Red solid; 335 mg, 95%; Mp: 196–198 °C; IR (KBr): 3349 (NH),
H, 4.87; N, 8.46%;
(mass spectrum), 327.2. 1693 (CvC), 1645 (CvO), 1541 (CvO) cm−1 1H NMR
(500 MHz, DMSO-d6, TMS): δ 2.18 (3H, s, Me), 5.18 (1H, d,
M
+
1
;
C18H15ClN2O2 requires C, 66.16; H, 4.63; N, 8.57%; M, 326.78.
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J = 5.0 Hz, CH), 6.30 (1H, d, J = 5.5 Hz, NH), 6.58–6.76 (3H, m, NH); 13C NMR (125 MHz, DMSO-d6, TMS): δ 14.6, 57.7, 60.5,
Ph), 6.97 (1H, d, J = 8.5 Hz, CH), 7.68–8.31 (4H, m, Ph), 9.59 109.9, 120.5, 120.9, 121.3, 123.9, 124.0, 125.1, 131.0, 137.7,
(1H, d, J = 8.5 Hz, NH), 12.24 (1H, s, COOH); 13C NMR 138.6, 148.1, 148.2, 158.1, 171.3, 188.5; found C, 66.79; H,
(125 MHz, DMSO-d6, TMS): δ 20.8, 57.4, 111.1, 120.7, 121.5, 5.16; N, 13.23%; M + 1 (mass spectrum), 323.9. C18H17N3O3
121.8, 123.9, 128.0, 129.7, 133.2, 138.9, 147.2, 147.3, 148.3, requires C, 66.86; H, 5.30; N, 13.00%; M, 323.35.
172.7, 190.1; found C, 61.21; H, 4.37; N, 11.81%; M + 1 (mass
spectrum), 354.3. C18H15N3O5 requires C, 61.19; H, 4.28; N,
11.89%; M, 353.33.
Conflicts of interest
3-Acyl-1,5-benzodiazepine 5fab
There are no conflicts to declare.
Deep yellow solid; 286 mg, 95%; Mp: 118–120 °C; IR (KBr):
3302 (NH), 1684 (CvC), 1629 (CvO), 1534 (CvO) cm−1 1H
;
NMR (500 MHz, DMSO-d6, TMS): δ 5.21 (1H, d, J = 3.5 Hz, CH),
6.42 (1H, d, J = 6.0 Hz, NH), 6.77–6.93 (4H, m, Ph), 8.00–8.03 Acknowledgements
(2H, m, thiazole ring), 9.19 (1H, d, J = 6.5 Hz, CH), 10.12 (1H,
We are grateful for financial support from the National Natural
d, J = 8.5 Hz, NH), 12.24 (1H, s, COOH); 13C NMR (125 MHz,
DMSO-d6, TMS): δ 57.9, 109.8, 120.7, 120.8, 121.4, 124.4, 125.6,
130.5, 139.2, 144.2, 148.2, 171.0, 172.7, 177.0; found C, 55.71;
Science Foundation of China (21776060 and 21276064)
and the Natural Science Foundation of Hebei Province
(B2016205165).
H, 3.53; N, 14.10%;
M − 1 (mass spectrum), 300.1.
C14H11N3O3S requires C, 55.80; H, 3.68; N, 13.95%; M, 301.32.
3-Acyl-1,5-benzodiazepine 5gab
Notes and references
Brown solid; 274 mg, 93%; Mp: 200–202 °C; IR (KBr): 3357
(NH), 1701 (CvC), 1629 (CvO), 1581 (CvO) cm−1
;
1H NMR
1 G. Wess, M. Urmann and B. Sikenberger, Angew. Chem.,
2001, 113, 3443, (Angew. Chem., Int. Ed., 2001, 40, 3341).
2 G. Grossi, M. Di Braccio, G. Roma, V. Ballabeni,
M. Tognolini, F. Calcina and E. Barocelli, Eur. J. Med.
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3 A. Maleki and M. Kamalzare, Catal. Commun., 2014, 53, 67.
4 Y. Y. Shen, J. Han and X. C. Sun, Tetrahedron, 2015, 71,
4053.
5 M. Di Braccio, G. Grossi, G. Roma, L. Vargiu, M. Mura and
M. E. Marongiu, Eur. J. Med. Chem., 2001, 36, 935.
6 R. Kaoua, B. Nedjar-Kolli, T. Roisnel, Y. L. Gal and D. Lorcy,
Tetrahedron, 2013, 69, 4636.
7 G. Saini, P. Kumar, G. S. Kumar, A. R. K. Mangadan and
M. Kapur, Org. Lett., 2018, 20, 441.
(500 MHz, DMSO-d6, TMS): δ 5.22 (1H, d, J = 2.0 Hz, CH), 6.35
(1H, d, J = 2.5 Hz, NH), 6.74–7.66 (5H, m, pyridine ring), 7.79
(1H, d, J = 8.0 Hz, CH), 7.91–8.61 (4H, m, Ph), 9.68 (1H, d, J =
8.0 Hz, NH), 12.20 (1H, s, COOH); 13C NMR (125 MHz, DMSO-d6,
TMS): δ 57.6, 110.6, 120.5, 120.6, 121.4, 123.9, 124.0, 125.1,
130.7, 137.7, 139.0, 148.0, 148.2, 158.3, 172.9, 188.7; found C,
65.22; H, 4.61; N, 14.01%; M + 1 (mass spectrum), 295.9.
C16H13N3O3 requires C, 65.08; H, 4.44; N, 14.23%; M, 295.30.
3-Acyl-1,5-benzodiazepine 5fac
Yellow solid; 303 mg, 92%; Mp: 164–166 °C; IR (KBr): 3318
(NH), 1709 (CvC), 1629 (CvO), 1522 (CvO) cm−1
;
1H NMR
(500 MHz, DMSO-d6, TMS): δ 0.94 (3H, t, J = 7.0, Me), 3.90 (2H,
q, J = 2.5, CH2), 5.25 (1H, d, J = 4.5 Hz, CH), 6.53 (1H, d, J =
6.0 Hz, NH), 6.95–8.04 (6H, m, Ph), 8.01–8.04 (2H, m, thiazole
ring), 9.23 (1H, d, J = 7.0 Hz, CH), 10.18 (1H, d, J = 8.5 Hz,
NH); 13C NMR (125 MHz, DMSO-d6, TMS): δ 14.5, 57.9, 60.6,
8 Y. Segawa, T. Maekawa and K. Itami, Angew. Chem., Int. Ed.,
2015, 54, 66.
9 B. Jiang, C. Li, F. Shi, S.-J. Tu, K. Parminder, W. Walter and
G. Li, J. Org. Chem., 2010, 75, 2962.
109.1, 120.9, 121.0, 121.3, 124.5, 125.7, 130.8, 138.8, 144.2, 10 L. Z. Wang, X. Q. Li and Y. S. An, Org. Biomol. Chem., 2015,
148.4, 170.8, 171.1, 177.0; found C, 58.27; H, 4.41; N, 12.85%; 13, 5497.
M + 1 (mass spectrum), 330.2. C16H15N3O3S requires C, 58.34; 11 Y. Y. Wu, K. Q. Tian, T. Yang, X. Q. Du and P. Zhang,
H, 4.59; N, 12.76%; M, 329.37.
Chin. J. Org. Chem., 2013, 33, 1465.
12 Y. J. Jiang, J. J. Cai, J. P. Zou and W. Zhang, Tetrahedron
Lett., 2010, 51, 471.
3-Acyl-1,5-benzodiazepine 5gac
Pale gray solid; 287 mg, 89%; Mp: 164–166 °C; IR (KBr): 3318 13 L. Y. Yin and L. Z. Wang, Tetrahedron Lett., 2016, 57, 5935.
(NH), 1717 (CvC), 1645 (CvO), 1526 (CvO) cm−1 1H NMR 14 C. J. Menet, S. R. Fletcher and G. Van Lommen, J. Med.
(500 MHz, DMSO-d6, TMS): δ 0.96 (3H, t, J = 7.0, Me), 3.91 (2H, Chem., 2014, 57, 9323.
q, J = 5.5, CH2), 5.23 (1H, d, J = 5.5 Hz, CH), 6.44 (1H, d, J = 15 A. Z. A. Hassanien, S. A. S. Ghozlan and M. H. Elnagdi,
5.5 Hz, NH), 6.76–7.66 (5H, m, pyridine ring), 7.83 (1H, d, J = J. Heterocycl. Chem., 2003, 40, 225.
8.5 Hz, CH), 7.92–8.61 (4H, m, Ph), 9.72 (1H, d, J = 8.5 Hz, 16 Y. W. Sun and L. Z. Wang, New J. Chem., 2018, 42, 20032.
;
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