Regioselective syntheses of 3-hydroxy-4-aryl-3,4,5-trihydro-2H-benzo[b][1,4]diazepin-2(1H)-ones and 3-benzylquinoxalin-2(1H)-ones from arylglycidates when exposed to 1,2-diaminobenzenes

Article abstract of DOI:10.1016/j.tet.2020.131478

Representatives of two pharmacologically significant classes of compounds – 3-hydroxy-4-aryl-3,4,5-trihydro-2H-benzo[b][1,4]diazepin-2(1H)-ones and 3-benzylquinoxalin-2(1H)-ones – obtained in reactions of 1,2-diaminobenzenes with methyl 3-arylglycidates in boiling acetic acid. Substituents in arylglycidates determine the direction of processes. Electron withdrawing substituents (NO₂), halogen atoms (Cl, Br, F), as well as the absence of substituents, provide the formation of benzo[b][1,4]diazepin-2(1H)-one derivatives, and electron donating groups (OMe, Me) contribute to the formation of 3-benzylquinoxalin-2(1H)-ones. As a result, a new rare representatives of 3-hydroxy-4-aryl-3,4,5-trihydro-2H-benzo[b][1,4]diazepin-2(1H)-ones were obtained and a new method for producing 3-benzylquinoxalin-2(1H)-ones has been proposed.

Full text of DOI:10.1016/j.tet.2020.131478

Tetrahedron 76 (2020) 131478
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Regioselective syntheses of 3-hydroxy-4-aryl-3,4,5-trihydro-2H-
benzo[b][1,4]diazepin-2(1H)-ones and 3-benzylquinoxalin-2(1H)-
ones from arylglycidates when exposed to 1,2-diaminobenzenes
Vakhid A. Mamedov*, Vera L. Mamedova, Victor V. Syakaev, Julia K. Voronina,
Essam M. Mahrous, Dmitry E. Korshin, Shamil K. Latypov, Oleg G. Sinyashin
Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, 420088, Kazan, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Representatives of two pharmacologically significant classes of compounds e 3-hydroxy-4-aryl-3,4,5-
trihydro-2H-benzo[b][1,4]diazepin-2(1H)-ones and 3-benzylquinoxalin-2(1H)-ones e obtained in re-
actions of 1,2-diaminobenzenes with methyl 3-arylglycidates in boiling acetic acid. Substituents in
arylglycidates determine the direction of processes. Electron withdrawing substituents (NO2), halogen
atoms (Cl, Br, F), as well as the absence of substituents, provide the formation of benzo[b][1,4]diazepin-
2(1H)-one derivatives, and electron donating groups (OMe, Me) contribute to the formation of 3-
Received 6 June 2020
Received in revised form
17 July 2020
Accepted 4 August 2020
Available online 24 August 2020
benzylquinoxalin-2(1H)-ones. As
trihydro-2H-benzo[b][1,4]diazepin-2(1H)-ones were obtained and a new method for producing 3-
benzylquinoxalin-2(1H)-ones has been proposed.
a result, a new rare representatives of 3-hydroxy-4-aryl-3,4,5-
Keywords:
Regioselective syntheses
3-Hydroxy-4-aryl-3,4,5-trihydro-2H-benzo
[b][1,4]diazepin-2(1H)-ones
Diastereoselectivity
© 2020 Elsevier Ltd. All rights reserved.
3-Benzylquinoxalin-2(1H)-ones
Methyl 3-arylglycidates
1. Introduction
undergo further transformations in this system and lead to com-
pounds 4, 5, and 6, respectively. The alternative pathway to prod-
Epoxides are a very reactive class of compounds with great
synthetic potential [1]. The considerable ring strain present in ep-
oxides and the polarity of asymmetrically substituted epoxides
makes them versatile starting materials for regioselective ring
opening under the influence of nucleophilic reagents [1aef].
Rearrangement processes are of great importance in the chemistry
of epoxides, in particular, Meinwald rearrangement [1i,2], leading
to the formation of carbonyl compounds, which, due to their ac-
tivity, open a chain of new transformations. In this paper, the re-
actions of methyl 3-arylglycidates 1 with 1,2-diaminobenzenes 2 in
an acidic medium are investigated. An acidic environment favors
Meinwald rearrangement [3], leading to the formation of 3-
arylpyruvates 3 (path a, Schema 1a), while 1,2-diaminobenzenes
are capable of nucleophilic opening of the epoxy ring [1f, 4] with
the formation of intermediate structures A or B depending on the
site of initial attack by the amino group of the epoxy ring in the aryl
glycidate (paths b and c, Schema 1). Products 3, A, and B can
ucts 5 and 6 is possible via the initial amidation of arylglycidates
[4aec] to intermediate compounds C and D, followed by intra-
molecular nucleophilic opening of the epoxy ring and 6-exo-tet or
7-exo-tet closure [5] (path d, Scheme 1).
The place of the initial attack in the reactions of opening the
epoxy ring by nucleophiles depends on the workload of the carbon
atoms of the epoxy ring, on the type of substituents on the epoxy
ring, on the medium in which the reaction is carried out (neutral,
basic or acidic) [6]. Despite the large amount of the accumulated
material in this field of knowledge often proves difficult to predict
the site of nucleophilic attack for epoxides that are vicinally
disubstituted with various functional groups, all the more compli-
cated to predict the final product of the reaction when the nucle-
ophile itself is bifunctional. Usually, the epoxy ring under acidic
conditions opens on the side of that carbon atom, the positive
charge on which is more delocalized when the CeO bond is broken
[6b]. In reactions of 3-arylglycidates 1 with 1,2-diaminobenzenes 2
in boiling AcOH, depending on where the epoxy ring opens, it was
possible to expect the formation of 3-(
a-hydroxybenzyl)-3,4-
* Corresponding author.
E-mail address: mamedov@iopc.ru (V.A. Mamedov).
dihydroquinoxalin-2(1H)-ones and 3-hydroxy-4-aryl-3,4,5-
5
https://doi.org/10.1016/j.tet.2020.131478
0040-4020/© 2020 Elsevier Ltd. All rights reserved.

2
V.A. Mamedov et al. / Tetrahedron 76 (2020) 131478
Scheme 1. Possible ways to open the epoxy ring and further transformations.
trihydro-2H-benzo[b][1,4]diazepin-2(1H)-ones 6 via 6-exo-trig and
7-exo-trig closure [5] of intermediate compounds A and B (paths b
and c, Scheme 1) or via 6-exo-tet and 7-exo-tet cyclization of D (path
d, Schema 1). Although the reaction of ethyl 3-phenylgycidate with
1,2-diaminobenzenes in boiling xylene for 48 h is known, leading to
3-hydroxy-4-phenyl-3,4,5-trihydro-2H-benzo[b][1,4]diazepin-
2(1H)-one [4l], and the reaction of methyl 3-(4-methoxyphenyl)
glycidate with 2-nitroaniline is known [4k], leading to B, this does
not guarantee that the reactions will go in the same direction with
other 3-arylglycidates in another medium.
monitored by TLC. As can be seen from Table 1, the reaction time
depends on the nature of the substituents in the aromatic aldehyde.
In the cases of aromatic aldehydes with electron donating sub-
stituents (entries 6, 7, Table 1), the time to complete the reactions is
2e5 times longer than in the cases of using other aromatic alde-
hydes (entries 1e5, Table 1). The reactions proceed with the for-
mation of mixtures cis and trans isomers in the cases of 1a-d, f with
the predominance of trans isomer in the mixtures, and with the
formation only trans isomer in the cases of 1e, g. The assignment of
signals in 1H NMR spectra of arylglycidates 1 to cis and trans iso-
mers was made on the basis of literature data [8], according to
which the coupling constants, JHH, between the protons of the
epoxy ring in trans isomers is less (3JHH ¼ 2e4 Hz) than in cis
2. Results and discussion
(3JHH ¼ 4e6 Hz). Analysis
оf
1H NMR spectra of crude products 1
The 3-arylglycidates 1 used for the investigation was obtained
under Darzens condensation conditions. The procedure of the
Darzens condensation is the same as that described for N,3-
diaryloxirane-2-carboxamides [7], except that only methyl chlor-
oacetate instead of chloroacetamides with variously substituted
aromatic aldehydes were used and the reactions were carried out in
THF in the presence of t-BuOK at 0 оС at the beginning of the
process (0.5 h) and at room temperature until its completion
shows that cis isomer is in two diastereomeric forms, and the
predominant trans isomer is in one. The products isolated during
the treatment of reaction mixtures with water in solid form (1e, g)
or in the form of oils (1a-d, f), were used for further trans-
formations without additional purification.
The solid compounds 6 or 4 were isolated from the reactions of
arylglycidates 1 with 1,2-diaminobenzenes 2 in AcOH after treat-
ment with water and subsequent treatment of the thick masses
with acetone. The choice between compounds 5 and 6 in favor of 6
was made by single-crystal X-ray analysis of one of the products,
namely 6h (entry 8, Table 2; Fig. 1). Investigated crystal is the
racemic form of the diastereomer with the same configuration of
chiral centers C3 and C4 (RR, SS). It crystallizes with two enantio-
meric molecules in an independent part of the unit cell. Both
molecules have the same conformation with minor difference in
the position of the 4-chlorophenyl substituent. The bond lengths,
valence and torsion angles have values that are within standard for
each type of chemical bond. An interesting feature of the molecular
structure of this compound is the intramolecular hydrogen bond
O11eH11/O10. Тhe main supramolecular synthon is a centro-
symmetric H-dimer formed by two crystallographically indepen-
dent enantiomeric molecules bonded by NeH/O interactions
(Fig. 2; Table 3).
Table 1
Synthesis of 3-arylglycidates.
Entry
Ar
Product
Time, h
Yield,a
%
1
3
2
4
5
6
7
Ph
1a
1b
1c
1d
1e
1f
52
24
24
36
24
96
120
97 (1:0.3)
99 (1:0.3)
97 (1:0.6)
96 (1:0.3)
98 (1:0)b
97 (1:0.15)
79 (1:0)b
4-BrC6H4
4-ClC6H4
2-FC6H4
4-NO2C6H4
4-MeC6H4
4-MeOC6H4
A similar trihydrobenzodiazepinone structure was assigned to
6a-s according to NMR spectroscopic data (see SI).
In the cases of unsymmetrically substituted 1,2-
diaminobenzenes 2e, f, regioisomers 6 and 6′ with the location of
1g
a
The brackets indicate a ratio of trans:cis isomers, determined by 1H NMR.
trans-Isomer precipated as the residue during the treatment of reaction mix-
b
tures with water.

V.A. Mamedov et al. / Tetrahedron 76 (2020) 131478
3
Table 2
the R substituent in the eighth or seventh positions of the trihy-
drobenzodiazepinone system, respectively may be formed in re-
actions with arylglycitates 1 (Scheme 2). The mixtures of the
regioisomers 6 and 6′ with predominance 6 were received in re-
actions of 4-chloro-1,2-diaminobenzene 2e with arylglycidates 1c
and 1e (entries 11, 19, Table 2). The ratio of regioisomers was
determined from NMR spectra, and their identification was made
from HMBC (15Ne1H) experiments on H9eN1 cross-peaks for 6 and
H6eN5 for 6′. Only one regioisomer 6′l was obtained in reaction of
4-nitro-1,2-diaminobenzene 2f with arylglycidate 1c (entry 12,
Table 2). This result allowed us to make a choice between paths с
and d, leading to 6′l and 6l in favor of c (Scheme 3). The regiose-
lectivity can be explained by the stronger deactivating effect of the
electron withdrawing NO2 group on the NH2 group in the para-
position of 2f that leads to the attack by another amino group of
the C2 electrophilic center in 1c.
Benzodiazepine derivatives, in particular benzo[b][1,4]dia-
zepines are compounds widely used in medicine [9]. They are
commonly used as anxiolytic and anticonvulsive drugs [9b]. Clo-
zapine, which is an atypical antipsychotic medication and used to
treat schizophrenia, is the derivative of benzo[b][1,4]diazepine.
Clozapine derivatives, in turn, are promising in the treatment of
Hantington and Parkinson diseases [9c]. The proposed facile, effi-
cient synthesis for a wide range of 3-hydroxy-4-aryl-3,4,5-trihydro-
2H-benzo[b][1,4]diazepin-2(1H)-ones may be in demand in the
search for new drugs.
When 3-arylglycidates with an electron donating group in the
aryl fragment were used in reactions with 1,2-diaminobenzenes in
boiling AcOH, 3-benzylquinoxalin-2(1H)-ones 4 were obtained
(entries 20e24, Table 2). Only in one case (entry 2, Table 2) after
treating the reaction mass with acetone, we observed in the 1H
NMR spectrum the presence of products 6b and 4b with a ratio of
1:1; the product 6b was isolated from the mixture in pure form by a
column chromatography.
Despite the great importance of this class of compounds as
potential biological agents and building blocks for the synthesis of
various quinoxaline derivatives [10], a relatively small number of
methods for their synthesis are known. All of them at the initial or
final stage include condensation of 1,2-diaminobenzenes with
dicarbonyl compounds, such as arylpyruvic acids [9] (method a,
Scheme 4) or its derivatives [10,12,13] (methods b-d, Scheme 4).
Arylpyruvic acids, in turn, are obtained by acid hydrolysis either
1,3-oxazolidin-4-ones [14], prepared from amides 3-arylglycidic
acid [15], or 4-arylidene-2-methyloxazol-5-ones, prepared by
condensation of aromatic aldehydes with N-acetylglycine in acetic
anhydride [16]. Quinoxalinones 4 were obtained in a tandem pro-
cess involving directly 4-arylidene-2-methyloxazol-5-ones in
condensation with 1,2-diaminobenzene (method b, Scheme 4) [12].
The condensation 1,2-diaminobenzenes with 3-cyano- [13] and 3-
Synthesis of 3-hydroxy-4-aryl-3,4,5-trihydro-2H-benzo[b][1,4]diazepin-2(1H)-ones
6 and 3-benzylquinoxalin-2(1H)-ones 4.
Entry
2
R
1
Ar
Product
Yield,a
65
%
6
4
1
2
3
4
5
6
7
8
2a 4,5-H,H
2b 4,5-Me,Me 1a Ph
1a Ph
6a
6b
6c
6d
6e
6f
6g
6h
4b 82% (1:1)b, 31%
2c 4,5-Cl,Cl
2a 4,5-H,H
2c 4,5-Cl,Cl
2d 4,5-F,F
2a 4,5-H,H
1a Ph
72
75
63
52
63
68
73
56
1b 4-BrC6H4
1b 4-BrC6H4
1b 4-BrC6H4
1c 4-ClC6H4
2b 4,5-Me,Me 1c 4-ClC6H4
9
2c 4,5-Cl,Cl
2d 4,5-F,F
2e 4-Cl
2f 4-NO2
2b 4,5-Me,Me 1d 2-FC6H4
2c 4,5-Cl,Cl
2a 4,5-H,H
2b 4,5-Me,Me 1e 4-NO2C6H4
2c 4,5-Cl,Cl
2d 4,5-F,F
2e 4-Cl
2a 4,5-H,H
2b 4,5-Me,Me 1f 4-MeC6H4
2d 4,5-F,F
2a 4,5-H,H
2c 4,5-Cl,Cl
1c 4-ClC6H4
1c 4-ClC6H4
1c 4-ClC6H4
1c 4-ClC6H4
6i
6j
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
6k þ 6′k
68 (4:1)c
61
49
58
73
78
6′l
6m
6n
6o
6p
6q
6r
6s þ 6′s
1d 2-FC6H4
1e 4-NO2C6H4
1e 4-NO2C6H4
1e 4-NO2C6H4
1e 4-NO2C6H4
1f 4-MeC6H4
80
79
73 (2:1)c
4t
4u 61
4y 43
4w 58
4x 65
52
1f 4-MeC6H4
1g 4-MeOC6H4
1g 4-MeOC6H4
a
Yields refer to isolated products.
Yields of the mixture products 6b and 4b (brackets indicate a ratio of 6b:4b) and
b
pure product 6b after column chromatography, respectively.
c
The brackets indicate a ratio of the regioisomers 6:6′, estimated by the NMR
spectra.
chloro-3-arylpyruvates [10] leads to 3-(a-cyano)- and 3-(a-
chloro)benzylquinoxalin-2-ones, respectively, which were con-
verted to 4 by some manipulations [10,13] (methods c, d, Schemes
4). In our method, 3-benzylquinoxalin-2(1H)-ones 4t-x are formed
in
a
tandem process from 1,2-diaminobenzenes and 3-
arylglycidates with the electron donating groups in the aryl frag-
ment (method e, Scheme 4). The first stage of the process is
probably Meinwald rearrangement, the second stage is condensa-
tion of arylpyruvate with 1,2-diaminobenzene (path a, Scheme 1).
To confirm the formation of 3-benzylquinoxalinones 4 via aryl-
pyruvates 3, a control experiment was carried out on the example
of 3-(4-methoxyphenyl)glycidate (1g), which was involved in the
synthesis of 3-(4-methoxyphenyl)pyruvic acid (3g) (Scheme 5). The
latter was turned into benzylquinoxalinone 4w (entry 23, Table 2)
by reaction with 1,2-diaminobenzene (2a). A notable feature of
arylpyruvic acid is their tautomerism [17]. It should be pointed out
Fig. 1. The molecular structure of benzo[b][1,4]diazepin-2(1H)-one 6h shown using
molecule A as an example. Ellipsoids are shown with 50% probability.

4
V.A. Mamedov et al. / Tetrahedron 76 (2020) 131478
Fig. 2. H-bonds in crystal of benzo[b][1,4]diazepin-2(1H)one 6h.
formation of 3-hydroxy-4-aryl-3,4,5-trihydro-2H-benzo[b][1,4]
Table 3
H-bonds in crystal of benzo[b][1,4]diazepin-2(1H)one 6h.
diazepin-2(1H)-ones by sequential opening of the epoxy ring and
7-exo-trig closing or, in the case of electron donating substituents,
to 3-benzylquinoxalin-2(1H)-ones via Meinwald rearrangement
and сondensation. Studies on the search for more applications of 3-
arylglycidates as coupling partners in synthesis of heterocycles are
currently under way in our laboratory.
H-Bond
D - H
H$$$A
D$$$A
D - H$$$A
N1A-H1A$$$O10B
N1BeH1B/O10A
N5A-H5A$$$O10A
N5BeH5B/O11B
O11A-H11A … O10A
O11BeH11B/O10B
C4A-H4AA$$$N5A
0.90
0.90
0.90
0.90
0.95
0.95
1.00
2.01
1.92
2.56
2.25
1.97
2.05
2.60
2.909 (3)
2.818 (3)
3.006 (4)
3.154 (3)
2.626 (3)
2.597 (3)
3.474 (5)
180
180
111
180
125
115
145
4. Experimental section
4.1. General methods
Melting points were determined on a hot-stage apparatus.
Infrared (IR) spectra were recorded on an FT-IR spectrometer. Nu-
clear magnetic resonance (NMR) spectra were recorded on Brucer
spectrometer Avance III-500 (500 and 400 MHz for 1H, 126 MHz for
13C, and 51 MHz for 15N) in DMSO‑d6 at 303 K. The spectrometer
was equipped with a pulsed gradient unit capable of producing
magnetic field pulse gradients in the z-direction of 53.5 G cmꢀ1. All
the spectra were obtained in a 5-mm gradient broad band probe-
Scheme 2. Monosubstituted 1,2-diaminobenzenes in the reactions with 3-
arylglycidates.
that in the 1H NMR spectrum in DMSO‑d6, only 2-hydroxy-3-(4-
methoxy)acrylic acid (3′g) is detected (Scheme 5).
head. Chemical shifts are reported on the d (ppm) scale and referred
to the solvent DMSO‑d6 (2.49 ppm for 1H and 39.5 ppm for 13C
NMR) and to external MeCN (235.5 for 15N NMR).
3. Conclusion
4.2. Typical procedure for Darzens condensation
In summary, we demonstrated that in system 3-arylglycidate e
1,2-diaminobenzene e AcOH, depending on the substituent in the
aryl fragment of glycidate, two processes occur that lead to the
Powdered t-BuOK (7.86 g, 0.07 mol) was added in three portions
to the stirring solution of methyl chloroacetate (7.60 g, 0.07 mol)

V.A. Mamedov et al. / Tetrahedron 76 (2020) 131478
5
Scheme 3. Possible pathways of the reaction of 2f with 1c.
Scheme 4. Synthetic routes to 3-benzylquinoxalin-2-ones.
and aromatic aldehyde (0.07 mol) in THF (30 mL) at 0e5 ꢁC. The
4.2.2. Methyl 3-(4-bromophenyl)glycidate (1b)
stirring continued for 0.5 h at 0e5 ꢁC and for 24e120 h at room
temperature. After completion of the process, monitored by TLC the
reaction mixture was quenched with ice water (100 mL). The
products 1a-d, f were separated as the oils, 1e, g as the solids and
were used in further syntheses without additional purification.
4.2.1. Methyl 3-phenylglycidate (1a)
Yield: 17.82 g (99%), yellow oil; 1H NMR (500 MHz, DMSO‑d6) for
trans-1b:
d
3.75 (3H s, OMe), 3.81 (1H, d, J ¼ 1.7 Hz, H2), 4.20 (1H, d,
J ¼ 1.7 Hz, H3), 7.33 (2H, d, J ¼ 8.4 Hz, H2-Ar, H6-Ar), 7.57 (2H, d,
J ¼ 8.4 Hz, H3-Ar, H5-Ar); 1H NMR (500 MHz, DMSO‑d6) for cis-1b:
d
3.50 (3H, s, OMe), 4,07 (1H, d, J ¼ 4.7 Hz, H2), 4.41 (1H, d,
Yield: 12.10 g (97%), colorless oil; 1H NMR (400 MHz, DMSO‑d6)
J ¼ 4.7 Hz, H3), 7.33 (2H, d, J ¼ 8.5 Hz, H2-Ar, H6-Ar), 7.54 (2H, d,
for trans-1a:
d
3.75 (3H, s, OMe), 3.81 (1H, d, J ¼ 1.8 Hz, H2), 4.19
J ¼ 8.5 Hz, H3-Ar, H5-Ar); 13C{1H} NMR (126 MHz, DMSO‑d6) for
(1H, d, J ¼ 1.8 Hz, H3), 7.28e7.45 (5H, m, Ph); 1H NMR (400 MHz,
trans-1b: d 168.4 (C8),135.0 (C1),131.9 (C2, C6),128.9 (C3, C5),122.6
DMSO‑d6) for cis-1a:
d
3.49 (3H, s, OMe), 4.07 (1H, d, J ¼ 4.8 Hz, H2),
(C4), 56.9 (C6), 55.2 (C7), 52.8 (C9); 13C{1H} NMR (126 MHz,
DMSO‑d6) for cis-1b: 167.0 (C8), 133.2 (C1), 131.4 (C3, C5), 129.1
(C2, C6), 122.1 (C4), 56.6 (C6), 56.1 (C7), 52.3 (C9); anal. calcd for
10H19BrO3: C, 46.72; H, 3.53; Br, 31.08. Found: C, 46.67; H, 3.66; Br,
30.89.
4.40 (1H, d, J ¼ 4.8 Hz, H3), 7.35e7.50 (5H, m, Ph); NMR (400 MHz,
d
DMSO‑d6) for cis′-1a:
d
3.63 (3H, s, OMe), 4.82 (1H, d, J ¼ 5.5 Hz,
H2), 5.12 (1H, d, J ¼ 5.5 Hz, H3), 7.30e7.50 (5H, m, Ph); anal. calcd
C
for C10H10O3: C, 67.41; H, 5.66. Found: C, 67.47; H, 5.69.

6
V.A. Mamedov et al. / Tetrahedron 76 (2020) 131478
Scheme 5. The synthesis of 3-(4-methoxybenzyl)quinoxalin-2(1H)-one from 3-(4-methoxyphenyl)glycidate via 3-(4-methoxyphenyl)pyruvic acid.
4.2.3. Methyl 3-(4-chlorophenyl)glycidate (1c)
for trans-1f:
7.19 (2H, d, J ¼ 7.9 Hz, H3-Ar, H5-Ar), 7.26 (2H, d, J ¼ 7.9 Hz, H2-Ar,
H6-Ar); 1H NMR (400 MHz, DMSO‑d6) for cis-1f:
3.50 (3H, s, OMe),
d 3.75 (3H, s, OMe), 3.79 (1H, s, H2), 4.13 (1H, s, H3),
d
4.04 (1H, d, J ¼ 4.7 Hz, H2), 4.34 (1H, d, J ¼ 4.7 Hz, H3), 7.15 (2H, d,
J ¼ 7.8 Hz, H3-Ar, H5-Ar), 7.26 (2H, d, J ¼ 7.8 Hz, H2-Ar, H6-Ar); anal.
calcd for C11H12O3: C, 68.74; H, 6.29. Found: C, 68.82; H, 6.23.
Yield: 14.43 g (97%), colorless oil; 1H NMR (400 MHz, DMSO‑d6)
4.2.7. Methyl trans-3-(4-methoxyphenyl)glycidate (1g)
for trans-1c:
d
3.75 (3H, s, OMe), 3.83 (1H, d, J ¼ 1.6 Hz, H2), 4.21
(1H, d, J ¼ 1.6 Hz, H3), 7.40e7.43 (4H, m, Ar); 1H NMR (400 MHz,
DMSO‑d6) for cis-1c:
d
3.50 (3H, s, OMe), 4.07 (1H, d, J ¼ 4.7 Hz, H2),
4.42 (1H, d, J ¼ 4.7 Hz, H3), 7.37e7.47 (4H, m, Ar); NMR (400 MHz,
DMSO‑d6) for cis′-1c:
3.66 (3H, s, OMe), 4.87 (1H, d, J ¼ 5.0 Hz, H2),
5.15 (1H, d, J ¼ 5.0 Hz, H3), 7.40e7.45 (4H, m, Ar); anal. calcd for
10H9ClO3: C, 56.49; H, 4.27; Cl, 16.67. Found: C, 56.53; H, 4.36; Cl,
d
C
Yield: 11.52 g (79%), white solid, mp 70e71 ꢁC; IR (KBr):
1517, 1252, 1929 cmꢀ1; 1H NMR (400 MHz, DMSO‑d6):
3.74 (3H, s,
n 1732,
16.53.
d
OMe1), 3.76 (3H, s, OMe-Ar), 3.81 (1H, br s, H2), 4.10 (1H, br s, H3),
6.94 (2H, d, J ¼ 7.0 Hz, H3-Ar, H5-Ar), 7.30 (2H, d, J ¼ 7.0 Hz, H2-Ar,
H6-Ar); anal. calcd for C11H12O4: C, 63.45; H, 5.81. Found: C, 63.58;
H, 5.89.
4.2.4. Methyl 3-(2-fluorophenyl)glycidate (1d)
4.3. Transformation of 3-(4-methoxyphenyl)glycidate (1g) to 2-
hydroxy-3-(4-methoxy)acrylic acid (30g)
A solution of 3-(4-methoxyphenyl)glycidate (0.10 g, 0.48 mmol)
in acetic acid (5 mL) was refluxed for 3 h. The reaction mixture was
cooled and was quenched with water (5 mL). The precipitate was
filtered off and washed with small portion of ether to afford an
analytically pure product of 3′g.
Yield: 13.18 g (96%), colorless oil; 1H NMR (400 MHz, DMSO‑d6)
for trans-1d:
d
3.77 (3H, s, OMe), 3.86 (1H, d, J ¼ 1.7 Hz, H2), 4.32
(1H, d, J ¼ 1.7 Hz, H3), 7.19e7.31 (4H, m, Ar); 1H NMR (400 MHz,
DMSO‑d6) for cis-1d:
d
3.49 (3H, s, OMe), 4.12 (1H, d, J ¼ 4.6 Hz, H2),
4.51 (1H, d, J ¼ 4.6 Hz, H3), 7.38e7.45 (4H, m, Ar); NMR (400 MHz,
DMSO‑d6) for cis′-1d:
3.69 (3H, s, OMe), 4.87 (1H, d, J ¼ 4.7 Hz,
H2), 5.15 (1H, d, J ¼ 4.7 Hz, H3), 7.38e7.45 (4H, m, Ar); anal. calcd for
10H9FO3: C, 61.22; H, 4.62; F, 9.68. Found: C, 61.51; H, 4.32; F, 9.53.
d
C
4.2.5. Methyl trans-3-(4-nitrophenyl)glycidate (1e)
Yield: 0.09 g (96%), yellow solid, mp 232 ꢁC (190 ꢁC [18]; 194 ꢁC
[19]); IR (KBr):
DMSO‑d6): 3.81 (3H, s, OMe), 6.51 (1H, s, H3), 7.02 (2H, d,
n ;
3100, 1734, 1600, 1269 cmꢀ1 1H NMR (400 MHz,
d
J ¼ 8.8 Hz, H3-Ar, H5-Ar), 7.69 (2H, d, J ¼ 8.8 Hz, H2-Ar, H6-Ar); anal.
calcd for C10H10O4: C, 61.85; H, 5.19. Found: C, 61.78; H, 5.18.
Yield: 15.31 g (98%), yellow solid, mp 143 ꢁC; IR (KBr):
n 1750,
4.4. Typical procedure for the synthesis of 3-hydroxy-4-aryl-3,4,5-
trihydro-2H-benzo[b][1,4]diazepin-2(1H)-ones and 3-
benzylquinoxalin-2(1H)-ones
1518, 1349, 1215; 1H NMR (400 MHz, DMSO‑d6):
d 3.76 (3H, s, OMe),
3.89 (1H, d, J ¼ 1.8 Hz, H2), 4.39 (1H, d, J ¼ 1.8 Hz, H3), 7.64 (2H, d,
J ¼ 8.8 Hz, H2-Ar, H6-Ar); 8.23 (2H, d, J ¼ 8.8 Hz, H3-Ar, H5-Ar);
anal. calcd for C10H9NO5: C, 53.82; H, 4.06; N, 6.28. Found: C, 53.73;
H, 4.09; N, 6.31.
A mixture of the corresponding 3-arylglycidate (0.01 mol) and
1,2-diaminobenzene (0.01 mol) in AcOH (7 mL) was refluxed for
6 h. After cooling to room temperature, the reaction mixture was
poured into 7% water solution NaHCO3 (150 mL). The resulting
precipitate or thick oil were filtered off and washed with water
(2 ꢂ 10 mL) or decanted by water (2 ꢂ 100 mL) and dried in air, then
processed by acetone (3 mL for the precipitates and 7 mL for oils).
The resulting new precipitations has been filtered and dried in the
air to yield the pure samples of 6a, c-j,m-r, 6′l, 6a, c-f and the
mixtures 6k and 6′k (4:1), 6s and 6’s (2:1), 6b and 4b (1:1). The
product 6b was isolated in pure form by column chromatography
4.2.6. Methyl 3-(4-tolyl)glycidate (1f)
Yield: 13.05 g (97%), colorless oil; 1H NMR (400 MHz, DMSO‑d6)

V.A. Mamedov et al. / Tetrahedron 76 (2020) 131478
7
(hexane/ethylacetate ¼ 50/1).
232e234 ꢁC4l); IR (KBr):
n
3316, 3177, 3056, 2919, 1677, 1480,
1451 cmꢀ1; 1H NMR (500 MHz, DMSO‑d6):
d
4.24 (1H, d, J ¼ 8.1 Hz,
4.4.1. 3-Hydroxy-4-pheyl-3,4,5-trihydro-2H-benzo[b][1,4]diazepin-
2(1H)-ones (6a)
H3-Bd), 4.57 (1H, d, J ¼ 8.1 Hz, H4-Bd), 6.10 (1H, br s, NH5-Bd), 7.10
(1H, s, H8-Bd), 7.12 (1H, s, H5-Bd), 7.27 (1H, dd, J ¼ 7.9, 7.9 Hz, H4-
Ar), 7.33 (2H, d, J ¼ 7.8 Hz, H2-Ar, H6-Ar), 7.34 (2H, dd, J ¼ 7.9, 7.8 Hz,
H3-Ar, H5-Ar), 9.98 (s, 1H, NH1-Bd); 13C{1H} NMR (126 MHz,
DMSO‑d6): d 171.8 (C2-Bd), 142.5 (C1-Ar), 139.9 (C5a-Bd), 129.1 (C7-
Bd), 128.1 (C3-Ar, C5-Ar), 127.3 (C4-Ar), 127.1 (C2-Ar, C6-Ar), 126.9
(C8-Bd), 125.6 (C8a-Bd), 122.3 (C9-Bd), 120.2 (C5-Bd), 72.9 (C3-Bd),
67.1 (C4-Bd); 15N NMR (51 MHz, DMSO‑d6):
d 129.0 (N1-Bd), 70.6
(N5-Bd); anal. calcd for C15H12Cl2N2O2: C, 55.75; H, 3.74; Cl, 21.94;
N, 8.67. Found: C, 55.68; H, 3.62; N, 8.61.
Yield: 1.65 g (65%), white powder, mp 165e166 ꢁC (mp
4.4.4. 3-Hydroxy-4-(4-bromophenyl)-3,4,5-trihydro-2H-benzo[b]
[1,4]diazepin-2(1H)-one (6d)
166e168 ꢁC4l); IR (KBr):
n ;
3429, 3318, 3194, 3056, 1682 cmꢀ1 1H
NMR (500 MHz, DMSO‑d6):
d
4.12 (1H, d, J ¼ 9.0 Hz, H3-Bd), 4.45
(1H, d, J ¼ 9.0 Hz, H4-Bd), 4.89 (1H, br s, OH), 5.52 (1H, s, NH5- Bd),
6.83 (1H, ddd, J ¼ 7.4, 7.4, 1.7 Hz, H7-Bd), 6.91e6.97 (3H, m, H5-Bd,
H6-Bd, H8-Bd), 7.25e7.40 (5H, Ar), 9.88 (1H, s, NH1-Bd); 13C{1H}
NMR (126 MHz, DMSO‑d6):
d 172.2 (C2-Bd), 143.9 (C1-Ar), 139.4
(C5a-Bd), 128.0 (C3-Ar, C5-Ar), 128.0 (C4-Ar), 127.2 (C8a-Bd), 127.1
(C3-Ar, C5-Ar), 124.9 (C7-Bd), 121.9 (C9-Bd), 121.1 (C5-Bd), 120.2
(C8-Bd), 71.1 (C3-Bd), 68.9 (C4-Bd); 15N NMR (51 MHz, DMSO‑d6):
d
130.1 (N1-Bd), 69.1 (N5-Bd); anal. calcd for C15H14N2O2: C, 70.85;
H, 5.55; N, 11.02. Found: C, 70.61; H, 5.59; N, 11.10.
Yield: 2.50 g (75%), tan powder, mp 199e200 ꢁC; IR (KBr):
3353, 3176, 3060, 2930, 1693 cmꢀ1
n
;
d
4.12 (1H, d, J ¼ 9.1 Hz, H4-Bd),
4.4.2. 3-Hydroxy-4-phenyl-7,8-dimethyl-3,4,5-trihydro-2H-benzo
[b][1,4]diazepin-2(1H)-one (6b)
4.47 (1H, d, J ¼ 9.1 Hz, H3-Bd), 4.98 (1H, s, OH), 5.58 (1H, s, NH5-Bd),
6.84 (1H, ddd, J ¼ 7.7, 7.1, 1.4 Hz, H7-Bd), 6.15e6.98 (3H, m, H5-Bd,
H6-Bd, H8-Bd), 7.27 (2H, d, J ¼ 8.4 Hz, H2-Ar, H6-Ar), 7.53 (2H, d,
J ¼ 8.4 Hz, H3-Ar, H5-Ar), 9.91 (1H, s, NH1-Bd); 13C{1H} NMR
(126 MHz, DMSO‑d6): d 172.5 (C2-Bd),143.6 (C1-Ar),139.6 (C5a-Bd),
131.4 (C2-Ar, C6-Ar), 129.8 (C3-Ar, C5-Ar), 128.4 (C8a-Bd), 125.4
(C7-Bd), 122.4 (C9-Bd), 121.4 (C5-Bd), 120.8 (C8-Bd), 120.7 (C4-Ar),
72.1 (C3-Bd), 68.5 (C4-Bd); 15N NMR (51 MHz, DMSO‑d6):
d 129.4
(N1-Bd), 68.4 (N5-Bd); anal. calcd for C15H13BrN2O2: C, 54.07; H,
3.93; Br, 23.98; N, 8.41. Found: C, 54.25; H, 3.69; Br, 23.73; N, 8.62.
Yield: 0.87 g (31%), yellow powder, mp 185e187 ꢁC (mp
184e186 ꢁC4l); IR (KBr):
n ;
3375, 3185, 3064, 2916, 1669 cmꢀ1 1H
4.4.5. 3-Hydroxy-4-(4-bromophenyl)-7,8-dichloro-3,4,5-trihydro-
2H-benzo[b][1,4]diazepin-2(1H)-one (6e)
NMR (500 MHz, DMSO‑d6): d 2.11 (3H, s, Me8-Bd), 2.12 (3H, s, Me7-
Bd), 4.08 (1H, dd, J ¼ 9.3 Hz, 6.6 Hz, H3-Bd), 4.38 (1H, d, J ¼ 9.3 Hz,
H4-Bd), 4.77 (1H, d, J ¼ 6.6 Hz, OH), 5.21 (1H, s, NH5-Bd), 6.70 (1H, s,
H5-Bd), 6.72 (1H, s, H8-Bd), 7.27 (1H, dd, J ¼ 7.3, 7.3 Hz, H4-Ar), 7.29
(2H, d, J ¼ 7.4 Hz, H2-Ar, H6-Ar), 7.30 (2H, dd, J ¼ 7.4, 7.3 Hz, H3-Ar,
H5-Ar), 9.76 (1H, s, NH1-Bd); 13C{1H} NMR (126 MHz, DMSO‑d6):
d
172.3 (C2-Bd), 144.2 (C1-Ar), 136.9 (C5a-Bd), 132.6 (C7-Bd), 128.1
(C8-Bd), 128.0 (C3-Ar, C5-Ar), 127.1 (C2-Ar, C4-Ar, C6-Ar), 125.8
(C8a-Bd), 122.8 (C9-Bd), 122.3 (C5-Bd), 71.4 (C3-Bd), 69.4 (C4-Bd),
18.9 (Me7-Bd), 18.5 (Me8-Bd); 15N NMR (51 MHz, DMSO‑d6):
d
128.7 (N1-Bd), 66.8 (N5-Bd); anal. calcd for C17H18N2O2: C, 72.32;
H, 6.43; N, 9.92. Found: C, 72.60; H, 6.51; N, 10.06.
Yield: 2.53 g (63%), tan powder, mp 233e234 ꢁC; IR (KBr):
3350, 3181, 3066, 2924, 1677, 1488 cmꢀ1 1H NMR (500 MHz,
DMSO‑d6):
n
4.4.3. 3-Hydroxy-4-phenyl-7,8-dichloro-3,4,5-trihydro-2H-benzo
[b][1,4]diazepin-2(1H)-one (6c)
;
d
4.22 (1H, d, J ¼ 8.1 Hz, H3-Bd), 4.58 (1H, d, J ¼ 8.1 Hz,
H4-Bd), 6.12 (br s, 1H, NH5-Bd), 7.10 (2H, s, H5-Bd, H8-Bd), 7.28 (2H,
d, J ¼ 8.3 Hz, H2-Ar, H6-Ar), 7.54 (2H, d, J ¼ 8.3 Hz, H3-Ar, H5-Ar),
9.98 (s, 1H, NH1-Bd); 13C{1H} NMR (126 MHz, DMSO‑d6):
d 171.7
(C2-Bd), 141.8 (C1-Ar), 139.8 (C5a-Bd), 131.0 (C3-Ar, C5-Ar), 129.4
(C2-Ar, C6-Ar), 127.1 (C8a-Bd), 125.7 (C7-Bd), 122.4 (C9-Bd), 120.5
(C4-Ar), 120.2 (C5-Bd), 119.9 (C8-Bd), 72.8 (C3-Bd), 66.3 (C4-Bd);
anal. calcd for C15H11BrCl2N2O2: C, 44.81; H, 2.76; Br, 19.87; Cl, 17.64
(Br þ Cl, 37.51); N, 6.97. Found: C, 44.65; H, 2.65; Br þ Cl, 37.71; N,
6.71.
Yield: 2.33
g
(72%), tan powder, mp 228e229 ꢁC (mp

8
V.A. Mamedov et al. / Tetrahedron 76 (2020) 131478
4.4.6. 3-Hydroxy-4-(4-bromophenyl)-7,8-difluoro-3,4,5-trihydro-
2H-benzo[b][1,4]diazepin-2(1H)-one (6f)
(2H, d, J ¼ 8.5 Hz, H2-Ar, H6-Ar), 7.37 (2H, d, J ¼ 8.5 Hz, H3-Ar), 9.76
(1H, s, NH1-Bd); 13C{1H} NMR (126 MHz, DMSO‑d6):
172.1 (C2-
d
Bd), 143.1 (C1-Ar), 136.7 (C5a-Bd), 132.7 (C7-Bd), 131.7 (C4-Ar),
128.9 (C2-Ar, C6-Ar), 128.3 (C8-Bd), 127.9 (C3-Ar, C5-Ar), 125.9
(C8a-Bd), 122.9 (C9-Bd), 122.3 (C5-Bd), 71.3 (C3-Bd), 68.5 (C4-Bd),
19.0 (Me7-Bd),18.5 (Me8-Bd); 15N NMR (51 MHz, DMSO‑d6):
d 127.5
(N1-Bd), 66.4 (N5-Bd); anal. calcd for C17H17ClN2O2: C, 64.46; H,
5.41; Cl, 11.19; N, 8.84. Found: C, 64.51; H, 4.49; Cl, 11.23; N, 8.73.
4.4.9. 3-Hydroxy-4-(4-chlorophenyl)-7,8-dichloro-3,4,5-trihydro-
2H-benzo[b][1,4]diazepin-2(1H)-one (6i)
Yield: 1.92 g (52%), violet power, mp 183e185 ꢁC; IR (KBr):
n
3372, 3050, 2926, 2853, 1688, 1530 cmꢀ1 1H NMR (500 MHz,
;
DMSO‑d6):
d
4.15 (1H, d, J ¼ 8.7 Hz, H3-Bd), 4.48 (1H, d, J ¼ 8.7 Hz,
H4-Bd), 5.71 (1H, br s, NH5-Bd), 6.89 (dd, 1H, J ¼ 12.3, 8.1 Hz, H5-
Bd), 6.95 (1H, dd, J ¼ 12.1, 8.8 Hz, H8-Bd), 7.25 (2H, d, J ¼ 8.4 Hz,
H2-Ar, H6-Ar), 7.52 (2H, d, J ¼ 8.4 Hz, H3-Ar, H5-Ar), 9.89 (s, 1H,
NH1-Bd); anal. calcd for C15H11BrF2N2O2: C, 48.80; H, 3.00; Br,
21.64; F, 10.29 (Br þ F, 31.93); N, 7.59. Found: C, 48.69; H, 2.93;
Br þ F, 31.72; N, 7.63.
4.4.7. 3-Hydroxy-4-(4-chlorophenyl)-3,4,5-trihydro-2H-benzo[b]
[1,4]diazepin-2(1H)-one (6g)
Yield: 2.61 g (73%), white powder, mp 246e247 ꢁC; IR (KBr):
3358, 3193, 3073, 2934, 1691 cmꢀ1; 1H NMR (500 MHz, DMSO‑d6):
n
d
4.22 (1H, d, J ¼ 8.0 Hz, H3-Bd), 4.59 (1H, d, J ¼ 8.0 Hz, H4-Bd), 6.13
(1H, s, NH5-Bd), 7.09 (1H, s, H8-Bd), 7.10 (1H, s, H5-Bd), 7.34 (2H, d,
J ¼ 8.1 Hz, H2-Ar, H6-Ar), 7.40 (2H, d, J ¼ 8.1 Hz, H3-Ar, H5-Ar), 9.97
(1H, s, NH1-Bd); 13C{1H} NMR (126 MHz, DMSO‑d6):
d 171.6 (C2-
Bd), 141.4 (C1-Ar), 139.7 (C5a-Bd), 131.9 (C4-Ar), 129.0 (C2-Ar, C6-
Ar), 128.0 (C3-Ar, C5-Ar), 127.0 (C8a-Bd), 125.6 (C7-Bd), 122.4 (C9-
Bd), 120.1 (C5-Bd), 119.8 (C8-Bd), 72.8 (C3-Bd), 66.1 (C4-Bd); anal.
calcd for C15H11Cl3N2O2: C, 50.38; H, 3.10; Cl, 29.74; N, 7.83. Found:
C, 50.46; H, 3.22; Cl, 29.57; N, 8.01.
Yield: 1.82 g (63%), tan powder, mp 197e199 ꢁC; IR (KBr):
3176, 3061, 2930, 1694 cmꢀ1; 1H NMR (500 MHz, DMSO‑d6):
n
3355,
4.12
d
(1H, d, J ¼ 9.1 Hz, H3-Bd), 4.48 (1H, d, J ¼ 9.1 Hz, H4-Bd), 4.97 (1H, br
s, OH), 5.57 (1H, s, NH5-Bd), 6.83 (1H, ddd, J ¼ 7.4, 7.4, 1.5 Hz, H7-
Bd), 6.93 (1H, dd, J ¼ 7.8, 1.5 Hz, H5-Bd), 6.95 (1H, dd, J ¼ 7.4,
1.4 Hz, H8-Bd), 6.97 (1H, ddd, J ¼ 7.8, 7.4, 1.4 Hz, H6-Bd), 7.31 (2H, d,
J ¼ 8.5 Hz, H2-Ar, H6-Ar), 7.38 (2H, d, J ¼ 8.5 Hz, H3-Ar, H5-Ar), 9.89
4.4.10. 3-Hydroxy-4-(4-chlorophenyl)-7,8-difluoro-3,4,5-trihydro-
2H-benzo[b][1,4]diazepin-2(1H)-one (6j)
(1H, s, NH1-Bd); 13C{1H} NMR (126 MHz, DMSO‑d6):
d 172.0 (C2-
Bd), 142.8 (C1-Ar), 139.1 (C5a-Bd), 131.7 (C4-Ar), 129.0 (C2-Ar, C6-
Ar), 128.0 (C3-Ar, C5-Ar, C8a-Bd), 124.9 (C7-Bd), 121.9 (C9-Bd),
121.0 (C5-Bd), 120.3 (C8-Bd), 71.6 (C3-Bd), 68.0 (C4-Bd); 15N NMR
(51 MHz, DMSO‑d6):
d 129.4 (N1-Bd), 68.4 (N5-Bd); anal. calcd for
C
15H13ClN2O2: C, 62.40; H, 4.54; Cl, 12.28; N, 9.70. Found: C, 62.53;
H, 4.50; Cl, 11.99; N, 9.64.
4.4.8. 3-Hydroxy-4-(4-chlorophenyl)-7,8-dimethyl-3,4,5-trihydro-
2H-benzo[b][1,4]diazepin-2(1H)-one (6h)
Yield: 1.82 g (56%), brown powder, mp 238e240 ꢁC; IR (KBr):
3370, 3182, 3095, 3943, 1697, 1531 cmꢀ1 1H NMR (500 MHz,
DMSO‑d6):
n
;
d
4.17 (1H, d, J ¼ 8.7 Hz, H3-Bd), 4.51 (1H, d, J ¼ 8.7 Hz,
H4-Bd), 5.73 (1H, br s, NH5-Bd), 6.91 (1H, dd, J ¼ 12.2, 4.1 Hz, H5-
Bd), 6.96 (1H, dd, J ¼ 11.5, 3.2 Hz, H8-Bd), 7.33 (2H, d, J ¼ 8.4 Hz, H2-
Ar, H6-Ar), 7.40 (2H, d, J ¼ 8.4 Hz, H3-Ar, H5-Ar), 9.91 (s, 1H, NH1-
Bd); 13C{1H} NMR (126 MHz, DMSO‑d6):
d 172.0 (C2-Bd), 145.5 (dd,
J(CF) ¼ 350.5 Hz, J(CF) ¼ 13.3 Hz, C8-Bd), 143.7 (dd, J(CF) ¼ 346.3 Hz,
J(CF) ¼ 13.1 Hz, C7-Bd), 142.0 (C1-Ar), 136.3 (d, J(CF) ¼ 6.7 Hz, C5a-
Bd), 132.0 (C4-Ar), 129.0 (C2-Ar, C6-Ar), 128.1 (C3-Ar, C5-Ar), 124.4
(d, J(CF) ¼ 6.0 Hz, C8a-Bd), 110.2 (d, J(CF) ¼ 19.8 Hz, C9-Bd), 108.5 (d,
J(CF) ¼ 19.1 Hz, C5-Bd), 71.9 (C3-Bd), 67.9 (C4-Bd); 15N NMR
Yield: 2.15 g (68%), tan powder, mp 217e218 ꢁC; IR (KBr):
3183, 3069, 2919, 1670 cmꢀ1; 1H NMR (500 MHz, DMSO‑d6):
(3H, s, Me7-Bd), 2.11 (3H, s, Me8-Bd), 4.05 (1H, dd, J ¼ 9.2, 6.0 Hz,
H3-Bd), 4.40 (1H, d, J ¼ 9.2 Hz, H4-Bd), 4.86 (1H, d, J ¼ 6.0 Hz, OH),
5.25 (1H, s, NH5-Bd), 6.69 (1H, s, H5-Bd), 6.71 (1H, s, H8-Bd), 7.29
n
3361,
2.11
d
(51 MHz, DMSO‑d6): d 127.9 (N1-Bd), 68.0 (N5-Bd); anal. calcd for
C15H11ClF2N2O2: C, 55.48; H, 3.41; Cl, 10.92; F, 11.70 (Cl þ F, 22.62);
N, 8.63. Found: C, 55.39; H, 3.35; Cl þ F, 22.51; N, 8.57.

V.A. Mamedov et al. / Tetrahedron 76 (2020) 131478
9
4.4.11. 3-Hydroxy-4-(4-chlorophenyl)-8-chloro-3,4,5-trihydro-2H-
12.59. Found: C, 53.81; H, 3.69; Cl, 10.73; N, 12.64.
benzo[b][1,4]diazepin-2(1H)-one (6k) and 3-hydroxy-4-(4-
chlorophenyl)-7-chloro-3,4,5-trihydro-2H-benzo[b][1,4]diazepin-
2(1H)-one (60k)
4.4.13. 3-Hydroxy-4-(2-fluorophenyl)-7,8-dimethyl-3,4,5-trihydro-
2H-benzo[b][1,4]diazepin-2(1H)-one (6m)
Yield: 2.19 g (68%); 1H NMR (500 MHz, DMSO‑d6) for 6k:
d 4.16
(1H, d, J ¼ 8.6 Hz, H3-Bd), 4.53 (1H, d, J ¼ 8.6 Hz, H4-Bd), 5.73 (1H,
br s, NH5-Bd), 6.87 (d, J ¼ 8.3 Hz, H5-Bd), 6.97 (1H, c, H8-Bd), 6.98
(1H, d, J ¼ 8.3 Hz, H6-Bd), 7.32 (2H, d, J ¼ 8.3 Hz, H2-Ar, H5-Ar), 7.39
(2H, d, J ¼ 8.3 Hz, H3-Ar, H5-Ar), 9.94 (1H, s, NH1-Bd); 1H NMR
Yield: 1.47 g (49%), mp 257e258 ꢁC; IR (KBr):
2918, 1678 cmꢀ1; 1H NMR (500 MHz, DMSO‑d6):
n
3375, 3195, 3073,
2.10 (3H, s, Me7-
d
Bd), 2.11 (3H, s, Me8-Bd), 4.22 (1H, d, J ¼ 9.2 Hz, H3-Bd), 4.74 (1H, d,
J ¼ 9.2 Hz, H4-Bd), 4.87 (1H, br s, OH), 5.28 (1H, s, NH5-Bd), 6.65 (s,
1H, H5-Bd), 6.71 (1H, s, H8-Bd), 7.15 (1H, d, J ¼ 7.0 Hz, H6-Ar), 7.17
(1H, dd, J ¼ 7.1, 7.0 Hz, H5-Ar), 7.31 (1H, dd, J ¼ 13.1, 7.0 Hz, H3-Ar),
7.36 (1H, dd, J ¼ 7.1, 7.0 Hz, H4-Ar), 9.80 (1H, s, NH1-Bd); 13C{1H}
(500 MHz, DMSO‑d6) for 6′k:
d
4.17 (1H, d, J ¼ 8.8 Hz, H3-Bd), 4.54
(1H, d, J ¼ 8.8 Hz, H4-Bd), 5.87 (1H, br s, NH5-Bd), 6.80 (1H, d,
J ¼ 8.3 Hz, H7-Bd), 6.92 (1H, dd, J ¼ 8.3 Hz, H8-Bd), 6.97 (1H, c, H5-
Bd), 7.33 (2H, d, J ¼ 8.6 Hz, H2-Ar, H6-Ar), 7.40 (2H, d, J ¼ 8.6 Hz, H3-
Ar, H5-Ar), 9.92 (s, 1H, NH1-Bd); 13C{1H} NMR (126 MHz, DMSO‑d6)
NMR (126 MHz, DMSO‑d6):
d
172.0 (C2-Bd), 159.8 (d,
J(CF) ¼ 245.0 Hz, C2-Ar), 136.7 (C5a-Bd), 132.5 (C7-Bd), 130.2 (d,
J(CF) ¼ 13.6 Hz, C1-Ar), 128.8 (d, J(CF) ¼ 8.2 Hz, C4-Ar), 128.5 (d,
J(CF) ¼ 4.1 Hz, C6-Ar), 127.9 (C8-Bd), 125.3 (C8a-Bd), 124.2 (C5-Ar),
122.8 (C9-Bd), 122.0 (C5-Bd), 115.1 (d, J(CF) ¼ 22.3 Hz, C3-Ar), 70.6
(C3-Bd), 62.1 (C4-Bd), 18.9 (Me7-Bd), 18.4 (Me8-Bd); 15N NMR
for 6k: d 172.0 (C2-Bd), 142.1 (C1-Ar), 138.3 (C5a-Bd), 131.8 (C4-Ar),
129.0 (C2-Ar, C6-Ar), 128.9 (C8a-Bd), 128.0 (C3-Ar, C6-Ar), 124.2
(C7-Bd), 123.1 (C8-Bd), 121.8 (C5-Bd), 121.0 (C9-Bd), 72.2 (C3-Bd),
67.4 (C4-Bd); 13C{1H} NMR (126 MHz DMSO‑d6) for 6′k:
d 171.7 (C2-
Bd), 141.9 (C1-Ar), 140.63 (C5a-Bd), 131.8 (C4-Ar), 129.1 (C2-Ar, C6-
Ar), 128.3 (C7-Bd), 128.2 (C3-Ar, C5-Ar), 126.0 (C8a-Bd), 123.1 (C9-
Bd), 119.1 (C5-Bd), 119.0 (C8-Bd), 72.1 (C3-Bd), 66.8 (C4-Bd); 15N
(51 MHz, DMSO‑d6):
17H17FN2O2: C, 67.99; H, 5.71; F, 6.33; N, 9.33. Found: C, 67.87; H,
5.65; F, 6.44; N, 9.54.
d 128.7 (N1-Bd), 64.9 (N5-Bd); anal. calcd for
C
NMR (51 MHz, DMSO‑d6) for 6k:
NMR (51 MHz, DMSO‑d6) for 6′k:
d
129.6 (N1-Bd), 68.1 (N5-Bd); 15
129.0 (N1-Bd), 70.5 (N5-Bd);
N
d
4.4.14. 3-Hydroxy-4-(2-fluorophenyl)-7,8-dichloro-3,4,5-trihydro-
2H-benzo[b][1,4]diazepin-2(1H)-one (6n)
anal. calcd for C15H12Cl2N2O2: C, 55.75; H, 3.74; Cl, 21.94; N, 8.67.
Found: C, 55.83; H, 3.68; Cl, 21.71; N, 8.61.
4.4.12. 3-Hydroxy-4-(4-chlorophenyl)-7-nitro-3,4,5-trihydro-2H-
benzo[b][1,4]diazepin-2(1H)-one (60l)
Yield: 1.99 g (58%), white powder, mp 203e204 ꢁC; IR (KBr):
n
3611, 3318, 3198, 3078, 2930, 1679 cmꢀ1 1H NMR (500 MHz,
;
DMSO‑d6):
d
4.33 (1H, d, J ¼ 8.0 Hz, H3-Bd), 4.86 (1H, d, J ¼ 8.0 Hz,
Yield: 2.03 g (61%), yellow powder, mp 253e254 ꢁC; IR (KBr):
3387, 3204, 3068, 2879, 1666, 1334 cmꢀ1 1H NMR (500 MHz,
DMSO‑d6):
n
H4-Bd), 6.16 (1H, s, NH5-Bd), 7.07 (1H, s, H5-Bd), 7.10 (1H, s, H8-Bd),
7.18 (1H, d, J ¼ 8.0 Hz, H6-Ar), 7.20 (1H, dd, J ¼ 8.0, 7.5 Hz, H5-Ar),
7.35 (1H, dd, J ¼ 13.3, 7.6 Hz, H3-Ar), 7.42 (1H, ddd, J ¼ 7.6, 7.5,
1.6 Hz, H4-Ar), 10.01 (1H, s, NH1-Bd); 13C{1H} NMR (126 MHz,
;
d
4.28 (1H, dd, J ¼ 7.4 Hz, J ¼ 5.3 Hz, H3-Bd), 4.71 (1H, dd,
J ¼ 7.4 Hz, J ¼ 2.7 Hz, H4-Bd), 5.57 (1H, d, J ¼ 5.3 Hz, OH), 6.45 (1H, d,
J ¼ 2.7 Hz, NH5-Bd), 7.08 (1H, d, J ¼ 8.7 Hz, H8-Bd), 7.37 (2H, d,
J ¼ 8.6 Hz, H2-Ar, H6-Ar), 7.41 (2H, d, J ¼ 8.6 Hz, H3-Ar, H5-Ar), 7.60
(1H, dd, J ¼ 8.7 Hz, J ¼ 2.5 Hz, H7-Bd), 7.80 (1H, d, J ¼ 2.5 Hz, H5-Bd),
DMSO‑d6):
d
171.6 (C2-Bd), 159.8 (d, J(CF) ¼ 245.1 Hz, C2-Ar), 139.9
(C5a-Bd), 129.4 (d, J(CF) ¼ 8.3 Hz, C4-Ar), 129.0 (d, J(CF) ¼ 4.2 Hz,
C6-Ar), 128.7 (d, J(CF) ¼ 13.3 Hz, C1-Ar), 126.7 (C8a-Bd), 125.7 (C8-
Bd), 124.3 (d, J(CF) ¼ 2.6 Hz, C5-Ar), 122.4 (C9-Bd), 120.0 (C5-Bd),
119.7 (C7-Bd), 115.2 (d, J(CF) ¼ 22.0 Hz, C3-Ar), 71.7 (C3-Bd), 61.1
10.29 (1H, s, NH1-Bd); 13C{1H} NMR (126 MHz, DMSO‑d6):
d 171.8
(C2-Bd), 143.5 (C7-Bd), 141.0 (C1-Ar), 139.8 (C5a-Bd), 132.9 (C8a-
Bd), 131.9 (C4-Ar), 128.9 (C2-Ar, C6-Ar), 128.1 (C3-Ar, C5-Ar), 121.4
(C9-Bd), 114.1 (C8-Bd), 113.8 (C5-Bd), 73.9 (C3-Bd), 65.7 (C4-Bd);
(C4-Bd); 15N NMR (51 MHz, DMSO‑d6):
d 128.7 (N1-Bd), 68.4 (N5-
Bd); calcd for C15H11Cl2FN2O2: C, 55.81; H, 3.25; Cl, 20.78; F, 5.57
(Cl þ F, 26.35); N, 8.21. Found: C, 55.89; H, 3.45; Cl þ F, 26.66; N,
8.34.
15N NMR (51 MHz, DMSO‑d6):
d
371.2 (NO2), 133.2 (N1-Bd), 71.1
(N5-Bd); anal. calcd for C15H12ClN3O4: C, 53.98; H, 3.62; Cl, 10.62; N,

10
V.A. Mamedov et al. / Tetrahedron 76 (2020) 131478
4.4.15. 3-Hydroxy-4-(4-nitrophenyl)-3,4,5-trihydro-2H-benzo[b]
[1,4]diazepin-2(1H)-one (6o)
Yield: 2.95 g (80%), tan powder, mp 273e275 ꢁC; IR (KBr):
3367, 3188, 3073, 2963, 1713, 1678, 1518, 1495, 1347, 1107 cmꢀ1; 1H
NMR (500 MHz, DMSO‑d6):
n
d
4.31 (1H, d, J ¼ 8.1 Hz, H3-Bd), 4.77
(1H, d, J ¼ 8.1 Hz, H4-Bd), 5.25 (1H, s, NH5-Bd), 7.11 (1H, s, H5-Bd),
7.12 (1H, s, H8-Bd), 7.62 (2H, d, J ¼ 8.7 Hz, H2-Ar, H6-Ar), 8.22 (2H, d,
J ¼ 8.7 Hz, H3-Ar, H5-Ar), 10.02 (1H, s, NH1-Bd); 13C{1H} NMR
(126 MHz, DMSO‑d6):
d 171.4 (C2-Bd), 149.8 (C1-Ar), 146.9 (C4-Ar),
139.65 (C5a-Bd), 128.5 (C2-Ar, C6-Ar), 127.2 (C7-Bd), 125.8 (C8a-
Bd), 123.3 (C3-Ar, C5-Ar), 122.5 (C9-Bd), 120.3 (C5-Bd), 120.2 (C8-
Bd), 72.6 (C3-Bd), 66.3 (C4-Bd); calcd for C15H11Cl2N3O4: C, 48.93;
H, 3.01; Cl, 19.26; N, 11.41. Found: C, 48.78; H, 3.23; Cl, 19.46; N,
11.59.
Yield: 2.18 g (73%), brown powder, mp 240e241 ꢁC; IR (KBr):
n
3354, 3179, 3064, 2936, 1693, 5120, 1344, 1110 cmꢀ1 1H NMR
;
4.4.18. 3-Hydroxy-4-(4-nitrophenyl)-7,8-difluoro-3,4,5-trihydro-
2H-benzo[b][1,4]diazepin-2(1H)-one (6r)
(500 MHz, DMSO‑d6):
d
4.19 (1H, dd, J ¼ 9.1 Hz, J ¼ 6.3 Hz, H3-Bd),
4.65 (1H, d, J ¼ 9.1 Hz, H4-Bd), 5.11 (1H, d, J ¼ 6.3 Hz, OH), 5.73 (s,
1H, NH5-Bd), 6.87 (1H, ddd, J ¼ 7.8, 7.4, 1.2 Hz, H7-Bd), 6.93 (1H, dd,
J ¼ 7.4, 1.2 Hz, H5-Bd), 6.96 (1H, dd, J ¼ 7.4, 1.4 Hz, H8-Bd), 6.99 (1H,
ddd, J ¼ 7.8, 7.4,1.4 Hz, H6-Bd), 7.58 (2H, d, J ¼ 8.7 Hz, H2-Ar, H6-Ar),
8.21 (2H, d, J ¼ 8.7 Hz, H3-Ar, H5-Ar), 9.94 (s, 1H, NH1-Bd); 13C{1H}
NMR (126 MHz, DMSO‑d6): d 171.7 (C2-Bd),151.2 (C1-Ar),146.7 (C4-
Ar), 138.9 (C5a-Bd), 128.4 (C2-Ar, C6-Ar), 128.1 (C8a-Bd), 125.0 (C7-
Bd), 123.2 (C3-Ar, C5-Ar), 122.0 (C9-Bd), 121.0 (C5-Bd), 120.6 (C8-
Bd), 71.4 (C3-Bd), 67.9 (C4-Bd); 15N NMR (51 MHz, DMSO‑d6):
d
371.5 (NO2), 129.4 (N1-Bd), 66.4 (N5-Bd); anal. calcd for
15H13N3O4: C, 60.20; H, 4.38; N, 14.04. Found: C, 60.49; H, 4.43; N,
Yield: 2.65 g (79%), grey powder, mp 273e274 ꢁC; IR (KBr):
3465, 3370, 3195, 3084, 2977, 1670, 1515, 1336, 1101 cmꢀ1; 1H NMR
(500 MHz, DMSO‑d6):
n
C
14.22.
d
4.26 (1H, dd, J ¼ 8.9, 4.0 Hz, H3-Bd), 4.68 (d,
J ¼ 8.9 Hz, 1H, H4-Bd), 5.46 (1H, d, J ¼ 4.0 Hz, OH), 5.88 (s, 1H, NH5-
Bd), 6.93 (1H, dd, J ¼ 12.2, 8.7 Hz, H5-Bd), 6.98 (1H, dd, J ¼ 11.6,
8.4 Hz, H8-Bd), 7.60 (2H, d, J ¼ 8.8 Hz, H2-Ar, H6-Ar), 8.22 (2H, d,
J ¼ 8.8 Hz, H3-Ar, H5-Ar), 9.96 (s, 1H, NH1-Bd); 13C{1H} NMR
4.4.16. 3-Hydroxy-4-(4-nitrophenyl)-7,8-dimethyl-3,4,5-trihydro-
2H-benzo[b][1,4]diazepin-2(1H)-one (6p)
(126 MHz, DMSO‑d6):
d 171.7 (C2-Bd), 150.4 (C1-Ar), 146.8 (C4-Ar),
145.5 (dd, J(CF) ¼ 338.2 Hz, J(CF) ¼ 13.6 Hz, C8-Bd), 143.6 (dd,
J(CF) ¼ 332.5 Hz, J(CF) ¼ 13.4 Hz, C7-Bd), 136.1 (d, J(CF) ¼ 7.8 Hz,
C5a-Bd), 128.5 (C2-Ar, C5-Ar), 124.5 (d, J(CF) ¼ 7.7 Hz, C8a-Bd),
123.3 (C8a-Bd), 123.3 (C3-Ar, C5-Ar), 110.2 (d, J(CF) ¼ 19.9 Hz, C9-
Bd), 108.6 (d, J(CF) ¼ 19.2 Hz, C5-Bd), 71.6 (C3-Bd), 67.8 (C4-Bd);
15N NMR (51 MHz, DMSO‑d6):
d 371.1 (NO2), 128.3 (N1-Bd), 66.3
(N5-Bd); anal. calcd for C15H11F2N3O4: C, 53.74; H, 3.31; F, 11.33; N,
12.53. Found: C, 53.58; H, 3.27; F, 11.41; N, 12.59.
Yield: 2.55 g (78%), tan powder, mp 266e267 ꢁC; IR (KBr):
n
3378, 3195, 3080, 2917, 1708, 1666, 1511, 1338, 1103 cmꢀ1; 1H NMR
(500 MHz, DMSO‑d6):
d
2.12 (6H, s, 2Me), 4.15 (1H, dd, J ¼ 9.4 Hz,
4.4.19. 3-Hydroxy-4-(4-nitrophenyl)-8-chloro-3,4,5-trihydro-2H-
benzo[b][1,4]diazepin-2(1H)-one (6s) and 3-hydroxy-4-(4-
nitrophenyl)-7-chloro-3,4,5-trihydro-2H-benzo[b][1,5]diazepin-
2(1H)-one (6’s)
J ¼ 5.3 Hz, H3-Bd), 4.58 (1H, d, J ¼ 9.4 Hz, H4-Bd), 5.00 (1H, d,
J ¼ 5.3 Hz, OH), 5.43 (1H, s, NH5-Bd), 6.72 (1H, s, H5-Bd), 6.74 (1H, s,
H8-Bd), 7.56 (2H, d, J ¼ 8.7 Hz, H2-Ar, H6-Ar), 8.20 (2H, d, J ¼ 8.7 Hz,
H3-Ar, H6-Ar), 9.81 (1H, s, NH1-Bd); 13C{1H} NMR (126 MHz,
DMSO‑d6): d 171.8 (C2-Bd), 151.5 (C1-Ar), 146.7 (C4-Ar), 136.5 (C5a-
Bd), 132.9 (C7-Bd), 128.6 (C8-Bd), 128.4 (C2-Ar, C6-Ar), 126.0 (C8a-
Bd), 123.2 (C3-Ar, C5-Ar), 123.0 (C9-Bd), 122.4 (C5-Bd), 71.1 (C3-Bd),
68.5 (C4-Bd), 18.9 (Me8-Bd), 18.5 (Me7-Bd); anal. calcd for
C
17H17N3O4: C, 62.38; H, 5.23; N, 12.84. Found: C, 62.48; H, 5.43; N,
12.72.
4.4.17. 3-Hydroxy-4-(4-nitrophenyl)-7,8-dichloro-3,4,5-trihydro-
2H-benzo[b][1,4]diazepin-2(1H)-one (6q)
Yield: 2.43 g (73%); 1H NMR (500 MHz, DMSO‑d6) for 6s:
d 4.25
(1H, dd, J ¼ 9.6, 6.1 Hz, H3-Bd), 4.70 (1H, d, J ¼ 9.6 Hz, H4-Bd), 5.30
(1H, d, J ¼ 6.1 Hz, OH), 5.94 (1H, s, NH5-Bd), 6.91 (1H, d, J ¼ 8.5 Hz,
H5-Bd), 6.97 (1H, d, J ¼ 2.4 Hz, H8-Bd), 7.01 (1H, dd, J ¼ 8.5, 2.4 Hz,
H6-Bd), 7.58 (2H, d, J ¼ 8.6 Hz, H2-Ar, H6-Ar), 8.20 (2H, d, J ¼ 8.6 Hz,
H3-Ar, H5-Ar), 9.98 (s, 1H, NH1-Bd); 1H NMR (500 MHz, DMSO‑d6)
for 6’s:
d
4.25 (1H, dd, J ¼ 9.5, 6.0 Hz, H3-Bd), 4.72 (1H, d, J ¼ 9.5 Hz,
H4-Bd), 5.28 (1H, d, J ¼ 6.0 Hz, OH), 6.08 (1H, s, NH5-Bd), 6.83 (1H,
dd, J ¼ 8.4, 2.3 Hz, H7-Bd), 6.94 (1H, d, J ¼ 8.4 Hz, H8-Bd), 6.96 (1H,

V.A. Mamedov et al. / Tetrahedron 76 (2020) 131478
11
d, J ¼ 2.3 Hz, H5-Bd), 7.60 (2H, d, J ¼ 8.6 Hz, H2-Ar, H6-Ar), 8.23 (d,
4.4.22. 6,7-Dimethyl-3-(4-methylbenzyl)quinoxalin-2(1H)-one
(4u)
2H, J ¼ 8.6 Hz, H3-Ar, H5-Ar), 9.98 (1H, s, NH1-Bd); 13C{1H} NMR
(126 MHz, DMSO‑d6) for 6s:
d 171.6 (C2-Bd), 150.6 (C1-Ar), 146.7
(C4-Ar), 138.1 (C5a-Bd), 129.0 (C8a-Bd), 128.4 (C2-Ar, C6-Ar), 124.4
(C7-Bd), 123.3 (C3-Ar, C5-Ar), 123.2 (C8-Bd), 121.8 (C5-Bd), 121.1
(C9-Bd), 72.0 (C3-Bd), 67.3 (C4-Bd); 13C{1H} NMR (126 MHz,
DMSO‑d6) for 6’s: d 171.3 (C2-Bd),150.3 (C1-Ar),146.8 (C4-Ar),140.4
(C5a-Bd), 128.5 (C2-Ar, C6-Ar), 128.3 (C7-Bd), 126.1 (C8a-Bd), 123.4
(C3-Ar, C5-Ar), 123.3 (C9-Bd), 119.3 (C8-Bd),119.2 (C5-Bd), 72.0 (C3-
Bd), 66.7 (C4-Bd); 15N NMR (51 MHz, DMSO‑d6) for 6s:
d
371.3
(NO2), 129.8 (N1-Bd), 66.1 (N5-Bd); 15N NMR (51 MHz, DMSO‑d6)
for 6’s: 371.3 (NO2), 129.0 (N1-Bd), 69.2 (N5-Bd); calcd for
15H12ClN3O4: C, 53.98; H, 3.62; Cl, 10.62; N, 12.59. Found: C, 53.73;
d
Yield: 1.70 g (61%), white powder, mp 240e241 ꢁC; IR (KBr):
n
2916, 2862, 1658 cmꢀ1; 1H NMR (500 MHz, DMSO‑d6):
d
2.24 (3H, s,
C
H, 3.67; Cl, 10.46; N, 12.63.
Me-Ar), 2.25 (3H, s, Me6-Q), 2.27 (3H, s, Me7-Q), 4.03 (2H, s, CH2),
7.02 (1H, s, H8-Q), 7.07 (2H, d, J ¼ 7.9 Hz, H3-Ar, H5-Ar), 7.19 (2H, d,
J ¼ 7.9 Hz, H2-Ar, H6-Ar), 7.48 (1H, s, H5-Q), 12.19 (s, 1H, NH); 13C
4.4.20. 6,7-Dimethyl-3-benzylquinoxalin-2(1H)-one (4b) and 3-
hydroxy-4-phenyl-7,8-dimethyl-3,4,5-trihydro-2H-benzo[b][1,4]
diazepin-2(1H)-one (6b)
{1H} NMR (126 MHz, DMSO‑d6):
d 159.0 (C2-Q), 154.5 (C3-Q), 139.0
(C6-Q), 135.2 (C4-Ar), 134.5 (C1-Ar), 131.7 (C7-Q), 130.1 (C8a-Q),
129.9 (C4a-Q), 128.9 (C2-Ar, C6-Ar), 128.8 (C3-Ar, C5-Ar), 128.1 (C5-
Q), 115.2 (C8-Q), 38.4 (CH2), 20.5 (Me6-Q), 19.6 (Me7-Q), 18.8 (Me-
Ar); anal. calcd for C18H18N2O: C, 77.67; H, 6.52; N, 10.06. Found: C,
77.51; H, 6.37; N, 10.24.
4.4.23. 6,7-Difluoro-3-(4-methylbenzyl)quinoxalin-2(1H)-one (4y)
1H NMR (400 MHz, DMSO‑d6) for 4b:
(1H, s, Me7-Q), 4.09 (2H, s, CH2), 7.04 (1H, s, H8-Q), 7.14e7.38 (5H,
m, Ph); 1H NMR (400 MHz, DMSO‑d6) for 6b:
2.10 (3H, s, Me8-Bd),
d 2.26 (1H, s, Me6-Q), 2.29
d
2.12 (3H, s, Me7-Bd), 4.09 (1H, d, J ¼ 9.3 Hz, H3-Bd), 4.39 (1H, d,
J ¼ 9.3 Hz, H4-Bd), 4.79 (1H, d, J ¼ 6.2 Hz, OH), 5.22 (1H, s, NH5-Bd),
6.71 (1H, s, H6-Bd), 6.73 (1H, s, H9-Bd), 7.22e7.38 (5H, m, Ph), 9.78
(1H, s, NH1-Bd).
Yield: 1.23 g (43%), tan powder, mp 222e224 ꢁC; IR (KBr):
2920, 2855, 1682, 1519 cmꢀ1; 1H NMR (500 MHz, DMSO‑d6):
2.24
n
d
(3H, s, Me), 4.04 (2H, s, CH2), 7.08 (2H, d, J ¼ 7.9 Hz, H3-Ar, H5-Ar),
7.18 (2H, d, J ¼ 7.9 Hz, H2-Ar, H6-Ar), 7.19 (1H, dd, J ¼ 11.7, 7.9 Hz,
H8-Q), 7.81 (1H, dd, J ¼ 11.1, 8.2 Hz, H5-Q),12.45 (1H, s, NH); 13C{1H}
4.4.21. 3-(4-Methylbenzyl)quinoxalin-2(1H)-one (4t)
NMR (126 MHz, DMSO‑d6):
d 161.2 (C2-Q), 154.1 (C3-Q), 150.0 (dd,
J(CF) ¼ 249.4 Hz, J(CF) ¼ 14.8 Hz, C6-Q), 145.6 (dd, J(CF) ¼ 241.4 Hz,
J(CF) ¼ 14.1 Hz, C7-Q), 135.4 (C4-Ar), 133.9 (C1-Ar), 129.2 (d,
J(CF) ¼ 9.3 Hz, C8a-Q), 128.9 (C2-Ar, C6-Ar), 128.8 (C3-Ar, C5-Ar),
127.9 (d, J(CF) ¼ 9.1 Hz, C4a-Q),115.9 (d, J(CF) ¼ 17.9 Hz, C5-Q),102.9
(d, J(CF) ¼ 21.9 Hz, C8-Q), 38.4 (CH2), 20.5 (Me); 15N NMR (51 MHz,
DMSO‑d6):
d 324.4 (N4-Q), 149.7 (N1-Q); anal. calcd for
C16H12F2N2O: C, 67.13; H, 4.23; F, 13.27; N, 9.79. Found: C, 67.45; H,
4.27; F, 13.35; N, 9.68.
Yield: 1.30 g (52%), white powder, mp 197e198 ꢁC (mp
4.4.24. 3-(4-Methoxybenzyl)quinoxalin-2(1H)-one (4w)
156e158 ꢁC11b); IR (KBr):
n ;
2926, 2838, 1661 cmꢀ1 1H NMR
(500 MHz, DMSO‑d6): d 2.24 (3H, s, Me), 4.07 (2H, s, CH2), 7.08 (2H,
d, J ¼ 7.9 Hz, H3-Ar, H5-Ar), 7.20 (2H, d, J ¼ 7.9 Hz, H2-Ar, H6-Ar),
7.26 (1H, dd, J ¼ 7.7 Hz, J ¼ 7.6 Hz, H6-Q), 7.28 (1H, d, J ¼ 7.7 Hz, H8-
Q), 7.47 (1H, ddd, J ¼ 7.7, 7.6, 1.1 Hz, H7-Q), 7.71 (1H, dd, J ¼ 7.7,
1.1 Hz, H5-Q), 12.34 (1H, s, NH); 13C{1H} NMR (126 MHz, DMSO‑d6):
d
160.4 (C2-Q), 154.5 (C3-Q), 135.2 (C4-Ar), 134.3 (C1-Ar), 131.9
(C8a-Q), 131.6 (C4a-Q), 129.6 (C7-Q), 128.9 (C2-Ar, C6-Ar), 128.8
(C3-Ar, C5-Ar), 128.1 (C5-Q), 123.1 (C6-Q), 115.2 (C8-Q), 38.5 (CH2),
20.5 (Me); 15N NMR (51 MHz, DMSO‑d6):
d 329.3 (N4-Q), 149.6 (N1-
Q); anal. calcd for C16H14N2O: C, 76.78; H, 5.64; N, 11.19. Found: C,
76.63; H, 5.68; N, 11.01.
Yield: 1.54 g (58%), yellow powder, mp 187e189 ꢁC (198e199 ꢁC
[11a], 138e140 ꢁC [11b], 188e189 ꢁC12a); IR (KBr):
n 2957, 2835,

12
V.A. Mamedov et al. / Tetrahedron 76 (2020) 131478
1660, 1506, 1245 cmꢀ1; 1H NMR (500 MHz, DMSO‑d6):
d
3.70 (3H, s,
Crystallographic Data Centre, CCDC number is 2014915 respec-
tively. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK,
(fax: þ44-(0)1223e336033 or e-mail: deposit@ccdc.cam.ac.UK).
OMe), 4.04 (2H, s, CH2), 6.84 (2H, d, J ¼ 8.6 Hz, H3-Ar, H5-Ar), 7.25
(2H, d, J ¼ 8.6 Hz, H2-Ar, H6-Ar), 7.26 (1H, dd, J ¼ 8.2, 7.7 Hz, H6-Q),
7.28 (1H, d, J ¼ 7.9 Hz, H8-Q), 7.47 (1H, ddd, J ¼ 7.9, 7.7,1.3 Hz, H7-Q),
7.71 (1H, dd, J ¼ 8.2, 1.3 Hz, H5-Q), 12.23 (1H, s, NH1-Q); 13C{1H}
NMR (126 MHz, DMSO‑d6):
d 160.5 (C2-Q), 157.8 (C3-Q), 154.4 (C3-
Declaration of competing interest
Q), 131.9 (C8a-Q), 131.6 (C4a-Q), 130.1 (C2-Ar, C6-Ar), 129.6 (C7-Q),
129.1 (C1-Ar), 128.1 (C5-Q), 123.1 (C6-Q), 115.2 (C8-Q), 113.7 (C3-Ar,
C5-Ar), 54.9 (OMe) 38.0 (CH2); 15N NMR (51 MHz, DMSO‑d6):
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
d
328.9 (N4-Q),149.7 (N1-Q); anal. calcd for C16H14N2O2: C, 72.16; H,
5.30; N, 10.52. Found: C, 71.99; H, 5.26; N, 10.67.
Acknowledgements
4.4.25. 6,7-Dichloro-3-(4-methoxybenzyl)quinoxalin-2(1H)-one
(4x)
The authors gratefully acknowledge the CSF-SAC FRC KazSC RAS
for providing necessary facilities to carry out this work. This work
was financially supported in part by the Russian Science Founda-
tion (Project No 18-13-00315).
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2020.131478.
References
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d 3.70 (3H, s, OMe), 4.03 (2H, s, CH2),
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