The reported formation of 5H-dibenzo[b,e][1,4]diazepin-11(10H)-ones in the noncatalyzed, base-promoted double arylation of anthranilamide revisited. Correction of some product structures

Article abstract of DOI:10.1002/jhet.4311

The base-promoted reaction of 2-halonitro- or 1,2-dihalobenzenes with anthranilamide reported by Cao, Ma et al. (Synthesis 2013, 45, 111) was reinvestigated. Some of the products reported, which have been identified as dibenzodiazepinones, are actually be

Full text of DOI:10.1002/jhet.4311

Received: 10 April 2021
DOI: 10.1002/jhet.4311
Revised: 14 May 2021
Accepted: 26 May 2021
A R T I C L E
The reported formation of 5H-dibenzo[b,e][1,4]diazepin-11
(10H)-ones in the noncatalyzed, base-promoted double
arylation of anthranilamide revisited. Correction of some
product structures
1
| Bogdan Wilk2 | Piotr Cmoch1 | Andrzej Kwast1
ꢀ
Zbigniew Wrobel
1Institute of Organic Chemistry, Polish
Academy of Sciences, Warsaw, Poland
Abstract
2Monmouth University, West Long
Branch, New Jersey, USA
The base-promoted reaction of 2-halonitro- or 1,2-dihalobenzenes with
anthranilamide reported by Cao, Ma et al. (Synthesis 2013, 45, 111) was
reinvestigated. Some of the products reported, which have been identified as
dibenzodiazepinones, are actually benzoxazole derivatives. In this paper, the
correct structures of these products were established and confirmed by inde-
pendent synthesis. For four other products, the supposed structures were
found to be incompatible with the dibenzodiazepinones that were synthesized
by the reliable method used in this work.
Correspondence
ꢀ
Zbigniew Wrobel, Institute of Organic
Chemistry, Polish Academy of Sciences,
Kasprzaka 44/52, 00-266 Warsaw, Poland.
Email: zbigniew.wrobel@icho.edu.pl
Funding information
Polska Akademia Nauk
K E Y W O R D S
benzoxazoles, dibenzodiazepinones, nitro compounds
1 | INTRODUCTION
nitroacid 2a, gave a spectrum that was distinctly different
from that of the compound (originally numbered as 3g)
Working on the synthesis of 5H-dibenzo[b,e][1,4]dia-
zepin-11(10H)-one skeleton by the intramolecular reduc-
tive condensation of a nitro group with carboxylic acids,
promoted by phosphorus (III) compounds [1], we were
interested in other methods leading to such structures.
We compared efficiency, generality, and selectivity of
them in order to find possible advantages of our
approach. Our attention was particularly drawn to the
method of the synthesis of diazepinones published by
Cao and Ma [2]. The method is based on the base-
promoted arylation of anthranilamide by o-halonitro-
and o-dihalobenzenes. The advantages of this reaction
are simple starting materials, mild reaction conditions,
easy procedure, and reasonable yields. However, we
found that reported NMR spectra of some products
obtained by that method (Scheme 1, method a), and
obtained by us previously (method b) [1], did not match.
For a representative example, 8-chloro-5H-dibenzo[b,e]
[1,4]diazepin-11(10H)-one (1a), obtained by us from
[2] claimed to have the same structure. This finding con-
cerns also 8-trifluoromethyl derivative 1b obtained from
2b [1] and reported compound numbered as 3e [2].
Therefore, we decided to try to explain this discrepancy
(copies of the NMR spectra of all synthesized compounds,
shown side by side with reproduced spectra of the related
compounds described in ref [2] can be found in
supporting information) (Appendix S1).
2 | RESULTS AND DISCUSSION
Considering the structure of the starting nitroacids 2 and
the chemistry of their cyclization, one could be sure that
the structures of 1a and 1b are correct. The course of the
reaction described in the cited paper seems to be less
obvious. To elucidate the problem, we tried to reproduce
the reported result. In our hands, the reaction of
anthranilamide (3) with 2,5-dichloronitrobenzene (4a)
J Heterocyclic Chem. 2021;1–7.
wileyonlinelibrary.com/journal/jhet
© 2021 Wiley Periodicals LLC.
1

2
WRÓBEL ET AL.
carried out under Cs2CO3/DMF/150ꢀC conditions
afforded a complex mixture from which we isolated less
than 5% of a distinct product. The 1H NMR and 13C NMR
spectra of this compound matched exactly those reported
for 3g. Detailed inspection of the spectra and some con-
sideration of possible reaction pathways let us propose a
correct structure for compound 3g having the same molar
mass as 1a. The structure of 3g was confirmed by inde-
pendent synthesis (5a in Table 1), detailed NMR spectra
including most diagnostic 15N spectra [3] (Figure 1), and
finally by X-ray measurements (Figure 2) (X-ray comput-
ing details can be found in supporting information).
The independent synthesis of 5a as well as of a few
selected (2-aminophenyl)benzoxazoles 5b–e related to
the compounds that were referred to as dibenzodiazepinones
[2] was performed by adaptation of a known method [4]
in which 2-nitrobenzanilide, obtained by acylation of
appropriate ortho-aminophenol 7 with 2-nitrobenzoyl
chloride, was cyclized without isolation to 8, then sub-
jected to reduction of the nitro group (Table 1).
On the basis of the NMR spectra, three of the
obtained benzoxazoles 5a–c appeared identical to
the compounds described as dibenzodiazepinones 3g, 3a,
and 3c in the cited paper [2]. The remaining two (3e and
Cl
7.90
H
129.02
111.04
148.92
C
124.97
CH
7.40
O
C 119.90
H
163.53
128.02 C
HC
140.29 H
N
7.74
105.79
115.45
[-147.2]
148.94
HC
132.88
C 116.12 NH2
H
[-307.8]
3g = 5a
O
R
X
method a (ref.[2])
Cs2CO3
DMF
NH2
O
[-246.9]
+
H
NH2
??
Cl
N
167.61
4a R = Cl, X = NO2
4b R = CF3, X = Cl
120.41
132.16
131.17
O
H
3
N
122.32
149.75
Cl
120.91
R
126.22
123.94
N
H
CO2H
N
138.68
133.46
H
1a (3g) R = Cl
1b (3e) R = CF3
PBu3
NH
119.06
121.00
[-290.7]
NO2 method b(ref.[1])
1a = 3g
2a R = Cl
2b R = CF3
R
FIGURE 1 Comparison of the NMR assignments for the
reported and actual structures of 3g [2]
SCHEME 1 The questioned [2] and the reliable [1] route to 1
TABLE 1 The independent synthesis of (2-aminophenyl)benzoxazoles 5
1
O
7
4
R
R
R
COCl
NO2
HO
1. Py
SnCl2·2H2O
O
N
6
2
+
5
3N
2. TsOH
H2N
NO2
NH2
6
7a-e
2-Aminophenol 7
R in
5a-e
8a-e
8
(2-Aminophenyl)benzoxazole 5
Entry
Isolated yield %
Isolated yield %
R
1
2
3
4
5
5-Cl
8a
8b
8c
8d
8e
55
53
21
54
54
5a
5b
5c
5d
5e
99
89
45
98
75
6-Cl
6-F
5-F
5-CN
6-Me
5-CF3
6-CN
4-Me
6-CF3

WRÓBEL ET AL.
3
CO2H
NH
O
H
N
9
1
PBu3
2
8
NO2
140 oC
N
6 R7
5
3
H
4
1b1 R = 8-CF3
R
1c R = 6-Me
1d R = 9-Me
1e R = 6-Cl
2b-f, 2h
CuCN
1f R = 6-Br
1g R = 6-CN
1h1 R = 7-CF3
FIGURE 2 ORTEP view of 2-(2-aminophenyl)-
6-chlorobenzoxazole (5a)
SCHEME 2 The synthesis of dibenzodiazepinones related to
the products reported [2]. The synthesis of 1b and 1h taken from
our previous paper [1]
3f) do not seem to be benzoxazole derivatives as their
spectra do not match with respective 5e and 5d.
Unfortunately, more extensive discussion of the reaction
under consideration is rather difficult as our attempts to
reproduce some of the reported results were
unsuccessful.
Looking at the structure of the reactants and the reac-
tion conditions (method a, Scheme 1), one might con-
sider the possibility of a different sequence of substitution
in which the first more activated leaving group (in this
case, chlorine) is replaced by the carboxamide nitrogen
anion rather than by the arylamine anion. This would
lead to isomeric dibenzazepinones which differ from the
expected products by positions of substituents (position
7- vs 8- and 6- vs 9-).
For the elucidation of structures of these and other
reported products, a number of appropriate, differently
substituted dibenzodiazepinones 1 were obtained by
unambiguous cyclization of nitroacids 2 (Scheme 2,
includes some earlier results [1]). Their spectra were
compared with those reported [2] for the respective prod-
ucts 3b–f.
3 | CONCLUSION
The base-promoted reaction of o-halonitro- and o-
dihalobenzenes with anthranilamide, carried out under
the reported reaction conditions [2], seems to proceed on
several concurrent pathways depending on the starting
materials, giving unpredictable or misleading results.
Therefore, three of the reported products that have been
identified as dibenzodiazepinones are actually
aminobenzoxazole derivatives. Four other products
showed spectra that are inconsistent with spectra of
dibenzodiazepinones synthesized by the reliable method;
thus, they are identified and described incorrectly.
On this basis, the possible formation of isomeric prod-
ucts for 3e and 3f was excluded. Both 6-methyl- (1c) and
9-methyl- (1d) dibenzodiazepinones turned out to be dif-
ferent from compound 3f. Possible 7-CF3 and 8-CF3 iso-
meric
dibenzodiazepinones,
which
have
been
4 | EXPERIMENTAL SECTION
synthesized and described in our previous paper [1] also
have inconsistent spectra with a compound reported as
3e [2].
Melting points were recorded in open capillary and are
1
uncorrected. The H, 13C, and 15N NMR spectra of all
The spectra of 6-chloro- (1e) and 6-cyano- (1g)
dibenzodiazepinones proved incorrectness of the reported
structures of the compounds numbered as 3b and 3d.
The results of the verification of the reported products [2]
are collected in Table 2. Interestingly, the reported spe-
cial example of the reaction of N-methylanthranilamide
with 2,3-difluorobenzonitrile that served as evidence of
the proposed mechanism (like path a in Scheme 1) gave
the expected 10-methyl-11-oxo-10,11-dihydro-5H-dibenzo
[b,e][1,4]-diazepine-9-carbonitrile that was proved by sin-
gle crystal X-ray analysis of the final product but it was
compounds studied were measured at temperature 298 K
in CDCl3 or deuterated dimethyl sulfoxide (DMSO-d6)
solutions with a Varian vnmrs600 or Varian vnmrs500
using tetramethylsilane (TMS) as the internal standard.
Two-dimensional, heteronuclear spectra were recorded
with a Varian vnmrs600 aparatus in DMSO-d6. Mass
spectra (EI, 70 eV) were obtained on an AutoSpec Pre-
mier (Waters) spectrometer. For ESI+ and ESIÀ mea-
surements a Maldi SYNAPT G2-S HDMS (Waters) was
used. Accurate mass measurements were obtained using
magnetic sector mass analyzer (EI) or TOF analyzer
(ESI). Silica gel Merck 60 (230–400 mesh) was used for
the only
correctly
identified
compound
[2].

4
WRÓBEL ET AL.
TABLE 2 Summary of the
Declared, incorrect structure
(original labels in italics) [2]
Spectral data
compatibility
Synthesized and confirmed
structure (this work)
erroneously reported products [2]
(method a in Scheme 1)
O
H
Cl
O
Matches with
N
Cl
N
NH2
N
H
3g
5a
O
H
F
O
N
Matches with
Matches with
N
F
NH2
N
H
3a
5b
O
H
CN
O
N
N
CN
NH2
N
H
3c
5c
1e
O
H
O
Inconsistent
Inconsistent
Inconsistent
H
N
N
N
H
N
H
Cl
Cl
3b
O
H
O
O
H
N
N
N
H
N
H
NC
NC
3d
1g
O
H
H
N
N
CF3
CF3
1ba
a
N
N
H
H
3e
O
H
O
Inconsistent
H
N
N
N
H
N
H
3f
1d
aFrom our previous paper [1].
column chromatography. DMF was dried over CaH2, dis-
tilled, and stored over molecular sieves. All commercial
reagents were used without additional purification.
Single-crystal structural data of 5a were collected by
Bruker APEX-II CCD diffractometer. The structural solu-
tion and refinement process were done using ShelXL pro-
gram [5]. The molecular graphics and publication
material were generated using PLATON [6] and PublCIF
[7] programs.
added stepwise. The resulted mixture was allowed to
warm up to room temperature and stirred overnight. The
volatile components were then removed in vacuo and
the residue, crude product, was refluxed with TsOHÁH2O
(17.0 g, 82 mmol) in toluene with Dean-Stark trap for
2 days. After evaporation of the toluene, the residue was
diluted with EtOAc (200 mL), washed with water
(2 Â 100 mL), dried over Na2SO4, and evaporated. The
product was isolated using column chromatography
(SiO2, hexane–EtOAc) to obtain 2-nitrophenylbenz
oxazoles 8a–e.
4.1 | General procedure for the synthesis
of benzoxazoles 5a–e
2-Nitrophenylbenzoxazole
8
(1.0 mmol)
and
SnCl2Á2H2O (2.6 g, 10.0 mmol) were stirred in EtOAc
(30 mL) at room temperature for 24 h. The mixture was
then diluted with EtOAc, washed with water
(2 Â 50 mL), dried (Na2SO4) and the solvent was
removed under vacuum. The product (7a–e) was isolated
by column chromatography (SiO2, hexane–EtOAc).
To a solution of appropriate 2-aminophenol 7aÀe
(33.5 mmol) in dichloromethane (100 mL) was added
pyrridine (10 mL). The reaction mixture was cooled to
À20ꢀC and 2-nitrobenzoyl chloride (40.0 mmol) was

WRÓBEL ET AL.
5
4.2 | 6-Chloro-2-(2-nitrophenyl)
benzoxazole (8a)
(t, J = 7.6 Hz, 1H), 7.58 (d, J = 7.6 Hz, 1H), 7.85–7.93 (m,
2H), 8.12 (dd, J = 7.6, 1.2 Hz, 1H), 8.18 (dd, J = 7.6,
1.2 Hz, 1H). 13C NMR (125 MHz, DMSO-d6): δ = 19.2,
111.5, 123.3, 127.6, 128.6, 129.1, 133.5, 134.4, 136.0, 136.4,
143.3, 151.7, 153.3, 160.8. MS (EI): m/z (%) = 254
(77, [M]+), 181 (95), 134 (54), 120 (100), 104 (74). HRMS
(EI): m/z calcd for C14H10N2O3 [M]+: 254.0691; found:
254.0697.
Yield: 5.10 g (55%); pale beige solid; mp 112–113ꢀC (lit
[8]. 108–109ꢀC). 1H NMR (500 MHz, DMSO-d6): δ = 7.48
(dd, J = 8.5, 1.9 Hz, 1H), 7.85 (d, J = 8.5 Hz, 1H), 7.86–
7.92 (m, 2H), 8.02 (d, J = 1.9 Hz, 1H), 8.12 (dd, J = 7.9,
1.0 Hz, 1H), 8.16 (dd, J = 7.5, 1.5 Hz, 1H). 13C NMR
(125 MHz, DMSO-d6): δ = 112.2, 120.9, 121.8, 125.0,
126.2, 131.1, 131.7, 133.7, 140.4, 149.0, 151.0, 159.5. One
carbon signal remains unaccounted for. MS (EI): m/z
(%) = 274 (55, [M]+), 204 (62), 202 (85), 140 (61),
134 (72), 104 (100). HRMS (EI): m/z calcd for
C13H7N235ClO3 [M]+: 274.0145; found: 274.0144.
4.6 | 2-(2-Nitrophenyl)-
6-(trifluoromethyl)benzoxazole (8e)
1
Yield: 5.57 g (54%); colorless crystals; mp 101–102ꢀC. H
NMR (500 MHz, DMSO-d6): δ = 7.79 (dd, J = 8.4, 1.0 Hz,
1H), 7.89–7.95 (m, 2H), 8.05 (d, J = 8.4 Hz, 1H), 8.14 (dd,
J = 7.4, 1.6 Hz, 1H), 8.18 (dd, J = 7.4, 1.6 Hz, 1H), 8.30
(br s, 1H). 13C NMR (125 MHz, DMSO-d6): δ = 109.8 (q,
JFC = 4 Hz), 119.8, 121.7, 122.7 (q, JFC = 4 Hz), 124.4 (q,
4.3 | 6-Fluoro-2-(2-nitrophenyl)
benzoxazole (8b)
1
Yield: 4.55 g (53%); beige powder, mp 121ꢀC. H NMR
JFC = 273 Hz), 125.1, 127.1 (q, JFC = 32 Hz), 131.9, 133.8,
(500 MHz, DMSO-d6): δ = 7.36 (ddd, J = 9.8, 8.7, 2.4 Hz,
1H), 7.85 (dd, J = 8.7, 2.4 Hz, 1H), 7.90–7.97 (m, 3H),
8.14 (dd, J = 7.8, 1.3 Hz, 1H), 8.19 (dd, J = 7.3, 1.3 Hz,
1H). 13C NMR (125 MHz, DMSO-d6): δ = 99.8 (d,
JFC = 29 Hz), 113.7 (d, JFC = 25 Hz), 120.0, 121.5 (d,
JFC = 10 Hz), 124.9, 131.6, 133.5, 133.6, 138.0 (d,
JFC = 2 Hz), 149.0, 150.8 (d, JFC = 16 Hz), 159.4 (d,
JFC = 4 Hz), 160.9 (d, JFC = 243 Hz). MS (EI): m/z
(%) = 258 (67, [M]+), 213 (23), 186 (93), 134 (71),
124 (75), 104 (100). HRMS (EI): m/z calcd for
C13H7N2FO3 [M]+: 258.0441; found: 258.0448.
134.0, 144.4 (q, JFC = 1 Hz), 149.1, 150.3, 161.4. MS (EI):
m/z (%) = 308 (44, [M]+), 289 (28), 263 (35), 238 (51),
236 (62), 217 (35), 186 (39), 134 (67), 104 (100). HRMS
(EI): m/z calcd for C14H7N2F3O3 [M]+: 308.0409; found:
308.0417.
4.7 | 2-(2-Aminophenyl)-
6-chlorobenzoxazole (5a)
Yield: 242 mg (99%); pale yellow solid; mp 133–134ꢀC.
FT-IR: 3474, 3327, 1623, 1540, 1449 cmÀ1 1H NMR
.
(500 MHz, DMSO-d6): δ = 6.66 (ddd, J = 8.1, 7.0, 1.1 Hz,
1H), 6.88 (dd, J = 8.3, 1.0 Hz, 1H), 7.08 (s, 2H), 7.26 (ddd,
J = 8.3, 7.0, 1.3 Hz, 1H), 7.40 (dd, J = 8.0, 2.4 Hz, 1H),
7.74 (d, J = 8.4 Hz, 1H), 7.86 (dd, J = 8.0, 1.4 Hz,
1H), 7.90 (d, J = 2.0 Hz, 1H). 13C NMR (125 MHz,
DMSO-d6): δ = 106.2, 111.4, 115.9, 116.6, 120.3, 125.4,
128.5, 129.5, 133.3, 140.7, 149.38, 149.39, 164.0. MS (EI):
m/z (%) = 246 (51), 244 (100, [M]+), 228 (23), 181 (49).
HRMS (EI): m/z calcd for C13H9N235ClO [M]+: 244.0403;
found: 244.0411.
4.4 | 6-Cyano-2-(2-nitrophenyl)
benzoxazole (8c)
Yield: 1.86 g (21%); beige powder; mp 204–206ꢀC. 1H
NMR (500 MHz, DMSO-d6): δ = 7.92–8.00 (m, 3H), 8.08
(d, J = 8.3 Hz, 1H), 8.17–8.20 (m, 1H), 8.23–8.27 (m, 1H),
8.53 (dd, J = 1.5, 0.6 Hz, 1H). 13C NMR (125 MHz,
DMSO-d6): δ = 108.3, 116.1, 118.5, 119.1, 121.5, 124.6,
129.5, 131.6, 133.4, 133.7, 144.6, 148.6, 149.6, 161.3. MS
(EI): m/z (%) = 265 (28, [M]+), 220 (24), 193 (81),
164 (33), 134 (57), 104 (100). HRMS (EI): m/z calcd for
C14H7N3O3 [M]+: 265.0487; found: 265.0495.
4.8 | 2-(2-Aminophenyl)-
6-fluorobenzoxazole (5b)
4.5 | 4-Methyl-2-(2-nitrophenyl)
benzoxazole (8d)
Yield: 203 mg (89%); pale yellow solid; mp 125–127ꢀC.
FT-IR: 3402, 3368, 3277, 1624, 1546, 1479 cmÀ1. 1H NMR
(500 MHz, DMSO-d6): δ = 6.69 (ddd, J = 8.0, 7.1, 1.1 Hz,
1H), 6.91 (dd, J = 8.3, 0.5 Hz, 1H), 7.09 (s, 2H), 7.25–7.30
(m, 2H), 7.76 (dd, J = 8.4, 2.3 Hz, 1H), 7.79 (dd, J = 8.7,
4.9 Hz, 1H), 7.90 (dd, J = 8.0, 1.4 Hz, 1H). 13C NMR
Yield: 4.57 g (54%); colorless crystals; mp 108ꢀC (lit [9].
mp 104.3–108.8ꢀC). 1H NMR (500 MHz, DMSO-d6):
δ = 2.55, (s, 3H), 7.25 (d, J = 7.6 Hz, 1H), 7.36

6
WRÓBEL ET AL.
(125 MHz, DMSO-d6): δ = 99.2 (d, JFC = 28 Hz), 106.5,
249 (14). HRMS (EI): m/z calcd for C14H9N2F3O [M]+:
112.6 (d, JFC
=
25 Hz), 115.9, 116.5, 120.0 (d,
278.0667; found: 278.0667.
JFC = 10 Hz), 128.3, 133.1, 138.2, 149.0 (d, JFC = 10 Hz),
149.1, 160.2 (d, JFC = 240 Hz), 163.91 (d, JFC = 3 Hz). MS
(EI): m/z (%) = 228 (100, [M]+), 199 (30). HRMS (EI):
m/z calcd for C13H9N2FO [M]+: 228.0699; found: 228.0690.
4.12 | 6-Methyl-5H-dibenzo[b,e][1,4]
diazepin-11(10H)-one (1c); typical
procedure [1]
4.9 | 2-(2-Aminophenyl)benzoxazole-
6-carbonitrile (5c)
In a Schlenk tube, equipped with a teflon plug valve and
a magnetic stirring bar, were placed 2c (544 mg,
2.0 mmol) and PBu3 (10.0 mL). The vessel was tightly
closed, partially immersed in an oil bath placed on a
magnetic stirrer hot plate. The reaction mixture was
stirred at 140ꢀC for 48 h, then the excess of PBu3
was removed at reduced pressure (an oil vacuum pump)
at ca. 100ꢀC and collected in a cold trap. The residue was
then separated on a chromatography column (SiO2,
DCM/MeOH from 50:1 to 10:1).
Yield: 120 mg (26%); pale yellow solid; mp 246–
248ꢀC. FT-IR: 3371, 3178, 3047, 1649, 1471 cmÀ1.1H
NMR (500 MHz, CDCl3): δ = 2.38 (s, 3H), 5.50 (br s, 1H),
6.79–6.83 (m, 2H), 6.89 (t, J = 7.5 Hz, 1H), 6.93 (br d,
J = 7.4 Hz, 1H), 7.01 (ddd, J = 8.0, 7.4, 1.0 Hz, 1H), 7.35
(ddd, J = 8.0, 7.4, 1.7 Hz, 1H), 7.82 (br s, 1H), 7.94 (dd,
J = 8.0, 1.5 Hz, 1H). 13C NMR (125 MHz, CDCl3):
δ = 17.5, 119.6, 119.9, 122.3, 123.3, 123.5, 127.0, 127.4,
129.8, 132.8, 133.6, 138.0, 149.3, 169.0. MS (EI): m/z
(%) = 224 (100, [M]+), 209 (46), 195 (26). HRMS (EI): m/
z calcd for C14H12N2O2 [M]+: 224.0950; found: 224.0951.
Yield: 106 mg (45%); pale yellow solid; mp 209–211ꢀC.
FT-IR: 3358, 3278, 3181, 1621, 1544, 1490, 1246 cmÀ1. 1H
NMR (500 MHz, DMSO-d6): δ = 6.71 (ddd, J = 8.1, 7.0,
1.0 Hz, 1H), 6.94 (d, J = 8.4 Hz, 1H), 7.20 (s, 2H), 7.33
(ddd, J = 8.4, 7.0, 1.4 Hz, 1H), 7.84 (dd, J = 8.4, 1.4 Hz,
1H), 7.90–7.94 (m, 2H), 8.36 (d, J = 1.4 Hz, 1H). 13C
NMR (125 MHz, DMSO-d6): δ = 105.6, 107.0, 115.3,
116.0, 116.8, 119.4, 120.4, 128.8, 129.6, 134.1, 145.7, 148.4,
150.0, 166.1. MS (EI): m/z (%) = 235 (100, [M]+),
206 (21). HRMS (EI): m/z calcd for C14H9N3O [M]+:
235.0746; found: 235.0757.
4.10 | 2-(2-Aminophenyl)-
4-methylbenzoxazole (5d)
Yield: 220 mg (98%); pale beige solid; mp 102–103ꢀC. FT-
IR: 3469, 3337, 1625, 1542, 1435, 1326, 1256 cmÀ1. H
1
NMR (500 MHz, CDCl3): δ = 2.64 (s, 3H), 6.24 (br s, 2H),
6.77–6.84 (m, 2H), 7.14 (d, J = 7.4 Hz, 1H), 7.22
(t, J = 7.8 Hz, 1H), 7.26–7.29 (m, 1H), 7.39 (d, J = 8.0 Hz,
1H), 8.07 (dd, J = 8.0, 1.2 Hz, 1H). 13C NMR (125 MHz,
CDCl3): δ = 16.5, 107.5, 108.9, 116.2, 116.8, 124.3, 124.8,
128.6, 129.8, 132.1, 141.0, 147.6, 148.9, 162.3. MS (EI): m/
z (%) = 224 (100, [M]+), 195 (25). HRMS (EI): m/z calcd
for C14H12N2O [M]+: 224.0950; found: 224.0949.
4.13 | 9-Methyl-5H-dibenzo[b,e][1,4]
diazepin-11(10H)-one (1d)
Obtained from 2d (1088 mg, 4.0 mmol). Yield: 364 mg
(41%); pale yellow crystals; mp 250–252ꢀC (dec.). FT-IR:
3316, 3185, 3031, 1639, 1604, 1467 cmÀ1 1H NMR
.
(500 MHz, CDCl3): δ = 5.41 (br s, 1H), 6.73 (d,
J = 7.6 Hz, 1H), 6.78 (d, J = 8.1 Hz, 1H), 6.86–6.95 (m,
2H), 7.01 (t, J = 7.6 Hz, 1H), 7.31–7.35 (m, 1H), 7.35
(br s, 1H), 7.90 (dd, J = 7.8, 1.5 Hz, 1H). 13C NMR
(125 MHz, CCl3): δ = 18.1, 118.2, 119.1, 122.4, 123.2,
125.2, 125.9, 128.0, 129.2, 132.7, 133.6, 140.2, 149.7, 168.8.
MS (EI): m/z (%) = 224 (100, [M]+), 209 (29), 195 (25).
HRMS (EI): m/z calcd for C14H12N2O [M]+: 224.0950;
found: 224.0950.
4.11 | 2-(2-Aminophenyl)-
(5-trifluoromethyl)benzoxazole (5e)
Yield: 208 mg (74%); colorless crystals; mp 114–115ꢀC.
FT-IR: 3434, 3330, 2228, 1624, 1535, 1429 cmÀ1. 1H NMR
(500 MHz, DMSO-d6): δ = 6.69 (ddd, J = 8.0, 7.0, 1.1 Hz,
1H), 6.92 (dd, J = 8.4, 0.8 Hz, 1H), 7.16 (br s, 2H), 7.30
(ddd, J = 8.4, 7.0, 1.7 Hz, 1H), 7.71 (dd, J = 8.4, 1.7 Hz,
1H), 7.91 (dd, J = 8.0, 1.7 Hz, 1H), 7.93 (d, J = 8.4 Hz,
1H), 8.18 (br s, 1H). 13C NMR (125 MHz, DMSO-d6):
δ = 105.9, 108.7 (q, JFC = 4 Hz), 116.0, 116.7, 120.1, 122.2
(q, JFC = 4 Hz), 124.7 (q, JFC = 272 Hz), 125.6 (q,
JFC = 32 Hz), 128.7, 133.8, 144.9 (q, JFC = 1 Hz), 148.7,
149.8, 165.7. MS (EI): m/z (%) = 278 (100, [M]+),
4.14 | 6-Chloro-5H-dibenzo[b,e][1,4]
diazepin-11(10H)-one (1e)
Obtained from 2e (293 mg, 1.0 mmol). Yield: 146 mg
(60%); colorless crystals; mp 244–246ꢀC. FT-IR: 3343,

WRÓBEL ET AL.
7
3181, 3042, 1643, 1468 cmÀ1. 1H NMR (600 MHz, DMSO-
d6): δ = 6.92–7.00 (m, 3H), 7.12 (dd, J = 8.1, 0.8 Hz, 1H),
7.15 (dd, J = 7.6, 1.7 Hz, 1H), 7.30 (s, 1H), 7.38 (ddd,
J = 8.1, 7.2, 1.7, Hz, 1H), 7.66 (dd, J = 7.6, 1.7 Hz, 1H),
10,10 (s, 1H). 13C NMR (150 MHz, DMSO-d6): δ = 120.9,
121.4, 122.5, 124.2, 124.3, 124.4, 125.3, 132.1, 132.9, 133.6,
136.7, 149.6, 168.2. MS (EI): m/z (%) = 246 (29),
244 (64, [M]+), 209 (100). HRMS (EI): m/z calcd for
C13H935ClN2O4 [M]+: 244.0403; found: 244.0404.
10.21 (br s, 1H). 13C NMR (125 MHz, DMSO-d6):
δ = 103.1, 116.6, 120.8, 122.3, 123.7, 124.0, 126.0, 128.7,
131.9, 132.5, 133.5, 141.3, 148.3, 167.4. MS (EI): m/z
(%) = 235 (100, [M]+), 206 (28), 179 (20). HRMS (EI): m/
z calcd for C14H9N3O [M]+: 235.0746 found: 235.0742.
ACKNOWLEDGMENT
This work was financed by a subvention from the Insti-
tute of Organic Chemistry, Polska Akademia Nauk.
DATA AVAILABILITY STATEMENT
4.15 | 6-Bromo-5H-dibenzo[b,e][1,4]
diazepin-11(10H)-one (1f)
Data available in article supplementary material.
ORCID
Obtained from 2f (1685 mg, 5.0 mmol). Yield: 670 mg
(46%); colorless crystals; mp 242–244ꢀC. FT-IR: 3364,
3180, 3041, 1669, 1476 cmÀ1. 1H NMR (500 MHz, DMSO-
d6): δ = 6.89 (t, J = 8.0 Hz, 1H), 6.98–7.03 (m, 2H), 7.08–
7.12 (m, 2H), 7.31 (dd, J = 7.8, 1.3 Hz, 1H), 7.37–7.42 (m,
1H), 7.67 (dd, J = 7.8, 1.5 Hz, 1H), 10.12 (s, 1H). 13C
NMR (125 MHz, DMSO-d6): δ = 114.8, 121.5, 121.6,
122.7, 124.5, 125.0, 128.5, 132.1, 132.9, 133.6, 137.9, 149.5,
168.2. MS (EI): m/z (%) = 290 (52), 288 (53, [M]+),
209 (100), 154 (22). HRMS (EI): m/z calcd for
C13H979BrN2O [M]+: 287.9898; found: 287.9897.
ꢀ
Zbigniew Wrobel https://orcid.org/0000-0002-9609-7067
REFERENCES
ꢀ
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4.16 | Preparation of 11-oxo-
10,11-dihydro-5H-dibenzo[b,e][1,4]
diazepine-6-carbonitrile (1g)
To
a solution of 1f (289 mg, 1.0 mmol) in N-
[9] L. Chen, L. Ju, K. A. Bustin, J. M. Hoover, Chem. Commun.
2015, 51, 15059.
methylpyrrolidone (15 mL) was added CuCN (108 mg,
1.2 mmol) and the mixture was stirred at 150ꢀC for 48 h.
After cooling, the mixture was poured into aqueous NaCl
solution (100 mL), extracted with EtOAc (3 Â 100 mL).
The combined extracts were washed with water
(3 Â 400 mL) and dried with Na2SO4. After evaporation,
the residue was subjected to column chromatography
(SiO2, toluene/AcOEt 10:1) to isolate 1 g.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
Yield: 40 mg (17%); colorless crystals; mp 282–283ꢀC.
FT-IR: 3328, 3056, 2985, 2225, 1675, 1484 cmÀ1. 1H NMR
(500 MHz, DMSO-d6): δ = 7.02–7.08 (m, 2H), 7.15
(t, J = 7.8 Hz, 1H), 7.30 (dd, J = 7.8, 1.2 Hz, 1H), 7.42–7.
47 (m, 2H), 7.72 (dd, J = 7.8, 1.5 Hz, 1H), 7.93 (br s, 1H),
ꢀ
How to cite this article: Z. Wrobel, B. Wilk,
P. Cmoch, A. Kwast, J Heterocyclic Chem 2021, 1.
https://doi.org/10.1002/jhet.4311