Reductive Condensation of a Nitro Group with Carboxylic Acids Promoted by Phosphorus(III) Compounds: A Short Route to 5 H -Dibenzo[ b, e ][1,4]diazepin-11(10 H)-ones

Article abstract of DOI:10.1055/s-0040-1707347

Tributyl- or triphenylphosphine promotes a one-pot, three-step method for the synthesis of differently substituted dibenzodiazepinones from N -aryl-2-nitroanilines. Pyridine analogues and the corresponding thiazepinones can also be formed using this method. The process involves deoxygenation of the nitro group, then formation of an iminophosphorane intermediate and its intramolecular condensation with a carboxyl group placed in the N -aryl group. The role of the carboxyl group in the formation of the iminophosphorane and the mode of cyclization are discussed.

Full text of DOI:10.1055/s-0040-1707347

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–I
paper
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M. Tryniszewski et al.
Paper
Synthesis
Reductive Condensation of a Nitro Group with Carboxylic Acids
Promoted by Phosphorus(III) Compounds: A Short Route to
5H-Dibenzo[b,e][1,4]diazepin-11(10H)-ones
Michał Tryniszewskia,b
Three Metal-Free Steps in One Operation in One Pot
Robert Bujokb
Roman Gańczarczyka
Zbigniew Wróbel*b
O
H
N
NO2
R
O H
C
2
X2
X1
N
PBu3
X2
X1
N
Y
Z
Z
140–180 °C, 48 h
Y
a Warsaw University of Technology, Faculty of Chemistry, ul.
Noakowskiego 3, 00-664 Warsaw, Poland
b Institute of Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44/52, 00-266 Warsaw, Poland
R
27–83% yield
X = Cl, OMe, CF3, CN, Ph, Me
R = H, Alkyl
Y = CH=CH, N=CH, S
Z = CH, N
zbigniew.wrobel@icho.edu.pl
Received: 26.02.2020
Accepted after revision: 28.05.2020
Published online: 21.07.2020
prior to the concluding cyclization. The alternative ap-
proach, more versatile regarding the assortment of final
products and widely applied for the synthesis of various
dibenzodiazepine derivatives, consists of the synthesis of
the desired tricyclic system in the form of dibenzodiazepin-
11-one. This can be easily transformed into 11-dialkylami-
no or other functionalized derivatives.2–6 Moreover, diben-
zodiazepin-11-ones themselves belong to the most promi-
nent class of dibenzodiazepine derivatives amongst phar-
maceutically important compounds (Figure 1). They exhibit
various biological activities such as neuroleptic,7 antimicro-
bial and antitumor,8 anticancer,6,9 antidepressant,10 antimi-
crobial,11 antiallergic12 and antihistaminic12 activity. Some
of them have been revealed as muscarinic M1-13a,b and M2-
selective13c antagonists or Chk1 kinase inhibitors.14
DOI: 10.1055/s-0040-1707347; Art ID: ss-2020-t0110-op
Abstract Tributyl- or triphenylphosphine promotes a one-pot, three-
step method for the synthesis of differently substituted dibenzodiazepi-
nones from N-aryl-2-nitroanilines. Pyridine analogues and the corre-
sponding thiazepinones can also be formed using this method. The pro-
cess involves deoxygenation of the nitro group, then formation of an
iminophosphorane intermediate and its intramolecular condensation
with a carboxyl group placed in the N-aryl group. The role of the carbox-
yl group in the formation of the iminophosphorane and the mode of cy-
clization are discussed.
Key words cyclocondensation, reduction, nitro compounds, dibenzo-
diazepines, regioselectivity
Recently, we described the intramolecular reductive cy-
clocondensation of a nitro group and an amido group lead-
ing to dibenzodiazepine systems.1 The one-pot reaction,
carried out in an excess of trivalent phosphorus compound,
proceeds via formation of an iminophosphorane intermedi-
ate which subsequently undergoes an aza-Wittig reaction
with the amido group (Scheme 1).
Me2N
Me2N
H
O
N
O
O
N
N
N
N
N
N
N
H
Cl
dibenzepine
tarpane
nevirapine
NR2
N
NO2
NH
PR3
N
HONHOC
PR3
CONR2
Δ
H
O
NH
N
N
CONR2
H
O
N
N
N
N
•2HCl
O
Scheme 1 Reductive cyclization of nitro amides to 11-aminodibenzo-
N
N
diazepines1
pirenzepine
HDAC inhibitor
Figure 1 Examples of bioactive dibenzodiazepin-11-one derivatives
The method directly furnishes dibenzodiazepines such
as clozapine, olanzapine and other 11-dialkylamino-substi-
tuted derivatives because the 11-amino group is introduced
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B
M. Tryniszewski et al.
Paper
Synthesis
Considering the above, we decided to adapt our previ-
ously developed methodology to a simple, one-pot synthe-
sis of dibenzodiazepin-11-ones from easily available nitro-
diarylamine derivatives.
which connection is formed first and, more importantly,
both of these methods are principally nonselective and, in
cases of substituted substrates, can lead to uncertain results
or rather low yields.19a Perhaps the most promising regiose-
lective procedure for path c is that reported lately by Laha et
al.18a but the declared regioselectivity was actually demon-
strated on the one example only.
The modification of our earlier approach to obtain cyclic
11-keto derivatives would require cyclocondensation of the
initially formed iminophosphorane group with a carboxylic
group. Iminophosphoranes, obtained in the Staudinger re-
action of azides and phosphines, react with carboxylic acids
with formation of carboxamides.20 However, the reaction is
known only for aliphatic reactants. Moreover, the synthesis
of cyclic amides by this method was found to be limited to
five-membered lactams.20a Our initial experiments showed
that the proposed approach leading to fused, seven-mem-
bered rings of dibenzodiazepines was operational. When
N-(4-chloro-2-nitrophenyl)anthranilic acid (1a) was heated
at 200 °C for 3 days with an excess of PBu3 (i.e., under the
conditions previously used for cyclization of the amide ana-
logues), dibenzodiazepin-11-one 2a was obtained in 64%
yield (Scheme 3).
For the synthesis of 1,4-dibenzodiazepin-11-ones, dom-
inating and most used are classical approaches. According
to one of them (Scheme 2, path a), the central, seven-mem-
bered amide ring is formed by condensation of a suitable
pair of functions, the amine from one side and a carboxyl-
derived group from the other side of the appropriate diaryl-
amine, by means of various condensing agents and proto-
cols.2–6,14,15 As a rule, the starting materials are prepared by
reducing the nitro group of an appropriate 2-nitrodiaryl-
amine. When catalytic amination of a suitable chlorodiaryl-
amine is used for this purpose, the reaction leads to the cy-
clic product without isolation of the amine intermediate.15
Another popular method for cyclization comprises forma-
tion of a new C–N bond between the arylamine nitrogen
and the other arene ring of the amide by intramolecular
Buchwald–Hartwig coupling (Scheme 2, path b).8b,13b,16,17
This uses CuI or Pd(II) catalysts in the cyclization step and,
as previously, synthesis of the starting amines requires a
separate reduction of a nitro group. This narrows the set of
compatible functional groups, and involves the use of met-
als or other environment-hostile reagents.
O
NO2
COOH
HN
H
N
PBu3
Cl
O
COOR
NO2
H
N
N
H
N
H
200 °C, 3 d
Cl
[H]
X
H2N
X = halogen
1a
2a, 64% yield
COOR
NH2
H
Scheme 3 Model reductive cyclocondensation of 1 to 2
N
COOR
Cl
H
N
The reaction was then optimized to find the best reac-
tion conditions. Similarly to previous findings,21 the most
efficient and convenient phosphorus reagent turned out to
be PBu3 used in an excess at 120–180 °C. Although reactions
with PPh3 achieved comparable yields, PBu3 gave the prod-
uct in high yield at lower temperature, and could be easily
removed from the reaction mixture under reduced pressure
during workup. Phosphorous acid derivatives such as
P(OMe)3 and P(NMe2)3 were found ineffective.
path b
Pd(0)
NH3
path a
O
HN
N
H
path c
path d
one-pot
O
Under the chosen conditions, the cyclization of a series
of nitrodiarylamines 1a–1r carried out at 140 °C for 2 days
one-pot
O
X
Y
NH2
H2N
H2N
yielded
the
expected
1,4-dibenzodiazepin-11-ones
HO
(Scheme 4).
+
+
Hal
NH2
When the yield was unsatisfactory, the reaction was re-
peated at higher temperature. In several instances this re-
sulted in better yields. Scheme 4 shows the yields obtained
at standard temperature 140 °C or at higher temperature,
given in parentheses.
X, Y = leaving groups
Scheme 2 The most popular methods for the synthesis of 1,4-diben-
zodiazepin-11-ones
The reaction seems to be fairly general. It runs equally
well with either electron-withdrawing or electron-donat-
ing substituents placed in either aromatic ring, as well as
for some heterocyclic analogues. A very important feature
Another approach comprises creation of the amine and
the amide linkages in one stage (Scheme 2, paths c and d).
The domino reactions are promoted by Pd catalysts,18a
18b
Cs2CO3
(path c) or Cu (path d).9,19 It is not always clear
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M. Tryniszewski et al.
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Synthesis
moted reaction of 1,2-dichloro-4-(trifluoromethyl)benzene
with 2-aminobenzamide, according to path c in Scheme 2,
although the 1H and 13C NMR spectra of that compound and
2c do not match. Similar discrepancy takes place in the case
of 2a and 2e versus related compounds reported in the
mentioned paper.18b Unfortunately, we could not reproduce
the results presented in that paper. In our hands, the reac-
tion did not provide any dibenzodiazepine derivative.
It is important to note that the reductive cyclization of
nitro acids 1 gave positive results also with tertiary diaryl-
amine derivatives (1i) as well as with their sulfur analogue
(1s). This fact is interesting for mechanistic reasons and
prompted us to take a closer look at this aspect.
PBu3
1
2
140/160/180 °C
O
O
O
HN
HN
HN
F3C
Cl
N
N
H
N
H
H
2a 74%
2b 65%
2c 80%
O
O
O
HN
HN
HN
MeO
N
H
N
H
N
H
Cl
F3C
2d 33%
2e 72%
2f 56% (180 °C)
Contrary to the cyclization of iminophosphoranes with
amido groups,1 the formation of amides from iminophos-
phoranes and carboxylic acids does not follow the aza-Wit-
tig condensation scheme. The widely accepted mechanism
of this process refers to the Staudinger method in which
formation of the intermediate iminophosphorane from the
corresponding azide is rather undoubted (Scheme 5).
O
O
O
HN
HN
HN
Cl
N
N
N
H
H
NC
MeO
2g 77%
2h 66% (180 °C)
2i 31%
O
O
O
HN
HN
HN
CN
Ph
PR3
PR3
– N2
..
N
N
H
Ar N3
Ar
Ar
N
PR3
N
H
N
H
N
Staudinger
Ar COOH
O
2j 38%
2k 83%
O
2l 76%
PR3
– O=PR3
O
O
+
H
HN
HN
HN
PR3
Ar
Ar
N
PR3
Ar NO2
Cadogan
Ar NO
– O=PR3
O–
N
N
N
N
N
N
H
H
H
Cl
O
2m 70%
2n 79%
2o 35%
O
O
HN
HN
F3C
Ar
Ar
Ar NH
PR3
NH
N
S
N
H
N
H
Ar
– O=PR3
2p 27%
2q 45% (160 °C)
O
O
O
O
O
Scheme 5
HN
HN
S
N
H
S
Under the conditions of our reaction, Cadogan deoxy-
genation22 of the nitro group is expected. This process leads
initially to a nitroso group which, after the next deoxygen-
ation, forms a nitrene intermediate. Finally, reaction of the
phosphine with the nitrene gives iminophosphorane, and
also further condensation with a carboxyl function can oc-
cur according to the above-mentioned Staudinger reaction
(Scheme 5).
However, some reservations regarding the above mech-
anistic scheme can be raised. The first step of the deoxygen-
ation is rather obvious, and we found previously that typi-
cal 2-nitrosodiarylamines easily form iminophosphoranes
in the reaction with phosphines.21a Further investigations
revealed that transformation of 2-nitrodiarylamines into
the corresponding iminophosphoranes is possible only
when there is a hydrogen atom at the amine nitrogen
atom.21b This was shown in the reaction of N-methyl-sub-
stituted 2-nitrodiarylamine with triphenylphosphine in
2r 39%
2s 51%
Scheme 4 1,4-Dibenzodiazepin-11-ones 2a–2m and their analogues
2n–2s obtained from the respective nitrodiarylamines 1a–1r or from
the corresponding sulfide 1s
of the presented method is that it allows for unambiguous
synthesis of the desired, differently substituted structures.
This is a remarkable advantage over certain known meth-
ods, such as those shown in Scheme 2 as paths c and d, in
which two C–N bonds are formed consecutively, and in
most cases the intermediate is not recognized. For example,
while the reductive cyclization of 2-{[2-nitro-4-(trifluoro-
methyl)phenyl]amino}benzoic acid (1c) leads definitely to
8-trifluoromethyl-substituted
dibenzodiazepinone
2c
(Scheme 4), we found reported18b that the same structure
was assigned to the compound obtained in the base-pro-
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

D
M. Tryniszewski et al.
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Synthesis
which the iminophosphorane was not formed. Instead,
N-arylbenzimidazole was obtained in low yield, apparently
as a result of the insertion of the intermediate nitrene into a
CH bond of the N-methyl group (Scheme 6).21b
+ PR3
O
O
H
O
O
–
CO2H
N
N
Y
PR3
Y
PR3
1
R3P
R
N
NO2
N
H
N
3
PPh3
R3P=O
Cl
a,b
Cl
R = H
+ PR3
O
+PR3
Cl
PPh3
Cl
PR3
O–
O
–
H
46% yield
NH
CO2
R = Me
a
N
Y
Y
..
N
N
N
Me
4
N
Cl
R3P=O
Cl
b
a
or
Cl
Cl
24% yield
R
R
+ PR3
Scheme 6 Previously reported reaction of N-substituted and N-unsub-
R
stituted nitroanilines with triphenylphosphine21b
P
O
O
O
O
HN
– NH
+PR3
Y
O–
Y
The evident difference in the behavior of N-substituted
and N-unsubstituted nitroanilines in deoxygenation reac-
tions under the action of trivalent phosphorus compounds
has also been reported by others.23 Although the reason for
this phenomenon remains not well recognized, the role of
the hydrogen atom at the amine nitrogen seems to be vital.
For example, in the synthesis of benzimidazoles from ni-
troanilides and triphenylphosphine, a hydrogen bonding
was acknowledged as responsible for stabilization of the ni-
trenoid intermediate that reacts with the phosphine. When
the hydrogen atom is absent, undesired intramolecular re-
actions of the nitrene occur.23a In light of the above, positive
results in the cyclization of 1i and 1s, affording 2i and 2s re-
spectively, call for a reconsideration of the mechanism.
It is very likely that the carboxyl function can take the
place of the N-hydrogen, playing the role of a proton source
in the early step of the process. A supposed mechanistic
scheme based on this suggestion is illustrated in Scheme 7.
After partial deoxygenation of the nitro group, followed by
addition of the phosphine to the nitroso group, protonation
of the negative nitrogen in 3 occurs.24 This prevents forma-
tion of a nitrene and allows the substitution of phosphine
oxide by another phosphine molecule. Since iminophos-
phoranes are more basic than carboxylates,20a the interme-
diate iminophosphorane is formed and stays in zwitterionic
form 4 that is not prone to a proton transfer. Instead, a
transfer of the phosphonium group to the carboxylic oxy-
gen takes place, followed by intramolecular acylation of the
negatively charged nitrogen atom (Scheme 7, path a).
Alternatively, cyclic intermediate 6 is formed, followed
by extrusion of phosphine oxide (Scheme 7, path b).20 This
O
HN
6
5
Y
O
R3P=O
HN
R3P=O
Y
2
Y = NH, NR1, S
Scheme 7
mechanistic scheme should be also valid for the reactions of
N-unsubstituted nitro acids 1 since carboxylic hydrogen is
much more acidic than N-hydrogen of the diarylamine.
Looking for experimental support for the proposed
mechanistic scheme, we attempted to isolate any interme-
diate products. For the reductive cyclization of nitro am-
ides,1 the corresponding iminophosphoranes could be iso-
lated from reactions carried out at lower temperature, then
transformed further into the final dibenzodiazepines. In the
case of nitro acids 1, that approach did not result in success.
The reaction of nitro acid 1e with an excess of PBu3 or PPh3
carried out at 120 or 100 °C led slowly to the cyclic product
2e, and no iminophosphorane was obtained. Apparently,
the last step of the reaction is the fastest one. Unfortunately,
we were also unable to synthesize any corresponding nitro-
so acid by direct25 or by multistep methods. Therefore, we
tried to take a closer look at the crucial step of the supposed
transformation leading to the iminophosphorane interme-
diate, by examining the reaction of nitrosodiarylamine 7
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

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M. Tryniszewski et al.
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Synthesis
with tetraphenyldiphosphinoethane 8 (Scheme 8). In this
case, as the carboxylic function is not present, the diaryl-
amine NH group was expected to be a source of the crucial
proton. Because of the two phosphine groups located in vi-
cinity in 8, the supposed intramolecular substitution of the
phosphine oxide with the other phosphorus group placed
in the same molecule, via a six-membered transition state,
seemed to be the most convenient, thus, the most likely
process.
O
NO2
COOH
HN
Cl
PPh3
2 d, 160 °C
Cl
Cl
+
Cl
Cl
Cl
11 25% yield
Ph3P=O
Scheme 9 Intermolecular variant of the reductive amidation
O
Ph
Ph
Ph
Ph
P
In conclusion, a short, one-pot and regioselective meth-
od for the synthesis of differently substituted dibenzoaze-
pinones and their analogues from N-aryl-2-nitroanilines or
the corresponding sulfides has been presented. Deoxygen-
ation of the nitro group initiates transformations that end
in intramolecular condensation with the nearby carboxyl
group, to form a fused seven-membered ring. The reaction
tolerates various substituents in both aromatic rings, and
proceeds well in the case of pyridine analogues.
Ph
Ph
P
Ph
O
Ph
Ar
N
N
P
HN
Ar
H
H
P
NH
Cl
N
Cl
N
N
8
Ar
Ar
N
+
MeCN, r.t.
Cl
Cl
Cl
Cl
Cl
Cl
10
34%
50%
9
7
17% yield of the reaction of 7 with 8
+
Ph2P
O
PPh2
PPh2
8 = Ph2P
NH
Cl
N–
Ar = 2,6-dimethylphenyl
Melting points were recorded in open capillaries and are uncorrected.
1H and 13C NMR spectra of all compounds studied were measured at
temperature 298 K in CDCl3 or DMSO-d6 solutions with a VNMRS-500
spectrometer using TMS as internal standard. Mass spectra (EI, 70 eV)
were obtained on an AutoSpec Premier (Waters) spectrometer. For
ESI+ and ESI– measurements, a MALDI SYNAPT G2-S HDMS (Waters)
system was used. Accurate mass measurements were obtained using
a magnetic sector mass analyzer (EI) or TOF analyzer (ESI). IR spectra
(KBr) were recorded on an FT/IR Jasco 6200 spectrophotometer. Mer-
ck silica gel 60 (230–400 mesh) was used for column chromatogra-
phy. When required for melting point measurements, analytical sam-
ples of products were recrystallized from a suitable solvent. All com-
mercial reagents were used without additional purification. The
synthesis and characterization data of nitro acids 1 are provided in
the Supporting Information.
Ar
Cl
Scheme 8
The reaction was carried out with a fivefold excess of 8
under the standard reaction conditions. As a result, the ma-
jor compound 9 was obtained as major product in 50%
yield, accompanied by 10 (formally 34% yield), apparently
formed by initial intermolecular condensation of only 17%
of 7 with 8, without participation of the terminal PPh2
group. The final formation of 10 was a result of subsequent
condensation that excludes possibility of the intramolecu-
lar process. The alternative participation of a free nitrene
intermediate would result in formation of the statistically
preferred iminophosphorane bearing an unoxidized termi-
nal phosphorus group. Thus, the reaction course via a ni-
trene intermediate seems to be marginal. The result sup-
ports the mechanism of iminophosphorane formation pro-
posed for nitro acids 1 in which operation of the carboxylic
hydrogen should be much more efficient.
Dibenzodiazepinones 2a–2s; General Procedure
In a Schlenk tube, equipped with a Teflon plug valve and a magnetic
stirrer bar, were placed 1 (0.8 mmol) and PBu3 (2.4 mL). The vessel
was tightly closed, and partially immersed in an oil bath placed on a
heating magnetic stirrer. The reaction mixture was stirred at 140 °C
(at 160 °C or 180 °C in the specified cases) for 48 h then the excess
PBu3 was removed at reduced pressure (oil vacuum pump) at ca.
100 °C, and collected in a cold trap. The residue was then separated
on a chromatography column (silica gel, DCM/MeOH, 50:1 to 10:1).
One could expect that the intramolecular sequence of
reactions presented here can also operate in the case of
separated reactants, i.e. nitroarene and aromatic carboxylic
acids in an intermolecular manner. Indeed, a prototype re-
action of 2,4-dichloronitrobenzene with 3-chlorobenzoic
acid and PPh3, carried out under the typical reaction condi-
tions, provided respective amide 11 (Scheme 9). However,
the yield of this particular reaction was much lower than in
most intramolecular instances.
8-Chloro-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one (2a)
Yield: 144 mg (74%); yellow solid; mp 237–239 °C (Lit.18b 231.2–
232.8 °C).
1H NMR (500 MHz, DMSO-d6):  = 6.89 (ddd, J = 8.1, 7.2, 1.1 Hz, 1 H),
6.95 (dd, J = 8.1, 1.1 Hz, 1 H), 6.97–6.99 (m, 3 H), 7.33 (ddd, J = 8.1, 7.2,
1.7 Hz, 1 H), 7.66 (dd, J = 7.9, 1.7 Hz, 1 H), 7.95 (s, 1 H), 9.89 (s, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 119.1, 120.4, 120.9, 121.0, 122.3,
123.9, 126.2, 131.2, 132.2, 133.5, 138.7, 149.7, 167.6.
MS (EI): m/z (%) = 246 (45), 244 (100, [M]+), 209 (75), 181 (23), 154
(20).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

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M. Tryniszewski et al.
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HRMS (EI): m/z calcd for C13H935ClN2O [M]+: 244.0403; found:
8-Methoxy-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one (2f)
Yield: 108 mg (56%); yellow solid; mp 176–179 °C (Lit.12 174–176 °C).
244.0398.
1H NMR (500 MHz, DMSO-d6):  = 3.64 (s, 3 H), 6.53–6.57 (m, 2 H),
6.82–6.86 (m, 1 H), 6.89 (d, J = 8.4 Hz, 1 H), 6.94 (dd, J = 8.1, 1.0 Hz, 1
H), 7.29 (ddd, J = 8.1, 7.2, 1.7 Hz, 1 H), 7.61 (s, 1 H), 7.64 (dd, J = 7.8, 1.7
Hz, 1 H), 9.75 (s, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 55.2, 106.8, 109.4, 118.8, 120.36,
120.38, 122.6, 130.8, 132.0, 133.1, 133.1, 151.0, 155.3, 168.0.
5H-Dibenzo[b,e][1,4]diazepin-11(10H)-one (2b)
Yield: 109 mg (65%); yellow solid; mp 257–259 °C (Lit.15 255–257 °C).
IR (KBr): 3320, 3171, 3026, 1641, 1605, 1508, 1472, 1394 cm–1
1H NMR (500 MHz, DMSO-d6):  = 6.88–7.02 (m, 6 H), 7.34 (ddd, J =
8.1, 7.0, 1.6 Hz, 1 H), 7.68 (dd, J = 7.8, 1.6 Hz, 1 H), 7.84 (s, 1 H), 9.83 (s,
1 H).
.
MS (EI): m/z (%) = 240 (100, [M]+), 211 (28), 197 (51), 169 (22), 77
13C NMR (125 MHz, DMSO-d6):  = 119.5, 120.2, 121.1, 121.7, 123.2,
(14).
C
14H12N2O2 [M]+: 240.0899; found:
123.4, 124.9, 130.3, 132.5, 133.6, 140.4, 150.9, 168.3.
HRMS (EI): m/z calcd for
MS (EI): m/z (%) = 210 (100, [M]+), 181 (35), 154 (16).
240.0894.
HRMS (EI): m/z calcd for C13H10N2O [M]+: 210.0793; found: 210.0792.
11-Oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepine-7-carboni-
trile (2g)
8-(Trifluoromethyl)-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one
Yield: 145 mg (77%); yellow powder; mp >300 °C.
(2c)
1H NMR (500 MHz, DMSO-d6):  = 6.91 (ddd, J = 7.9, 7.2, 1.2 Hz, 1 H),
6.96 (dd, J = 8.1, 1.2 Hz, 1 H), 7.07 (d, J = 8.8 Hz, 1 H), 7.32–7.38 (m, 3
H), 7.68 (dd, J = 7.9, 1.6 Hz, 1 H), 8.14 (s, 1 H), 10.19 (s, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 106.7, 119.1, 119.7, 121.7, 122.1,
122.6, 123.2, 127.4, 132.7, 134.3, 135.0, 140.2, 149.3, 167.8.
MS (EI): m/z (%) = 235 (100, [M]+), 206 (27), 179 (21).
HRMS (EI): m/z calcd for C14H9N3O [M]+: 235.0746; found: 235.0751.
Obtained by following the general procedure, starting from 1c (326
mg, 1.0 mmol).
Yield: 224 mg (80%); yellow solid; mp 177–180 °C (Lit.12 176–177 °C).
1H NMR (500 MHz, DMSO-d6):  = 6.91 (ddd, J = 7.9, 7.2, 1.2 Hz, 1 H),
6.98 (dd, J = 8.2, 1.2 Hz, 1 H), 7.13 (d, J = 8.2 Hz, 1 H), 7.25–7.29 (m, 2
H), 7.35 (ddd, J = 8.1, 7.2, 1.7 Hz, 1 H), 7.69 (dd, J = 7.9, 1.7 Hz, 1 H),
8.28 (s, 1 H), 9.97 (s, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 117.8 (q, JFC = 4 Hz), 119.2, 120.1,
121.1, 121.3 (q, JFC = 4 Hz), 122.1, 123.0 (q, JFC = 32 Hz), 124.1 (q, JFC
=
7-Methoxy-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one (2h)
Yield: 127 mg (66%); yellow solid; mp 236–237 °C (Lit.12 239–240 °C).
269 Hz), 129.9, 132.2, 133.6, 143.0, 148.7, 167.3.
MS (EI): m/z (%) = 278 (100, [M]+), 249 (20), 209 (30).
1H NMR (500 MHz, DMSO-d6):  = 3.66 (s, 3 H), 6.48 (dd, J = 8.8, 2.7
Hz, 1 H), 6.59 (d, J = 2.7 Hz, 1 H), 6.85 (d, J = 8.8 Hz, 1 H), 6.86–6.89 (m,
1 H), 6.95 (dd, J = 8.0, 1.0 Hz, 1 H), 7.28–7.32 (m, 1 H), 7.64 (dd, J = 8.0,
1.5 Hz, 1 H), 7.77 (s, 1 H), 9.66 (s, 1 H).
HRMS (EI): m/z calcd for
C
14H9F3N2O [M]+: 278.0667; found:
278.0678.
7-(Trifluoromethyl)-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one
13C NMR (125 MHz, DMSO-d6):  = 55.6, 105.6, 108.7, 119.5, 121.3,
(2d)
122.6, 123.4, 123.4, 132.5, 133.4, 141.8, 150.6, 156.9, 168.1.
MS (EI): m/z (%) = 240 (100, [M]+), 210 (23), 197 (39), 169 (14).
Yield: 74 mg (33%); creamy powder; mp 202–203 °C (hexane/EtOAc)
(Lit.15 200–202 °C).
1H NMR (500 MHz, DMSO-d6):  = 6.94 (t, J = 7.4 Hz, 1 H), 6.99 (d, J =
7.7 Hz, 1 H), 7.13 (d, J = 8.2 Hz, 1 H), 7.26 (d, J = 7.7 Hz, 1 H), 7.35–7.40
(m, 2 H), 7.71 (dd, J = 7.7, 1.4 Hz, 1 H), 8.14 (s, 1 H), 10.14 (s, 1 H).
HRMS (EI): m/z calcd for
C
14H12N2O2 [M]+: 240.0899; found:
240.0901.
5-Butyl-8-chloro-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one (2i)
13C NMR (125 MHz, DMSO-d6):  = 116.8 (q, JFC = 4 Hz), 119.6, 120.1
Yield: 75 mg (31%); colorless powder; mp 161–164 °C.
(q, JFC = 4 Hz), 121.6, 122.0, 122.7, 124.5 (q, JFC = 271 Hz), 125.1 (q, JFC
=
IR (KBr): 3185, 3057, 2956, 2868, 1666, 1584, 1496, 1379 cm–1
.
32 Hz), 132.7, 133.9, 134.1, 140.2, 149.7, 167.9.
HRMS (ESI): m/z calcd for C14H9F3N2ONa [M + Na]+: 301.0565; found:
301.0552.
1H NMR (500 MHz, DMSO-d6):  = 0.84 (t, J = 7.3 Hz, 3 H), 1.34 (sext,
J = 7.3 Hz, 2 H), 1.45–1.50 (m, 2 H), 3.63–3.78 (m, 2 H), 7.10–7.18 (m,
3 H), 7.22 (d, J = 8.7 Hz, 2 H), 7.51 (ddd, J = 8.0, 7.2, 1.7 Hz, 1 H), 7.62
(dd, J = 7.8, 1.7 Hz, 1 H), 10.30 (s, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 14.0, 19.8, 29.4, 48.5, 119.5, 121.1,
122.4, 123.6, 124.5, 127.9, 128.4, 131.2, 133.2, 135.4, 142.6, 152.1,
168.7.
MS (EI): m/z (%) = 302 (20), 300 (40, [M]+), 259 (44), 257 (100), 221
(24).
HRMS (EI): m/z calcd for C17H1735ClN2O [M]+: 300.1029; found:
300.1029.
7-Chloro-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one (2e)
Yield: 140 mg (72%); yellow crystals; mp 255–257 °C (Lit.12 253–
254 °C).
IR (KBr): 3338, 3182, 3040, 1640, 1602, 1478, 1390, 1376 cm–1
.
1H NMR (500 MHz, DMSO-d6):  = 6.88–6.96 (m, 4 H), 7.05 (br s, 1 H),
7.34 (ddd, J = 8.1, 7.3, 1.6 Hz, 1 H), 7.66 (dd, J = 7.6, 1.6 Hz, 1 H), 7.95
(s, 1 H), 9.91 (s, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 109.5, 119.09, 119.10, 121.2,
122.5, 122.6, 128.0, 128.9, 132.1, 133.4, 141.1, 149.4, 167.4.
MS (EI): m/z (%) = 244 (91, [M]+), 209 (100), 181 (29), 154 (27).
11-Oxo-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepine-2-carboni-
trile (2j)
C
13H935ClN2O [M]+: 244.0403; found:
Yield: 71 mg (38%); yellow solid; mp >300 °C.
HRMS (EI): m/z calcd for
244.0400.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

G
M. Tryniszewski et al.
Paper
Synthesis
1H NMR (500 MHz, DMSO-d6):  = 6.91–7.01 (m, 4 H), 7.07 (d, J = 8.3
Hz, 1 H), 7.69 (dd, J = 8.6, 2.0 Hz, 1 H), 8.03 (d, J = 2.0 Hz, 1 H), 8.65 (s,
1 H), 10.01 (s, 1 H).
MS (EI): m/z (%) = 247 (46), 245 (100, [M]+), 217 (36), 210 (41), 182
(27).
HRMS (EI): m/z calcd for
C
12H835ClN3O [M]+: 245.0356; found:
13C NMR (125 MHz, DMSO-d6):  = 102.2, 119.2, 120.2, 120.6, 121.8,
245.0358.
121.9, 124.3, 125.2, 129.3, 136.4, 137.2, 137.8, 153.7, 166.3.
MS (EI): m/z (%) = 235 (100, [M]+), 206 (33), 179 (22).
5,11-Dihydro-6H-dipyrido[2,3-e:3′,2′-b][1,4]diazepin-6-one (2o)
HRMS (EI): m/z calcd for C14H9N3O [M]+: 235.0746; found: 235.0755.
Yield: 59 mg (35%); yellow solid; mp 216 °C (dec. before melting).
1H NMR (500 MHz, DMSO-d6):  = 6.23 (s, 2 H), 6.86 (dd, J = 7.3, 1.2
Hz, 1 H), 7.00 (t, J = 7.3 Hz, 1 H), 7.49 (dd, J = 7.9, 4.4 Hz, 1 H), 8.18 (dd,
J = 7.3, 1.2 Hz, 1 H), 8.66 (dd, J = 7.9, 2.1 Hz, 1 H), 9.05 (dd, J = 4.4, 2.1
Hz, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 109.0, 110.7, 113.6, 115.5, 120.8,
137.0, 141.9, 143.0, 156.2, 157.6, 159.9.
7-Phenyl-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one (2k)
Yield: 190 mg (83%); colorless solid; mp 204–206 °C.
IR (KBr): 3322, 3174, 3025, 1645, 1599, 1469, 1377 cm–1
.
1H NMR (500 MHz, DMSO-d6):  = 6.89 (ddd, J = 8.0, 7.2, 1.2 Hz, 1 H),
6.99 (dd, J = 8.1, 1.0 Hz, 1 H), 7.02 (d, J = 8.2 Hz, 1 H), 7.18 (dd, J = 8.2,
2.0 Hz, 1 H), 7.29–7.35 (m, 3 H), 7.40–7.45 (m, 2 H), 7.53–7.56 (m, 2
H), 7.68 (dd, J = 7.8, 1.6 Hz, 1 H), 7.91 (s, 1 H), 9.91 (s, 1 H).
HRMS (ESI): m/z calcd for C11H9N4O [M + H]+: 213.0776; found:
213.0768.
13C NMR (125 MHz, DMSO-d6):  = 118.3, 119.5, 121.2, 121.6, 122.1,
123.1, 126.6, 127.7, 129.4, 129.6, 132.6, 133.7, 136.9, 139.8, 140.6,
150.5, 168.2.
MS (EI): m/z (%) = 286 (100, [M]+), 257 (21).
HRMS (EI): m/z calcd for C19H14N2O [M]+: 286.1106; found: 286.1103.
6,11-Dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-5-one (2p)
Yield: 46 mg (27%); yellow solid; mp 293–295 °C (Lit.26 283–287 °C).
IR (KBr): 3235, 3195, 2958, 2925, 2855, 1649, 1518, 1442, 1296, 1138,
1090 cm–1
.
1H NMR (500 MHz, DMSO-d6):  = 6.91–6.99 (m, 4 H), 7.13 (d, J = 7.1
Hz, 1 H), 8.06 (dd, J = 7.7, 1.8 Hz, 1 H), 8.25 (dd, J = 4.6, 1.9 Hz, 1 H),
8.66 (s, 1 H), 9.96 (s, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 116.1, 117.1, 120.9, 121.8, 123.8,
125.1, 129.2, 136.5, 142.1, 152.5, 159.6, 167.0.
MS (EI): m/z (%) = 211 (100, [M]+), 183 (22).
HRMS (EI): m/z calcd for C12H9N3O [M]+: 211.0746; found: 211.0745.
7-Morpholin-4-yl-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one (2l)
Yield: 180 mg (76%); yellow crystals; mp 263–265 °C.
IR (KBr): 3319, 3160, 2958, 2867, 2808, 1641, 1600, 1471, 1395, 1236,
1117 cm–1
.
1H NMR (500 MHz, DMSO-d6):  = 2.95–2.99 (m, 4 H), 3.68–3.72 (m, 4
H), 6.51 (dd, J = 8.6, 2.6 Hz, 1 H), 6.57 (d, J = 2.6 Hz, 1 H), 6.80 (d, J = 8.6
Hz, 1 H), 6.86 (ddd, J = 8.2, 7.2, 1.2 Hz, 1 H), 6.93 (dd, J = 8.1, 0.9 Hz, 1
H), 7.29 (ddd, J = 8.1, 7.2, 1.6 Hz, 1 H), 7.63 (dd, J = 7.8, 1.6 Hz, 1 H),
7.66 (s, 1 H), 9.61 (s, 1 H).
2-Methyl-7-(trifluoromethyl)-10H-thieno[2,3-b][1,5]benzodiaze-
pin-4(5H)-one (2q)
13C NMR (125 MHz, DMSO-d6):  = 49.3, 66.5, 106.8, 110.7, 119.4,
Yield: 107 mg (45%); brown solid; mp 178–179 °C.
1H NMR (500 MHz, DMSO-d6):  = 2.50 (d, J = 1.1 Hz, 3 H), 6.84–6.86
(m, 1 H), 7.09 (d, J = 3.6 Hz, 1 H), 7.24 (d, J = 8.3 Hz, 1 H), 7.32 (d, J = 1.7
Hz, 1 H), 7.41 (dd, J = 8.3, 1.7 Hz, 1 H), 11.60 (br s, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 15.6, 106.2 (q, JFC = 4 Hz), 109.2,
119.0 (q, JFC = 4 Hz), 125.0 (q, JFC = 122 Hz), 123.1 (q, JFC = 32 Hz), 124.3,
124.4, 129.1, 131.6, 133.8, 138.4, 153.5.
121.1, 122.3, 122.4, 123.4, 132.4, 133.3, 141.2, 148.9, 150.7, 168.1.
MS (EI): m/z (%) = 295 (100, [M]+), 237 (37), 209 (37), 181 (11).
HRMS (EI): m/z calcd for
C
17H17N3O2 [M]+: 295.1321; found:
295.1332.
8-Methyl-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one (2m)
Yield: 125 mg (70%); yellow solid; mp 200–204 °C (Lit.12 194–195 °C).
MS (EI): m/z (%) = 298 (100, [M]+), 237 (20), 97 (29).
HRMS (EI): m/z calcd for
C
13H9F3N2OS [M]+: 298.0388; found:
IR (KBr): 3380, 3174, 3028, 1656, 1602, 1518, 1466, 1390 cm–1
.
298.0389.
1H NMR (500 MHz, DMSO-d6):  = 2.17 (s, 3 H), 6.73–6.78 (m, 2 H),
6.84–6.89 (m, 2 H), 6.96 (dd, J = 8.1, 1.0 Hz, 1 H), 7.31 (ddd, J = 8.1, 7.3,
1.8 Hz, 1 H), 7.66 (dd, J = 7.8, 1.6 Hz, 1 H), 7.72 (s, 1 H), 9.76 (s, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 20.1, 118.9, 119.6, 120.5, 121.5,
122.7, 124.9, 129.6, 131.9, 132.0, 133.1, 137.4, 150.7, 168.0.
MS (EI): m/z (%) = 224 (100, [M]+), 209 (27), 195 (29), 181 (14).
HRMS (EI): m/z calcd for C14H12N2O [M]+: 224.0950; found: 224.0957.
2-Methyl-10H-thieno[2,3-b][1,5]benzodiazepin-4(5H)-one (2r)
Yield: 72 mg (39%); brown solid; mp 161–163 °C.
1H NMR (500 MHz, CDCl3):  = 2.53 (d, J = 1.3 Hz, 3 H), 6.74–6.77 (dq,
J = 3.7, 1.3 Hz, 1 H), 6.99 (d, J = 3.7 Hz, 1 H), 7.05–7.15 (m, 4 H), 10.18
(br s, 1 H).
13C NMR (125 MHz, CDCl3):  = 15.7, 109.2, 110.0, 121.7, 122.6, 123.8,
124.5, 127.8, 131.2, 131.7, 138.9, 154.9.
MS (EI): m/z (%) = 230 (100, [M]+), 201 (19), 169 (22).
9-Chloro-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-5-one
(2n)
HRMS (EI): m/z calcd for
C
12H10N2OS [M]+: 230.0514; found:
Yield: 155 mg (79%); yellow powder; mp >300 °C.
230.0517.
1H NMR (500 MHz, DMSO-d6):  = 6.95–7.00 (m, 3 H), 7.21 (d, J = 2.0
Hz, 1 H), 8.08 (dd, J = 7.8, 2.0 Hz, 1 H), 8.27 (dd, J = 4.6, 1.7 Hz, 1 H),
8.83 (s, 1 H), 10.05 (s, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 116.0, 117.5, 120.1, 123.0, 123.3,
128.2, 128.7, 137.7, 142.2, 152.6, 158.7, 166.5.
Dibenzo[b,f][1,4]thiazepin-11(10H)-one (2s)
Yield: 93 mg (51%); colorless solid; mp 257–258 °C (Lit.27 263–
265 °C).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

H
M. Tryniszewski et al.
Paper
Synthesis
IR (KBr): 3171, 3040, 2955, 1647, 1581, 1477, 1376 cm–1
.
MS (EI): m/z (%) = 301 (15), 299 (15, [M]+), 266 (14), 264 (22), 141
(50), 139 (100), 111 (58).
1H NMR (500 MHz, DMSO-d6):  = 7.12 (td, J = 7.5, 1.5 Hz, 1 H), 7.21
(dd, J = 8.0, 1.0 Hz, 1 H), 7.32–7.36 (m, 1 H), 7.42 (td, J = 7.5, 1.5 Hz, 1
H), 7.46 (td, J = 7.5, 1.5 Hz, 1 H), 7.51 (dd, J = 7.5, 1.5 Hz, 1 H), 7.54 (dd,
J = 8.0, 1.0 Hz, 1 H), 7.66 (dd, J = 7.5, 1.5 Hz, 1 H), 10.68 (s, 1 H).
HRMS (EI): m/z calcd for
298.9677.
C
13H835Cl3NO [M]+: 298.9671; found:
13C NMR (125 MHz, DMSO-d6):  = 123.6, 125.9, 129.4, 129.4, 130.3,
131.7, 131.8, 132.5, 133.0, 136.7, 138.3, 140.4, 168.8.
Supporting Information
MS (EI): m/z (%) = 227 (100, [M]+), 195 (40), 167 (27).
HRMS (EI): m/z calcd for C13H9NOS [M]+: 227.0405; found: 227.0403.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1707347.
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Reaction of 2-Nitrosodiarylamine 7 with Excess Diphosphine 8
References
[2-(Diphenylphosphino)ethyl](diphenyl)phosphine (8) (1494 mg,
3.75 mmol) was suspended in MeCN (19 mL), and N-(3,5-dichloro-2-
nitrosophenyl)-N-(2,6-dimethylphenyl)amine (7) (221 mg, 0.75
mmol) was added in a few portions. The mixture was stirred for 3 d at
room temperature then the solvent was removed in vacuo. The resi-
due was separated by column chromatography (silica gel, hex-
ane/DCM, 1:1, then hexane/EtOAc, 2:1) to obtain 9 (262 mg, 50%
yield) and 10 (122 mg, 34% yield).
(1) Tryniszewski, M.; Bujok, R.; Cmoch, P.; Gańczarczyk, R.;
Kulszewicz-Bajer, I.; Wróbel, Z. J. Org. Chem. 2019, 84, 2277.
(2) Joshua, A. V.; Sharma, S. K.; Strelkov, A.; Scott, J. R.; Martin-Iver-
son, M. T.; Abrams, D. N.; Silverstone, P. H.; McEwan, A. J. B.
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N-(3,5-Dichloro-2-{[[2-(diphenylphosphoryl)ethyl](diphe-
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nyl)amine (9)
Yield: 262 mg (50%); pale beige solid; mp 95–98 °C.
(6) Yu, Y.; Wu, J.; Lei, F.; Chen, L.; Wan, W.; Hai, L.; Guan, M.; Wu, Y.
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Chandrasekhar, S.; Hügel, H. M. Eur. J. Med. Chem. 2016, 108,
674.
1H NMR (500 MHz, CDCl3):  = 1.97 (s, 6 H), 2.41–2.49 (m, 2 H), 2.75–
2.84 (m, 2 H), 5.86 (t, J = 2.0 Hz, 1 H), 6.25 (s, 1 H), 6.64 (dd, J = 2.6, 0.5
Hz, 1 H), 7.03–7.07 (m, 3 H), 7.37–7.44 (m, 7 H), 7.46–7.51 (m, 4 H),
7.55–7.60 (m, 4 H), 7.74–7.78 (m, 4 H).
13C NMR (125 MHz, CDCl3):  = 18.2, 21.7 (dd, JPC = 20.8, 3.3 Hz), 22.2
(dd, JPC = 16.2, 3.5 Hz), 108.1, 117.3 (d, JPC = 2.0 Hz), 124.1 (d, JPC = 2.9
Hz), 125.7, 126.8 (d, JPC = 7.5 Hz), 128.5, 128.8 (dd, JPC = 12.0, 4.5 Hz),
130.6 (d, JPC = 9.3 Hz), 131.1 (d, JPC = 9.3 Hz), 131.4 (d, JPC = 8.7 Hz),
131.9 (dd, JPC = 21.9, 2.9 Hz), 132.2 (d, JPC = 5.2 Hz), 132.5 (d, JPC = 1.6
Hz), 135.3, 138.3, 143.6 (d, JPC = 10.4 Hz).
MS (EI): m/z (%) = 694 (41), 692 (57, [M]+), 493 (67), 491 (97), 207
(100).
HRMS (EI): m/z calcd for C40H3635Cl2N2OP2 [M]+: 692.1680; found:
(10) Lehner, H.; Gauch, R.; Michaelis, W. Arzneim.-Forsch. 1967, 17,
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692.1671.
(12) Hunziker, F.; Lauener, H.; Schmutz, H. Arzneim.-Forsch. 1963,
13, 324.
Compound 10
Yield: 122 mg (34%); colorless solid; mp 250–253 °C (dec.).
(13) (a) Giachetti, A.; Giraldo, E.; Ladinsky, H.; Montagna, E. Br.
J. Pharmacol. 1986, 89, 83. (b) Tahtaoui, C.; Parrot, I.; Klotz, P.;
Guillier, F.; Galzi, J.-L.; Hibert, M.; Ilien, B. J. Med. Chem. 2004,
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(14) (a) Hasvold, L. A.; Wang, L.; Przytulińska, M.; Xiao, Z.; Chen, Z.;
Gu, W.-Z.; Merta, P. J.; Xue, J.; Kovar, P.; Zhang, H.; Park, C.;
Sowin, T. J.; Rosenberg, S. H.; Lin, N.-H. Bioorg. Med. Chem. Lett.
2008, 18, 2311. (b) Wang, L.; Sullivan, G. M.; Hexamer, L. A.;
Hasvold, L. A.; Thalji, R.; Przytulinska, M.; Tao, Z. F.; Li, G.; Chen,
Z.; Xiao, Z.; Gu, W. Z.; Xue, J.; Bui, M. H.; Merta, P.; Kovar, P.;
Bouska, J. J.; Zhang, H.; Park, C.; Stewart, K. D.; Sham, H. L.;
Sowin, T. J.; Rosenberg, S. H.; Lin, N. H. J. Med. Chem. 2007, 50,
4162.
1H NMR (500 MHz, CDCl3):  = 1.99 (s, 12 H), 2.76–2.78 (m, 4 H),
5.81–5.83 (m, 2 H), 6.28 (s, 2 H), 6.53 (d, J = 2.5 Hz, 2 H), 7.03–7.08 (m,
6 H), 7.35–7.40 (m, 8 H), 7.44–7.49 (m, 4 H), 7.63–7.68 (m, 8 H).
13C NMR (125 MHz, CDCl3): sample not pure enough.
MS (EI): m/z (%) = 956 (6), 954 (4, [M]+), 493 (67), 491 (100).
HRMS (ESI): m/z calcd for C54H4935Cl4N4P2 [M + H]+: 955.2187; found:
955.2177.
3-Chloro-N-(2,4-dichlorophenyl)benzamide (11)
Yield: 59 mg (25%); colorless solid; mp 140–142 °C.
1H NMR (500 MHz, CDCl3):  = 7.32 (dd, J = 6.6, 2.4 Hz, 1 H), 7.44 (d, J =
2.4 Hz, 1 H), 7.47 (t, J = 7.8 Hz, 1 H), 7.55–7.58 (m, 1 H), 7.76 (d, J = 7.8
Hz, 1 H), 7.88–7.90 (m, 1 H), 8.30 (br s, 1 H), 8.49 (d, J = 9.0 Hz, 1 H).
13C NMR (125 MHz, CDCl3):  = 122.3, 123.6, 124.9, 127.6, 128.1,
128.8, 129.6, 130.3, 132.4, 133.1, 135.3, 136.0, 163.8.
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2005, 61, 61.
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I