N -Acylbenzotriazoles as Proficient Substrates for an Easy Access to Ureas, Acylureas, Carbamates, and Thiocarbamates via Curtius Rearrangement Using Diphenylphosphoryl Azide (DPPA) as Azide Donor

Article abstract of DOI:10.1055/a-1399-3823

A diverse range of ureas, N -acylureas, carbamates, and thiocarbamates has been synthesized in good to excellent yields by reacting N -acylbenzotriazoles individually with amines or amides or phenols or thiols in the presence of diphenylphosphoryl azide (DPPA) as a suitable azide donor in anhydrous toluene at 110 °C for 3-4 hours. In this route, DPPA was found to be a good alternative to trimethylsilyl azide and sodium azide for the azide donor in Curtius degradation. The high reaction yields, one-pot and metal-free conditions, straightforward nature, easy handling, use of readily available reagents, and in many cases avoidance of column chromatography are the notable features of the devised protocol.

Full text of DOI:10.1055/a-1399-3823

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–I
paper
A
en
M. S. Yadav et al.
Paper
Synthesis
N-Acylbenzotriazoles as Proficient Substrates for an Easy Access
to Ureas, Acylureas, Carbamates, and Thiocarbamates via Curtius
Rearrangement Using Diphenylphosphoryl Azide (DPPA) as Azide
Donor
Mangal S. Yadav
O
Sumt K. Singh
N
R1
O
XH
N
Anand K. Agrahari
Anoop S. Singh
N
R2
NH2
R3
(X = S, O, NH)
Vinod K. Tiwari*
0
0
0
0-0
0
0
1
-9
2
4
4
-
8
8
8
9
DPPA
Et3N
Department of Chemistry, Institute of Science, Banaras Hindu
University, Varanasi, 221005, India
tiwari_chem@yahoo.co.in
toluene
R3
H
H
N
H
N
One-pot
Metal-free
Easy handling
Cost-effective
N
X
Vinod.Tiwari@bhu.ac.in
R1
R2
R1
O
O
O
This manuscript is dedicated to the late Prof. Alan R. Katritzky
for his notable contributions to benzotriazole chemistry.
15 examples
Yield: up to 96%
15 examples
Yield: up to 95%
Corresponding Author
Received: 13.01.2021
Accepted after revision: 24.02.2021
Published online: 24.02.2021
H
O
N
Cl
HN
F3C
Cl
NH
O
N
F
DOI: 10.1055/a-1399-3823; Art ID: ss-2021-t0015-op
HN
O
O
O
Abstract A diverse range of ureas, N-acylureas, carbamates, and
thiocarbamates has been synthesized in good to excellent yields by re-
acting N-acylbenzotriazoles individually with amines or amides or phe-
nols or thiols in the presence of diphenylphosphoryl azide (DPPA) as a
suitable azide donor in anhydrous toluene at 110 °C for 3–4 hours. In
this route, DPPA was found to be a good alternative to trimethylsilyl
azide and sodium azide for the azide donor in Curtius degradation. The
high reaction yields, one-pot and metal-free conditions, straightfor-
ward nature, easy handling, use of readily available reagents, and in
many cases avoidance of column chromatography are the notable fea-
tures of the devised protocol.
F
HN
sorafenib
diflubenzuron
CF3
O
H
NH
N
Cl
F
N
H
HN
N
O
HN
O
O
F
Cl
Cl
F
flufenoxuron
cariprazine
F
OCF3
CF3
Cl
HN
F
F
F
F
F
O
F
F
F
F
O
Key words N-acylbenzotriazoles, N-acylureas, benzotriazoles, Curtius
rearrangement, diphenylphosphoryl azide, carbamates, thiocarba-
mates, ureas
HN
HN
HN
Cl
O
Cl
O
O
O
novaluron
lufenuron
Figure 1 Structures of some biologically potent ureas and acylureas
Urea and its derivatives are fascinating candidates for
drug design in medicinal chemistry due to their unique
characteristics, i.e. H-bonding capability with biomolecular
targets.1,2 Many approved drugs to cure various frontline
diseases contain urea as the core moiety,2 including
sorafenib (antineoplastic agent),3 Hetrazan (antihelmin-
thic),4 and cariprazine (anti-psychotic)5 (Figure 1). Acyl-
ureas, the close derivatives of urea, are depicted in a pletho-
ra of applications in the agrochemical field, including the
insect growth regulators diflubenzuron,6 flufenoxuron,7
lufenuron,8 and Novaluron9 (Figure 1). Moreover, a number
of N-acylureas are well-known human liver glycogen phos-
phorylase inhibitors and some of them can be used for the
successful treatment of type 2 diabetes.10
In addition to the widespread applications in drug dis-
covery and development, the urea functionality has been
well explored as an interesting synthetic auxiliary in organ-
ic synthesis for various other purposes.1 Therefore, there is
an increased demand for urea and its derivatives for their
complete chemical, biochemical, and pharmacological in-
vestigation. A variety of synthetic approaches have been
put forward for the facile synthesis of urea derivatives,
mostly by the use of toxic phosgene or triphosgene
(Scheme 1a)11 or an iodine–DMSO reagent system.12 To cir-
cumvent the toxicity issue, several alternate methods using
carbonates13 or Pd/C-catalyzed reaction of an aryl halide
with sodium azide have also been illustrated to synthesize
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
M. S. Yadav et al.
Paper
Synthesis
ureas and their derivatives (Scheme 1b).14a Alternatively,
the synthesis of N-acylureas can be achieved in good yields
by using carbon monoxide (as carbonyl source)/palladium
acetate (Scheme 1c)14b or the carbon monoxide involved re-
action of aryl halide with substituted urea in the presence
of a transition-metal catalyst.15 Previously, our group has
devised a synthetic method for carbamates, thiocarba-
mates, and symmetric ureas from N-acylbenzotriazoles via
Curtius rearrangement.16a Although, this method has an is-
sue, particularly for the synthesis of unsymmetrical ureas.
Thus, we further extended the protocol by reacting N-acyl-
benzotriazoles with amine and TMSN3 in the presence of
Et3N as base in anhydrous toluene at 110 °C to furnish high
yields of required unsymmetrical ureas and their deriva-
tives.16b,c
To overcome these major issues, we have devised a nov-
el one-pot route for the synthesis of a series of symmetric
urea, unsymmetric urea, acylurea, carbamate, and thiocar-
bamate derivatives using N-acylbenzotriazoles as model
substrates and diphenylphosphoryl azide (DPPA) as azide
donor, which we envisage to report herein. The reaction
proceeds through in situ generation of N-acyl azide, which
on heating is subsequently converted into an isocyanate in-
termediate via Curtius rearrangement and finally trapped
with various nucleophiles like amines, amides, phenols, and
thiophenols to afford the respective ureas, N-acylureas, car-
bamates, and thiocarbamates as sole products (Scheme 1).
Our synthesis commenced with the construction of N-
acylbenzotriazoles 1a–q, which were obtained from the re-
spective carboxylic acids under a standard known protocol.
N-Acylbenzotriazoles are generally solid, stable to moisture
at room temperature, excellent substitutes for acid chlo-
rides, and the most relevant substrate extensively used as
an acylating agent in acylation reactions.22 It is evident
from the literature that a wide variety of devised protocols
are available to synthesize N-acylbenzotriazoles, which
mainly include the reaction of carboxylic acid with I2/PPh3
or SOCl2 or NBS/PPh3 or PySSPy and 1H-benzotriazole in an-
hydrous dichloromethane (Scheme 2).23–25
Previous work:
R3 R4
O
COCl2
(a)
(b)
(c)
O
R1
R1
N
H
R3
R1
or CO(OCCl3)2
traditional approach
[Ref. 11]
N
R2
Ar
N
R2
N
N
R2
Cl
R4
O
H
H
C
I
N
N
N
Pd/C, CHCl3, KOH
[Ref. 14a]
R
NH2
R
NaN3
O
CO
O
O
O
O
1,10-phenanthroline
R2
XH
R2
O
Method A: BtH, SOCl2, DCM, rt [Ref. 24a]
O
Method
A/B/C
R1
N
X
R1
R1
N C O
N3
Pd(OAc)2
[Ref. 14b]
H
N
N
Method B: BtH, PySSPy, DCM, rt [Ref. 24b]
Method C: BtH, TCICA, DCM, rt [Ref. 25b]
OH
(X = NH, O)
N
1a–q
This work:
O
H
H
R1
O
O
O
O
R1 NH2
N
N
F
Br
R
N
N
O
N
N
N
N
N
N
O
O
O
C
N
N
N
N
N
acylureas
DPPA
Cl
N
base
1a (92%)A
1b (80%)B
1c (80%)A
R
R
1d (65%)B
N
N
H
BtH
N
X
in situ generated
R1
R1 XH
(X = NH, O, S)
O
N
O
N
O
O
isocyanate
R
O
Br
F3C
N
N
N
N
(X = NH, O, S)
N
N
N
N
N
N
Br
1g (84%)A
1h (82%)A
1f (58%)C
Scheme 1 Common approaches for the synthesis of urea and N-acyl-
1e (80%)A
urea derivatives
O
N
O
N
O
N
O
N
N
N
N
N
N
F
N
N
N
Br
Cl
I
In addition to this, thiocarbamates are biologically rele-
vant compounds, particularly known for their antiviral,
bactericidal, pesticidal, and herbicidal activities.17 Thus, dif-
ferent approaches have been developed for their practical
synthesis. The common methods include the reaction of
amines with phosgene18 or the reaction of gaseous carbonyl
sulfide with amines followed by alkylation,19 or iodine-cat-
alyzed reaction with sodium sulfinates,20 or with sulfonyl
chlorides,21a and finally, selenium-based synthesis with the
use of carbon monoxide as carbonyl source.21b However, all
above-mentioned procedures still have some limitations,
particularly in terms of sensitivity, toxicity, high cost, use of
transition-metal-based catalysts, and highly explosive na-
ture of reagents involved.
1i (88%)A
1l (67%)C
1j (71%)C
1k (83%)A
O
N
O
N
N
N
N
N
N
N
N
O
O
O
1m (78%)B
1n (59%)A
1o (70%)A
O
O
N
N
N
N
N
N
1q (81%)B
1p (70%)C
Scheme 2 N-Acylbenzotriazoles 1a–q required for the synthesis of
diverse ureas, acylureas, carbamates, and thiocarbamates
Apart from this, benzotriazoles have several advantages,
as they act as a cation stabilizer and anion generator; fur-
ther, they are found to be sufficiently stable during the
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

C
M. S. Yadav et al.
Paper
Synthesis
course of a reaction and, at the end, can be easily eliminated
as well due to their good leaving group tendency. Owing to
these notable features, acylbenzotriazoles have been widely
explored for their diverse applications in chemistry and bi-
ology.26
In this investigation, (1H-benzo[d][1,2,3]triazol-1-
yl)(phenyl)methanone (1a) with DPPA was chosen as the
model substrate which was refluxed at 110 °C to generate
the corresponding isocyanate as functional intermediate.
Furthermore, this intermediate was trapped in situ by se-
lective nucleophiles like amine, amide, thiol, and phenol
derivatives to give the corresponding ureas, acylureas, thio-
carbamates, and carbamates.
Initially, we took 1.0 equivalent of substrate 1a, DPPA
(1.0 equiv.), benzamide (1.0 equiv.), and Et3N (1.0 equiv.) in
anhydrous toluene at 110 °C; then, the reaction mixture
was stirred for 2 hours which afforded compound 2a in 71%
yield (Table 1, entry 2). After achieving the target com-
pound, the reaction was further optimized by varying other
parameters, like solvent, equivalents of reactants, tempera-
ture, and amount of base used. Primarily, we optimized the
reaction in different solvents like DMF, DMSO, THF, toluene,
and chloroform; among them, toluene was found to be the
most appropriate solvent for the reaction (Table 1, entry
11). Further, the reaction was carried out in the absence of
solvent by increasing the equivalents of base (4.0 equiv.);
the yield of compound 2a was drastically reduced to only
24% (Table 1, entry 4), which inferred that the solvent was
necessary for the reaction to proceed. In this continuation,
we also checked the reaction without base and observed
that there was a substantial decrease in the yield (only 15%)
of compound 2a (Table 1, entry 5).
After that, we investigated the effect of temperature on
reaction yield; in this regard, when the temperature was
raised to 140 °C, a slight decrease in yield was observed (Ta-
ble 1, entry 17), while upon lowering the temperature, a
substantial decrease in yield was noticed (Table 1, entries
15 and 16). Towards this optimization, the best result was
obtained when compound 1a (1.0 equiv.) was treated with
DPPA (1.1 equiv.), Et3N (2.0 equiv.), and benzamide (1.0
equiv.) at 110 °C in anhydrous toluene for 3 hours (Table 1,
entry 11).
Table 1 Reaction Optimization Study for N-Acylurea Synthesis via the
Curtius Rearrangement
O
O
O
P
H
N
H
N
O
N3
DPPA
N
N
O
O
benzamide, Et3N
solvent
N
1a
2a
BtH
Entrya DPPA
Et3N
(equiv.)
Solventb
Time
(h)
Temp
(°C)
Yield
(%)c
(equiv.)
1
2
1.0
1.0
1.0
1.0
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.2
1.1
1.1
1.1
1.1
1.1
2.0
1.0
0
toluene
toluene
toluene
–
1.0
2.0
2.0
2.0
2.0
3.0
3.0
3.0
3.0
2–3
3.0
3.0
0.5
0.2
3.0
3.0
3.0
110
110
110
110
110
110
110
110
110
110
110
110
110
110
50
85
71
10
24
15
65
55
54
40
3
4
4.0
0
5
toluene
DCM
6
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
7
DMSO
CHCl3
8
9
THF
10
11
12
13
14
15
16
17
DMF
trace
toluene
toluene
toluene
toluene
toluene
toluene
toluene
93
92
80
30
trace
30
80
140
82
a Reactions were carried out in a sealed tube at 110 °C, unless otherwise
noted.
b Anhydrous solvents were used.
c Yields after column chromatography (silica gel).
chain aliphatic group furnished compound 2o in 67% yield
(Scheme 4). Unfortunately, 1-(1H-benzo[d][1,2,3]triazol-1-
yl)-2-phenylethane-1,2-dione (1n) and 1-(1H-benzo[d]-
[1,2,3]triazol-1-yl)-3-phenylprop-2-yn-1-one (1o) under
the similar optimized conditions could not give the desired
products. Although, by adopting the set protocol, there was
not much fluctuation in the yield of targeted products 2.
To prove the effectiveness and usefulness of this meth-
odology further, we applied the above-optimized reaction
conditions for the synthesis of symmetric and asymmetric
urea derivatives 3a–j. Thus, the reaction of N-acylbenzotri-
azoles 1 with diverse amines (1.0 equiv.) in the presence of
DPPA (1.1 equiv.) and Et3N (2.0 equiv.) in refluxing toluene
for 30 minutes to 5 hours resulted in moderate to good
yields of the target ureas 3a–j (Scheme 5).
After the optimization, the set protocol was put forward
to construct libraries of N-acylurea derivatives 2a–m
through incorporating different substitution on the aromat-
ic ring of N-acylbenzotriazoles and benzamides (Scheme 3).
The structures of the developed compounds were well elu-
1
cidated by extensive spectral analysis, including H NMR,
13C NMR, and mass spectroscopy.
Furthermore, the optimized protocol was checked with
aliphatic N-acylbenzotriazole 1p having an adamantyl
group which resulted in the formation of compound 2n in
80% yield, whereas a similar reaction of 1-(1H-ben-
zo[d][1,2,3]triazol-1-yl)dodecan-1-one (1q) having a long-
Moreover, this methodology was further exploited for
the synthesis of thiocarbamate derivatives. The reaction of
N-acylbenzotriazole derivatives, when carried out with
thiophenols under the optimized conditions, afforded
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

D
M. S. Yadav et al.
Paper
Synthesis
O
O
H
H
N
N
NH2
DPPA, Et3N
O
O
P
R1
R2
O
R2
+
N
N
R1
O
O
R1
O
N3
DPPA
R
110 °C, 0.5–5 h
N
N
N
3a–j
N
N
R
1
H
H
N
benzamides
Et3N, anhyd toluene
2a–m
1
Structures of developed symmetric and asymmetric ureas 3a–j:
Structures of developed N-acylureas 2a–m:
H
H
H
N
H
H
H
N
N
N
N
N
I
O
O
O
O
O
O
O
O
O
O
I
I
I
3a (96%)
N
H
N
3b (91%)
Br
N
N
H
N
H
N
3c (82%)
H
H
H
H
H
H
N
H
N
H
H
N
2c (81%)
2a (93%)
2b (95%)
N
N
Br
N
Cl
O
O
O
O
O
O
O
Br
3e (83%)
Br
O
I
3d (86%)
3f (85%)
F
N
N
N
N
F3C
N
N
H
H
H
H
H
H
H
H
H
N
H
H
N
H
2d (69%)
2e (84%)
2f (62%)
N
N
N
N
O
O
O
O
O
I
O
O
I
O
O
Br
O
Br
3g (81%)
3i (79%)
3h (85%)
N
H
N
N
N
N
N
H
H
H
H
H
I
Cl
H
N
H
N
2g (89%)
2h (87%)
2i (85%)
O
O
O
F
O
O
O
O
3j (76%)
N
N
N
N
H
H
N
N
O
H
H
H
H
Br
Scheme 5 Synthesis of symmetric and asymmetric urea derivatives
3a–j. Reagents and conditions: N-acylbenzotriazole 1 (1.0 equiv.), DPPA
(1.1 equiv.), Et3N (2.0 equiv.), aniline (1.0 equiv.); yields after column
chromatography (silica gel).
2j (76%)
2l (79%)
2k (84%)
O
O
N
N
H
H
F
2m (64%)
O
H
N
DPPA, Et3N, 110 °C
anhyd toluene
S
Scheme 3 Synthesis of N-acylurea derivatives 2a–m from aromatic
R1
R2
Bt
R1
acids. Reagents and conditions: N-acylbenzotriazole 1 (1.0 equiv.), DPPA
(1.1 equiv.), Et3N (2.0 equiv.), benzamide (1.0 equiv.); yields after col-
umn chromatography (silica gel).
O
thiophenols
4a–c
1
Structures of developed thiocarbamates 4a–c:
H
H
N
S
N
S
moderate to excellent yields of compounds 4a–c (Scheme
O
O
6). The structures of the developed compounds were char-
4a (85%)
4b (80%)
1
acterized by H NMR and 13C NMR spectroscopy, and mass
H
N
S
spectrometry.
O
At the end, the established methodology was also inves-
tigated with some weak nucleophiles like phenols in order
to furnish carbamate derivatives via isocyanate intermedi-
ates under Curtius rearrangement. The reaction of (1H-benzo-
[d][1,2,3]triazol-1-yl)(m-tolyl)methanone (1g) was carried
out separately with phenol and p-bromophenol in the pres-
ence of DPPA and Et3N under the optimized conditions, and
as a result the respective carbamate derivatives 5a and 5b
were obtained in moderate yields (Scheme 7).
4c (77%)
Scheme 6 Synthesis of thiocarbamate derivatives 4a–c. Reagents and
conditions: N-acylbenzotriazole 1 (1.0 equiv.), DPPA (1.1 equiv.), Et3N
(2.0 equiv.), thiophenol (1.0 equiv.); yields after column chromatogra-
phy (silica gel).
O
H
N
DPPA, Et3N, 110 °C
anhyd toluene
O
Bt
O
phenols
R
N
5a,b
1g
N
N
DPPA (1.1 equiv.), Et3N (2.0 equiv.)
O
O
benzamide (1.0 equiv.)
Structures of developed carbamates 5a,b:
N
N
H
H
anhyd toluene
O
H
H
2n (80%)
1p (1.0 equiv.)
N
O
N
O
O
O
O
O
Br
5a (45%)
5b (50%)
N
N
H
H
Scheme 7 Synthesis of carbamate derivatives 5a,b. Reagents and
conditions: N-acylbenzotriazole 1g (1.0 equiv.), DPPA (1.1 equiv.), Et3N
(2.0 equiv.), phenol (1.0 equiv.); yields after column chromatography
(silica gel).
2o (obtained in 67% from 1q)
Scheme 4 Synthesis of N-acylurea derivatives 2n,o from aliphatic acids
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

E
M. S. Yadav et al.
Paper
Synthesis
For the quantitative feasibility of this method, the opti-
mized reaction conditions were finally implemented using
1.0 g of (1H-benzo[d][1,2,3]triazol-1-yl)(phenyl)methanone
(1a). The reaction went well and the final product N-acyl-
urea 2a was isolated in 83% yield, which indicates its impor-
tance in scale-up synthesis (Scheme 8).
All chemicals and solvents were of pure analytical category. TLC was
executed on silica gel 60 F254, precoated on aluminum plates, and
seen under a UV lamp (max = 254 nm). Solvents were condensed un-
der low pressure at temperature <55 °C. Column chromatography was
performed on silica gel (230–400 mesh, 100–200 mesh, E. Merck).
EtOAc, n-hexane, and DCM were distilled for the column chromatog-
raphy. Melting points were measured on a digital melting point appa-
ratus (EI 934). 1H and 13C NMR spectra were recorded at 500 and 125
MHz, respectively, on a JEOL DELTA 2 spectrometer. Chemical shifts
are provided in ppm downfield from internal TMS; J values in Hz.
High-resolution mass spectra were taken using a SCIEX X500r Q-TOF
system.
O
H
N
H
N
DPPA (1.1 equiv.)
Et3N (2.0 equiv.)
Bt
benzamide (1.0 equiv.)
anhyd toluene
O
O
1a (1.0 g)
2a (0.893 g)
Scheme 8 Reaction performed on gram scale
Ureas, Acylureas, Carbamates, and Thiocarbamates; General Pro-
cedure
A possible mechanism for the formation of the ureas
and their derivatives like acylureas and thiocarbamates is
depicted in Scheme 9. First of all, reaction of N-acylbenzo-
triazole 1 with the azide donor DPPA furnishes the corre-
sponding acyl azide A via nucleophilic substitution reac-
tion. This acyl azide intermediate undergoes Curtius rear-
rangement to furnish the corresponding isocyanate
intermediate B by the subsequent elimination of molecular
N2. Further, the isocyanate intermediate is trapped by a va-
riety of nucleophiles to give the targeted ureas, carbamates,
and thiocarbamates.
N-Acylbenzotriazole 1 (1.0 equiv.) and diphenylphosphoryl azide
(DPPA, 1.1 equiv.) in anhydrous toluene (3 mL) was taken into a sealed
tube, and shaken for 5 min. Then, the required nucleophile (e.g.,
amine, benzamide, phenol, or thiol; 1.0 equiv.) was added, followed
by addition of Et3N (2.0 equiv.) as base. Further, the resulting reaction
mixture was stirred for 3–4 h at 110 °C in a sealed tube. After comple-
tion of the reaction (monitored by TLC), the reaction mixture was
concentrated under reduced pressure and subjected to column chro-
matography (n-hexane/EtOAc) to afford the corresponding urea, N-
acylurea, carbamate, or thiocarbamate as the desired product.
N-(Phenylcarbamoyl)benzamide (2a)16b,28
White crystals; yield: 0.200 g (93%); Rf = 0.5 (20% EtOAc/n-hexane);
mp 210–212 °C.
1H NMR (500 MHz, DMSO-d6):  = 11.02 (s, 1 H), 10.82 (s, 1 H), 8.01
(d, J = 7.5 Hz, 2 H), 7.64 (d, J = 7.0 Hz, 1 H), 7.58–7.51 (m, 4 H), 7.36–
7.33 (m, 2 H), 7.11–7.08 (m, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 168.7, 151.0, 137.6, 133.0, 132.2,
128.9, 128.5, 128.2, 123.7, 119.8.
DPPA
O
O
N
R1
N C O
R1
N
R1
Bt
N
B
1
A
N2
Bt
R2NH2
NEt3
H
O
O
H
H
N
N
X
R1
R1
R
N
RXH
R2
R1
N
C
O
R1
N
N
R2
O
H
H
(X = S, O)
O
thiocarbamates
and carbamates
N-((2-Iodophenyl)carbamoyl)benzamide (2b)
isocyanate (B)
acylurea
urea
White solid; yield: 0.199 g (95%); Rf = 0.4 (20% EtOAc/n-hexane); mp
224–225 °C.
Scheme 9 Plausible mechanism involving the Curtius rearrangement
1H NMR (500 MHz, DMSO-d6):  = 11.19 (s, 1 H), 11.03 (s, 1 H), 8.08–
8.03 (m, 3 H), 7.90 (d, J = 7.5 Hz, 1 H), 7.67–7.64 (m, 1 H), 7.55–7.52
(m, 2 H), 7.42–7.39 (m, 1 H), 6.93–6.90 (m, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 168.7, 151.3, 139.1, 138.9, 133.1,
132.0, 128.7, 128.5, 128.4, 126.0, 122.7, 90.9.
In conclusion, a practical and straightforward tool has
been developed for the high-yielding synthesis of a diverse
range of ureas, acylureas, carbamates, and thiocarbamates
by utilizing N-acylbenzotriazoles as suitable precursors and
readily available DPPA as azide source under one-pot condi-
tions. 1H-Benzotriazole is the byproduct which is nontoxic
and water soluble, and moreover can be easily removed
from the reaction mixture.27 Most of the developed ureas
and N-acylureas were purified by simple filtration followed
by washing with appropriate solvents and thus a column
chromatography step was avoided. Therefore, the devised
methodology demonstrates a practical applicability in aca-
demia and industry.
HRMS (ESI+): m/z [M + H] calcd for C14H12IN2O2: 366.9943; found:
366.9942.
N-((3-Bromophenyl)carbamoyl)benzamide (2c)
White crystals; yield: 0.171 g (81%); Rf = 0.5 (20% EtOAc/n-hexane);
mp 203–204 °C.
1H NMR (500 MHz, DMSO-d6):  = 11.08 (s, 1 H), 10.87 (s, 1 H), 8.01
(d, J = 8.0 Hz, 2 H), 7.96 (s, 1 H), 7.66–7.63 (m, 1 H), 7.55–7.48 (m, 3
H), 7.30 (d, J = 6.5 Hz, 2 H).
13C NMR (125 MHz, DMSO-d6):  = 168.6, 151.1, 139.2, 133.0, 132.1,
130.8, 128.5, 128.2, 126.3, 122.1, 121.6, 118.8.
HRMS (ESI+): m/z [M + H] calcd for C14H12BrN2O2: 319.0082; found:
319.0073.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

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M. S. Yadav et al.
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Synthesis
N-((3-Fluorophenyl)carbamoyl)benzamide (2d)
N-((2-Chlorophenyl)carbamoyl)benzamide (2i)14b
White solid; yield: 0.147 g (69%); Rf = 0.5 (20% EtOAc/n-hexane); mp
White solid; yield: 0.181 g (85%); Rf = 0.6 (20% EtOAc/n-hexane); mp
178–180 °C.
220–221 °C.
1H NMR (500 MHz, DMSO-d6):  = 11.09 (s, 1 H), 10.92 (s, 1 H), 8.01
(d, J = 8.0 Hz, 2 H), 7.66–7.52 (m, 4 H), 7.38–7.31 (m, 2 H), 6.93 (t, J =
7.5 Hz, 1 H).
1H NMR (500 MHz, DMSO-d6):  = 11.42 (s, 1 H), 11.25 (s, 1 H), 8.31
(d, J = 8.5 Hz, 1 H), 8.03 (d, J = 7.5 Hz, 2 H), 7.67–7.64 (m, 1 H), 7.55–
7.52 (m, 3 H), 7.38–7.36 (m, 1 H), 7.15–7.12 (m, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 168.6, 163.2, 161.2, 151.1, 139.4,
139.3, 133.1, 132.1, 130.6, 130.5, 129.0, 128.6, 128.3, 123.9, 119.8,
115.6, 110.3, 110.1, 106.8, 106.6.
13C NMR (125 MHz, DMSO-d6):  = 169.1, 151.1, 134.7, 133.2, 132.0,
129.3, 128.6, 128.4, 127.9, 124.7, 122.4, 121.5.
N-((2-Methoxyphenyl)carbamoyl)benzamide (2j)29
HRMS (ESI+): m/z [M + H] calcd for C14H12FN2O2: 259.0883; found:
259.0867.
White solid; yield: 0.162 g (76%); Rf = 0.4 (20% EtOAc/n-hexane); mp
222–223 °C.
N-((4-Chlorophenyl)carbamoyl)benzamide (2e)14b
1H NMR (500 MHz, DMSO-d6):  = 11.20 (s, 1 H), 11.02 (s, 1 H), 8.20
(d, J = 7.5 Hz, 1 H), 8.01 (d, J = 8.0 Hz, 2 H), 7.65–7.62 (m, 1 H), 7.54–
7.51 (m, 2 H), 7.07–7.06 (m, 2 H), 6.96–6.93 (m, 1 H), 3.88 (s, 3 H).
White solid; yield: 0.179 g (84%); Rf = 0.5 (20% EtOAc/n-hexane); mp
194–196 °C.
1H NMR (500 MHz, DMSO-d6):  = 11.08 (s, 1 H), 10.85 (s, 1 H), 8.01
(d, J = 8.0 Hz, 2 H), 7.66–7.61 (m, 3 H), 7.54–7.51 (m, 2 H), 7.41–7.38
(m, 2 H).
13C NMR (125 MHz, DMSO-d6):  = 168.7, 151.0, 148.2, 133.1, 132.3,
128.6, 128.3, 127.1, 123.7, 120.7, 119.3, 110.9, 56.0.
N-((2-Bromophenyl)carbamoyl)benzamide (2k)30
13C NMR (125 MHz, DMSO-d6):  = 168.6, 151.1, 136.6, 133.0, 132.2,
128.8, 128.5, 128.2, 127.4, 121.4.
White solid; yield: 0.177 g (84%); Rf = 0.5 (20% EtOAc/n-hexane); mp
216–218 °C.
1H NMR (500 MHz, DMSO-d6):  = 11.31 (s, 1 H), 11.22 (s, 1 H), 8.26
(d, J = 8.0 Hz, 1 H), 8.03 (d, J = 8.0 Hz, 2 H), 7.69–7.64 (m, 2 H), 7.53 (t,
J = 7.5 Hz, 2 H), 7.42–7.39 (m, 1 H), 7.09–7.06 (m, 1 H).
N-((3-(Trifluoromethyl)phenyl)carbamoyl)benzamide (2f)
White solid; yield: 0.131 g (62%); Rf = 0.5 (20% EtOAc/n-hexane); mp
162–164 °C.
1H NMR (500 MHz, DMSO-d6):  = 11.13 (s, 1 H), 11.00 (s, 1 H), 8.10 (s,
1 H), 8.02 (d, J = 7.5 Hz, 2 H), 7.80 (d, J = 7.5 Hz, 1 H), 7.67–7.64 (m, 1
H), 7.59–7.52 (m, 3 H), 7.45 (d, J = 7.5 Hz, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 169.0, 151.2, 136.0, 133.2, 132.6,
132.0, 128.6, 128.46, 128.42, 125.4, 122.1, 113.2.
N-(m-Tolylcarbamoyl)benzamide (2l)14b
13C NMR (125 MHz, DMSO-d6):  = 168.6, 151.3, 138.5, 133.1, 132.1,
130.1, 129.7, 128.5, 128.3, 123.7, 120.1, 119.8, 116.0.
White solid; yield: 0.169 g (79%); Rf = 0.45 (20% EtOAc/n-hexane); mp
19F NMR (471 MHz, DMSO-d6):  = –61.15.
167–168 °C.
1H NMR (500 MHz, DMSO-d6):  = 11.01 (s, 1 H), 10.79 (s, 1 H), 8.01
(d, J = 8.0 Hz, 2 H), 7.66–7.63 (m, 1 H), 7.53 (t, J = 8.0 Hz, 2 H), 7.39–
7.37 (m, 2 H), 7.24–7.21 (m, 1 H), 6.92 (d, J = 8.0 Hz, 1 H), 2.30 (s, 3 H).
HRMS (ESI+): m/z [M + H] calcd for C15H12F3N2O2: 309.0851; found:
309.0847.
13C NMR (125 MHz, DMSO-d6):  = 168.7, 151.0, 138.3, 137.5, 133.0,
2-Iodo-N-((2-iodophenyl)carbamoyl)benzamide (2g)
132.2, 128.8, 128.5, 128.2, 124.4, 120.2, 116.9, 21.0.
White solid; yield: 0.250 g (89%); Rf = 0.4 (20% EtOAc/n-hexane); mp
198–199 °C.
N-((2-Fluorophenyl)carbamoyl)benzamide (2m)
1H NMR (500 MHz, DMSO-d6):  = 11.34 (s, 1 H), 10.65 (s, 1 H), 8.06
(d, J = 8.5 Hz, 1 H), 7.93–7.89 (m, 2 H), 7.53–7.47 (m, 2 H), 7.42–7.39
(m, 1 H), 7.26–7.23 (m, 1 H), 6.94–6.91 (m, 1 H).
White solid; yield: 0.137 g (64%); Rf = 0.55 (20% EtOAc/n-hexane); mp
220–221 °C.
1H NMR (500 MHz, DMSO-d6):  = 11.23 (s, 1 H), 11.16 (s, 1 H), 8.20 (t,
J = 8.0 Hz, 1 H), 8.03 (d, J = 8.0 Hz, 2 H), 7.66–7.64 (m, 1 H), 7.55–7.52
(m, 2 H), 7.33–7.30 (m, 1 H), 7.22–7.20 (m, 1 H), 7.15–7.13 (m, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 169.0, 151.3, 151.0, 137.4, 133.1,
132.0, 128.5, 128.3, 125.8, 124.7, 124.37, 124.32, 121.4, 115.2, 115.1.
13C NMR (125 MHz, DMSO-d6):  = 171.1, 150.7, 140.6, 139.2, 139.1,
138.8, 131.8, 128.8, 128.3, 128.0, 126.1, 122.5, 93.1, 90.8.
HRMS (ESI+): m/z [M + H] calcd for C14H11I2N2O2: 492.8910; found:
492.8897.
19F NMR (471 MHz, DMSO-d6):  = –124.87.
2-Iodo-N-(phenylcarbamoyl)benzamide (2h)
White solid; yield: 0.285 g (87%); Rf = 0.4 (20% EtOAc/n-hexane); mp
HRMS (ESI+): m/z [M + H] calcd for C14H12FN2O2: 259.0883; found:
224–225 °C.
259.0880.
1H NMR (500 MHz, DMSO-d6):  = 11.14 (s, 1 H), 10.44 (s, 1 H), 7.92
(d, J = 7.5 Hz, 1 H), 7.57 (d, J = 8.0 Hz, 2 H), 7.50–7.47 (m, 2 H), 7.36–
7.33 (m, 2 H), 7.26–7.18 (m, 1 H), 7.12–7.09 (m, 1 H).
N-((3S,5S,7S)-Adamantan-1-ylcarbamoyl)benzamide (2n)
White crystals; yield: 0.169 g (80%); Rf = 0.55 (20% EtOAc/n-hexane);
13C NMR (125 MHz, DMSO-d6):  = 171.9, 151.3, 139.8, 137.6, 132.7,
mp 203–204 °C.
1H NMR (500 MHz, DMSO-d6):  = 10.46 (s, 1 H), 8.64 (s, 1 H), 7.92 (d,
J = 8.0 Hz, 2 H), 7.60–7.58 (m, 1 H), 7.49–7.46 (m, 2 H), 2.04 (s, 3 H),
1.98 (s, 6 H), 1.64 (s, 6 H).
129.89, 129.85, 128.9, 128.7, 125.0, 120.6, 93.0.
HRMS (ESI+): m/z [M + H] calcd for C14H12IN2O2: 366.9943; found:
366.9934.
13C NMR (125 MHz, DMSO-d6):  = 168.6, 151.6, 132.6, 128.4, 128.0,
50.4, 41.2, 35.8, 28.8.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

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Synthesis
HRMS (ESI+): m/z [M + H] calcd for C18H23N2O2: 299.1760; found:
13C NMR (125 MHz, DMSO-d6):  = 152.1, 139.4, 137.0, 132.4, 128.8,
299.1732.
128.0, 124.0, 122.2, 122.1, 118.2, 113.0.
N-(Undecylcarbamoyl)benzamide (2o)
1-(2,5-Dibromophenyl)-3-phenylurea (3f)
Off-white solid; yield: 0.141 g (67%); Rf = 0.45 (20% EtOAc/n-hexane);
White solid; yield: 0.166 g (85%); Rf = 0.45 (20% EtOAc/n-hexane); mp
mp 85–87 °C.
205–206 °C.
1H NMR (500 MHz, DMSO-d6):  = 10.62 (s, 1 H), 8.65 (s, 1 H), 7.94 (d,
J = 7.5 Hz, 2 H), 7.59 (d, J = 7.0 Hz, 1 H), 7.49–7.46 (m, 2 H), 3.22–3.15
(m, 2 H), 1.26–1.21 (m, 18 H), 0.83–0.81 (m, 3 H).
1H NMR (500 MHz, DMSO-d6):  = 9.59 (s, 1 H), 8.35 (d, J = 1.5 Hz, 1
H), 8.25 (s, 1 H), 7.56 (d, J = 9.0 Hz, 1 H), 7.46 (d, J = 8.5 Hz, 2 H), 7.29
(t, J = 7.5 Hz, 2 H), 7.15–7.12 (m, 1 H), 7.01 (s, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 168.2, 153.5, 132.7, 132.6, 128.4,
13C NMR (125 MHz, DMSO-d6):  = 151.9, 139.1, 138.6, 134.0, 128.9,
128.1, 67.0, 54.8, 31.3, 29.1, 29.0, 28.74, 28.72, 26.3, 25.1, 22.1, 13.9.
126.2, 123.5, 122.3, 120.7, 118.3, 111.2.
HRMS (ESI+): m/z [M + H] calcd for C19H31N2O2: 319.2386; found:
HRMS (ESI+): m/z [M + H] calcd for C13H11Br2N2O: 370.9218; found:
319.2362.
370.9190.
1,3-Diphenylurea (3a)16b
1-(3-Bromophenyl)-3-phenylurea (3g)34
White crystals; yield: 0.182 g (96%); Rf = 0.35 (20% EtOAc/n-hexane);
White crystals; yield: 0.156 g (81%); Rf = 0.3 (20% EtOAc/n-hexane);
mp 192–193 °C.
mp 172–173 °C.
1H NMR (500 MHz, DMSO-d6):  = 8.61 (s, 2 H), 7.45 (d, J = 8.5 Hz, 4
H), 7.28–7.25 (m, 4 H), 6.97–6.94 (m, 2 H).
13C NMR (125 MHz, DMSO-d6):  = 152.4, 139.6, 128.7, 121.7, 118.1.
1H NMR (500 MHz, DMSO-d6):  = 8.84 (s, 1 H), 8.71 (s, 1 H), 7.86 (s, 1
H), 7.45 (d, J = 7.5 Hz, 2 H), 7.30–7.25 (m, 3 H), 7.23–7.20 (m, 1 H),
7.13 (d, J = 8.0 Hz, 1 H), 6.98–6.95 (m, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 152.3, 141.3, 139.3, 130.6, 128.7,
1-(2-Iodophenyl)-3-phenylurea (3b)31
124.2, 122.0, 121.6, 120.3, 118.3, 116.9.
White solid; yield: 0.176 g (91%); Rf = 0.5 (20% EtOAc/n-hexane); mp
182–183 °C.
1-(2-Methoxyphenyl)-3-phenylurea (3h)16b
White crystals; yield: 0.162 g (85%); Rf = 0.35 (20% EtOAc/n-hexane);
mp 144–148 °C.
1H NMR (500 MHz, DMSO-d6):  = 9.30 (s, 1 H), 8.22 (s, 1 H), 8.14 (d,
J = 7.5 Hz, 1 H), 7.46 (d, J = 8.0 Hz, 2 H), 7.27 (t, J = 7.5 Hz, 2 H), 6.99–
6.87 (m, 4 H), 3.85 (s, 3 H).
1H NMR (500 MHz, DMSO-d6):  = 9.39 (s, 1 H), 7.86 (s, 1 H), 7.83–
7.80 (m, 2 H), 7.45 (d, J = 7.5 Hz, 2 H), 7.34–7.26 (m, 3 H), 6.98–6.95
(m, 1 H), 6.84–6.81 (m, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 152.3, 139.8, 139.5, 138.9, 128.8,
128.5, 125.0, 123.0, 122.0, 118.1, 91.3.
13C NMR (125 MHz, DMSO-d6):  = 152.4, 147.6, 139.8, 128.8, 128.7,
1,3-Bis(2-iodophenyl)urea (3c)32
121.8, 121.7, 120.5, 118.3, 117.9, 110.7, 55.7.
White solid; yield: 0.217 g (82%); Rf = 0.5 (20% EtOAc/n-hexane); mp
>220 °C.
1-(2-Bromophenyl)-3-phenylurea (3i)33
White crystals; yield: 0.152 g (79%); Rf = 0.5 (20% EtOAc/n-hexane);
mp 171–173 °C.
1H NMR (500 MHz, DMSO-d6):  = 9.44 (s, 1 H), 8.12 (s, 1 H), 8.06–
8.05 (m, 1 H), 7.61–7.59 (m, 1 H), 7.46–7.44 (m, 2 H), 7.34–7.27 (m, 3
H), 6.99–6.94 (m, 2 H).
13C NMR (125 MHz, DMSO-d6):  = 152.1, 139.4, 137.0, 132.4, 128.8,
128.0, 124.0, 122.1, 122.0, 118.1, 112.9.
1H NMR (500 MHz, DMSO-d6):  = 8.54 (s, 2 H), 7.84 (d, J = 7.5 Hz, 2
H), 7.70 (d, J = 7.5 Hz, 2 H), 7.33 (t, J = 7.5 Hz, 2 H), 6.87–6.84 (m, 2 H).
13C NMR (125 MHz, DMSO-d6):  = 152.8, 139.8, 138.9, 128.5, 125.6,
124.4, 92.5.
HRMS (ESI+): m/z [M + H] calcd for C13H11I2N2O: 464.8961; found:
464.8936.
1-(2-Iodophenyl)-3-phenylurea (3d)31
1-(2-Fluorophenyl)-3-phenylurea (3j)35
White solid; yield: 0.260 g (86%); Rf = 0.5 (20% EtOAc/n-hexane); mp
182–183 °C.
1H NMR (500 MHz, DMSO-d6):  = 9.40 (s, 1 H), 7.86 (s, 1 H), 7.82 (d,
J = 8.0 Hz, 2 H), 7.45 (d, J = 8.0 Hz, 2 H), 7.35–7.26 (m, 3 H), 6.98–6.95
(m, 1 H), 6.82 (t, J = 7.5 Hz, 1 H).
13C NMR (125 MHz, DMSO-d6):  = 152.3, 139.8, 139.5, 138.9, 128.8,
128.5, 125.0, 123.0, 121.9, 118.1, 91.3.
White crystals; yield: 0.145 g (76%); Rf = 0.5 (20% EtOAc/n-hexane);
mp 176–177 °C.
1H NMR (500 MHz, DMSO-d6):  = 9.06 (s, 1 H), 8.53 (s, 1 H), 8.15–
8.12 (m, 1 H), 7.44 (d, J = 7.5 Hz, 2 H), 7.29–7.20 (m, 3 H), 7.14–7.11
(m, 1 H), 6.99–6.97 (m, 2 H).
13C NMR (125 MHz, DMSO-d6):  = 152.9, 152.1, 150.9, 139.4, 128.8,
127.59, 127.51, 124.4, 122.3, 122.0, 120.4, 118.0, 115.0, 114.8.
19F NMR (471 MHz, DMSO-d6):  = –125.22.
1-(2-Bromophenyl)-3-phenylurea (3e)33
White solid; yield: 0.216 g (83%); Rf = 0.5 (20% EtOAc/n-hexane); mp
171–173 °C.
S-Phenyl Phenylcarbamothioate (4a)36
Off-white solid; yield: 0.174 g (85%); Rf = 0.8 (20% EtOAc/n-hexane);
mp 105–106 °C.
1H NMR (500 MHz, CDCl3):  = 7.62–7.60 (m, 2 H), 7.46–7.45 (m, 3 H),
1H NMR (500 MHz, DMSO-d6):  = 9.44 (s, 1 H), 8.11 (s, 1 H), 8.06–
8.04 (m, 1 H), 7.61–7.59 (m, 1 H), 7.45 (d, J = 7.5 Hz, 2 H), 7.34–7.27
(m, 3 H), 6.99–6.94 (m, 2 H).
7.37–7.36 (m, 2 H), 7.31–7.28 (m, 2 H), 7.12–7.09 (m, 2 H).
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

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M. S. Yadav et al.
Paper
Synthesis
13C NMR (125 MHz, CDCl3):  = 164.3, 137.4, 135.5, 129.9, 129.5,
129.1, 127.9, 124.6, 119.5.
Acknowledgment
The authors sincerely thank CISC-Banaras Hindu University, Varanasi
for all the infrastructural facility.
S-o-Tolyl Phenylcarbamothioate (4b)37
White solid; yield: 0.174 g (80%); Rf = 0.8 (20% EtOAc/n-hexane); mp
137–138 °C.
Supporting Information
1H NMR (500 MHz, CDCl3):  = 7.53 (d, J = 7.5 Hz, 1 H), 7.31–7.27 (m, 3
Supporting information for this article is available online at
https://doi.org/10.1055/a-1399-3823. Included are copies of 1H and
13C NMR spectra for all developed ureas and their derivatives, carba-
H), 7.22–7.17 (m, 4 H), 7.03–6.98 (m, 2 H), 2.42 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 164.0, 143.0, 137.5, 137.0, 131.1,
130.7, 129.1, 127.5, 127.0, 124.5, 119.4, 20.8.
mates, and thiocarbamates.
S
u
p
p
ortingInformationS
u
p
p
ortingInformatio
n
S-p-Tolyl 3,5-Dimethylphenylcarbamothioate (4c)
White solid; yield: 0.166 g (77%); Rf = 0.85 (20% EtOAc/n-hexane); mp
112–114 °C.
References
(1) (a) Katritzky, A. R.; Kirichenko, N.; Rogovoy, B. V. ARKIVOC 2003,
(viii), 8. (b) Ghosh, A. K.; Brindisi, M. J. Med. Chem. 2020, 63,
2751. (c) Barker, T. J.; Duncan, K. K.; Otrubova, K.; Boger, D. L.
ACS Med. Chem. Lett. 2013, 4, 985. (d) Sidda, J. D.; Song, L.; Poon,
V.; Al-Bassam, M.; Lazos, O.; Buttner, M. J.; Challis, G. L.; Corre,
C. Chem. Sci. 2014, 5, 86. (e) Schwartz, B. D.; Skinner-Adams, T.
S.; Andrews, K. T.; Coster, M. J.; Edstein, M. D.; MacKenzie, D.;
Charman, S. A.; Koltun, M.; Blundell, S.; Campbell, A.; Pouwer, R.
H.; Quinn, R. J.; Beattie, K. D.; Healy, P. C.; Davis, R. A. Org.
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1H NMR (500 MHz, CDCl3):  = 7.48–7.46 (m, 2 H), 7.25–7.24 (m, 2 H),
6.98 (s, 3 H), 6.72 (s, 1 H), 2.39 (s, 3 H), 2.24 (s, 6 H).
13C NMR (125 MHz, CDCl3):  = 164.6, 140.3, 138.8, 137.3, 135.5,
130.3, 126.2, 124.6, 117.1, 21.3, 21.2.
HRMS (ESI+): m/z [M + H] calcd for C16H18NOS: 272.1109; found:
272.1066.
Phenyl m-Tolylcarbamate (5a)
White solid; yield: 0.086 g (45%); Rf = 0.7 (20% EtOAc/n-hexane); mp
103–106 °C.
1H NMR (500 MHz, CDCl3):  = 7.32 (t, J = 8.0 Hz, 2 H), 7.24–7.11 (m, 6
H), 6.85 (s, 2 H), 2.27 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 151.4, 150.5, 139.1, 137.2, 129.3,
128.9, 125.6, 124.7, 121.6, 119.3, 115.8, 21.4.
HRMS (ESI+): m/z [M + H] calcd for C14H14NO2: 228.1020; found:
228.1024.
(2) (a) Bogolubsky, A. V.; Moroz, Y. S.; Mykhailiuk, P. K.; Granat, D.
S.; Pipko, S. E.; Konovets, A. I.; Doroschuk, R.; Tolmachev, A. ACS
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4-Bromophenyl m-Tolylcarbamate (5b)
White solid; yield: 0.129 g (50%); Rf = 0.7 (20% EtOAc/n-hexane); mp
110–112 °C.
1H NMR (500 MHz, CDCl3):  = 7.51–7.49 (m, 2 H), 7.28 (s, 1 H), 7.24–
7.21 (m, 2 H), 7.09–7.07 (m, 2 H), 6.94–6.89 (m, 2 H), 2.35 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 151.0, 149.6, 139.1, 136.9, 132.3,
129.0, 124.9, 123.4, 119.4, 118.6, 115.8, 21.4.
HRMS (ESI+): m/z [M + H] calcd for C14H13BrNO2: 306.0125; found:
306.0118.
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Conflict of Interest
The authors declare no conflict of interest.
Funding Information
The authors sincerely thank the Science and Engineering Research
Board (SERB), New Delhi (Grant No. EMR/2016/001123) and the
Council of Scientific and Industrial Research (CSIR), New Delhi
[Scheme No. 02(0345)/19/EMR-II] for funding. M.S.Y. and A.K.A. ac-
knowledge CSIR for fellowships (SRF), while S.K.S. thanks the Univer-
sity Grants Commission (UGC) for a JRF.Science
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© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I