Aryliminophosphoranes as Key Intermediates in the One-Pot Synthesis of 1-Aryl-1,3-dihydro-2H-benzimidazol-2-ones from N-Aryl-2-nitrosoanilines and Carbon Dioxide under Mild Metal-Free Conditions

Article abstract of DOI:10.1055/s-0035-1561301

A new and convenient protocol is presented for the synthesis of 1-arylbenzimidazol-2-ones by a one-pot reaction of N-aryl-2-nitrosoanilines using solid carbon dioxide as a source of the key carbonyl moiety. The metal-free process is carried out under mild conditions and is compatible with a variety of substituents. The atom economy of the synthesis of the starting nitrosoanilines, accomplished by substitution of hydrogen, makes the entire synthesis of the target compounds environmentally friendly.

Full text of DOI:10.1055/s-0035-1561301

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–H
paper
A
E. Łukasik, Z. Wróbel
Paper
Synthesis
Aryliminophosphoranes as Key Intermediates in the One-Pot
Synthesis of 1-Aryl-1,3-dihydro-2H-benzimidazol-2-ones from
N-Aryl-2-nitrosoanilines and Carbon Dioxide under Mild Metal-
Free Conditions
Emilia Łukasik
Zbigniew Wróbel*
Institute of Organic Chemistry, Polish Academy of
Sciences, Kasprzaka 44, 01-224 Warsaw, Poland
zbigniew.wrobel@icho.edu.pl
Received: 23.10.2015
Accepted after revision: 27.11.2015
Published online: 07.01.2016
The above uses of aryliminophosphoranes do not ex-
haust their synthetic potential. The compounds appear to
be perfect reagents for the upgrading of carbon dioxide by
incorporation into heterocyclic systems. Because of the low
cost and lack of toxicity of the compound, the conversion of
carbon dioxide into important chemicals has recently re-
ceived increasing attention.4 Incorporation of carbon diox-
ide into heteronucleophiles opens a door to the synthesis of
five- or six-membered heterocyclic compounds, which is of
vital importance from the viewpoint of the production of
biologically and pharmacologically significant structures.
The so-called chemical fixation of carbon dioxide has been
successfully applied in the synthesis of cyclic carbonates,5
ureas,6 quinazoline-2,4(1H,3H)-diones,7 2-benzothiazol-
ones, benzimidazoles,8 and 2-benzimidazolones.9,10 The last
compounds were obtained from suitable o-arylenedi-
amines by reaction with carbon dioxide in a 1,8-diazabicyc-
lo[5.4.0]undec-7-ene-based ionic liquid10 or in N-meth-
ylpyrrolidin-2-one promoted by a tungstate catalyst.9 Al-
though both processes were performed at high
temperatures (120 and 140 °C, respectively), the former
needed 9 MPa of carbon dioxide to be effective. Although
these two methods represent a promising synthetic ap-
proach, superior to earlier procedures,11 they have some
obvious inconveniences related to the rather harsh reaction
conditions and the availability of the starting materials.
Among the general methods available for the synthesis
of 2-benzimidazolones, only a few have been used for the
preparation of 1-aryl derivatives (Scheme 1). Intramolecu-
lar copper(I)-mediated arylation of the appropriate 1,3-di-
arylureas12 or cyclization of o-arylenediamines with phos-
DOI: 10.1055/s-0035-1561301; Art ID: ss-2015-t0619-op
Abstract A new and convenient protocol is presented for the synthesis
of 1-arylbenzimidazol-2-ones by a one-pot reaction of N-aryl-2-nitro-
soanilines using solid carbon dioxide as a source of the key carbonyl
moiety. The metal-free process is carried out under mild conditions and
is compatible with a variety of substituents. The atom economy of the
synthesis of the starting nitrosoanilines, accomplished by substitution
of hydrogen, makes the entire synthesis of the target compounds envi-
ronmentally friendly.
Key words annulations, heterocycles, cyclizations, nitroso com-
pounds, fused-ring systems
In 2014, we described a simple synthesis of 2-(arylami-
no)aryliminophosphoranes from N-aryl-2-nitrosoanilines
by a Cadogan-type reaction with triphenylphosphine,1a and
we subsequently demonstrated the versatility of the prod-
ucts as 1,2-arylenediamine equivalents in reactions with
isocyanates, nitrous acid, or carbon disulfide, leading effi-
ciently to 2-aminobenzimidazoles,1a benzotriazoles1b and
2-thiobenzimidazoles,2 respectively. Because N-aryl-2-ni-
trosoanilines can be obtained through substitution of hy-
drogen in nitroarenes by arylamines,3 the synthesis of 2-
(arylamino)aryliminophosphoranes does not require SNAr
substitution of halogens (mainly fluorine) in o-haloni-
troarenes. When not commercially available, the latter sub-
strates can be difficult to synthesize. Therefore, an ap-
proach that omits the introduction and subsequent wastage
of halogen substituents can be considered as environmen-
tally friendly chemistry.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

B
E. Łukasik, Z. Wróbel
Paper
Synthesis
gene,13 triphosgene (bistrichloromethyl carbonate),14
urea,15a,b carbonyldiimide,15c–e or carbon monoxide15f are
frequently adopted approaches.
ple, the simple structures shown in Figure 1, such as 1-phe-
nyl-1,3-dihydro-2H-benzimidazol-2-one (A) and 6-chloro-
1-phenyl-1,3-dihydro-2H-benzimidazol-2-one (B) exhibit
antisecretory and antiulcer activities.18 The trifluoromethyl
derivatives C and D have well-documented BK channel-
opening activity.19 Compound E has not been prepared, but
its bioactivity has been predicted on the basis of molecular
modelling.20 Compound F demonstrates evidence of ATPase
inhibition.13b
Here, we present a reaction of 2-(arylamino)arylimino-
phosphoranes with carbon dioxide to give 1-aryl-1,3-dihy-
dro-2H-benzimidazol-2-ones. The process involves conden-
sation of carbon dioxide with the iminophosphorane func-
tion,21 followed by cyclization of the nonisolable
intermediate by reaction of the isocyanate group with the
arylamino group.
H2N
phosgene, urea, CO,
or carbonyldiimides
H
N
NH2
O
CO2, ionic liquids
CO2, tungstate cat.
N
H
R
R
SNAr or Cu(I) cat.
arylation
H2N
R
phosgene, urea,
or carbonyldiimides
H
N
H
N
Ar
O
CO2, ionic liquids
CO2, tungstate cat.
N
Ar
R
O
NO2
NH2
N
Cu(I) or
[Pd]
X
H
N
H
N
NHAr
PZ3
t-BuOK
+
X = I, Br
O
Y
Y
X
R
X
3
4
5
Scheme 1 Common synthetic routes to 1-arylbenzimidazol-2-ones
O
PZ3
C
Reported occasionally are nonregioselective arylation of
1,3-dihydro-2-benzimidazolones through aromatic nucleo-
philic substitution with activated arenes16 and copper(I)-
mediated arylation with bromo- or iodoarenes17a or with
boronic acids.17b,c All these methods suffer from various in-
conveniences. Some require elevated temperatures and/or
high pressures, whereas others use expensive or toxic and
dangerous reagents.
N
N
H
H
H
N
N
N
CO2
O
N
X
Y
Y
X
X
1
Y
2
Scheme 2 Three-step synthetic route from nitroarenes to 1-arylbenz-
imidazol-2-ones through iminophosphorane intermediates
The target 1-arylbenzimidazol-2-ones are important
compounds because of their biological activity. For exam-
The transformation of the iminophosphoranes 1 into 1-
aryl-1,3-dihydro-2H-benzimidazol-2-ones 2 concludes a
reaction sequence (Scheme 2) in which nucleophilic substi-
tution of hydrogen in a nitroarene 3 with arylamine 4 pro-
vides a 2-nitrosoaniline 5 that is transformed into the ap-
propriate iminophosphorane 1. The idea was to provide a
safe and environmentally friendly protocol for the synthe-
sis of the title compounds from simple reagents, such as ni-
troarenes, without wastage of halogen atoms in substitu-
tion processes, and which eliminates the need for any re-
duction step and avoids the use of metallic, toxic, or
dangerous reagents.
To determine the optimal conditions for the reaction,
we examined the reactions of iminophosphoranes 1 (Z =
Ph) obtained according to the reported procedures from the
corresponding 2-nitrosoanilines and triphenylphosphine.
In the initial experiments, the iminophosphoranes were
stirred under a balloon filled with gaseous carbon dioxide
at near-atmospheric pressure. The reaction was slow and
H
N
H
N
H
N
F3C
O
O
O
N
N
N
Cl
OH
F3C
A
B
C
H
N
H
H
F3C
F3C
N
N
O
O
O
N
N
N
OH
OH
Cl
Cl
OH
D
F
E
Figure 1 Biologically active 1,3-dihydro-2H-benzimidazol-2-ones
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

C
E. Łukasik, Z. Wróbel
Paper
Synthesis
needed several weeks to achieve completion. However,
when a solution of iminophosphorane 1 was treated with
solid carbon dioxide at low temperature in a sealed glass
ampoule and then stirred at ambient temperature, the reac-
tion time was significantly reduced to a few days. The pres-
sure in the vessel, measured on one occasion during the re-
action, did not exceed 2 bar (~0.2 MPa). We examined the
reaction of iminophosphorane 1a under these conditions in
various solvents (Table 1).
substituents, giving high yields even when bulky ortho
groups were present in the N-aryl ring (e.g., 2a or 2p).
Therefore, the reaction has general character. The results
collected in Figure 2 show that it can be successfully ap-
plied in syntheses of compounds with known biological ac-
tivities, as mentioned above and shown in Figure 1 (2e = A,
2b = B, and 2m = E). The methoxy-substituted benzimidaz-
olones 2k, 2l, and 2n are convenient direct intermediates
for the synthesis of the corresponding hydroxybenzimidaz-
olones C, D, and F, respectively.14a,19
Triphenylphosphine, used as the phosphorus(III) re-
agent PZ3 in the reaction, is convenient on a small laborato-
ry scale and permits the production of crystalline interme-
diate triphenyliminophosphoranes 1; however, it suffers
from several serious drawbacks. The high molecular mass
of the triphenylphosphoranylidene moiety in 1, which is
lost in the subsequent reaction step, markedly reduces the
atom economy of the transformation. Furthermore, the for-
mation of large amounts of triphenylphosphine oxide by-
product, which is sparingly soluble in most solvents and
difficult to remove, is not easily acceptable on a larger scale
and is not environmentally friendly. To overcome these
problems, we examined some other trivalent phosphorus
compounds as alternatives to triphenylphosphine (Table 2).
Table 1 Solvent Effect on the Synthesis of Benzimidazolone 2a by
the Reaction of Carbon Dioxide with Iminophosphorane 1a (X = Cl;
Y = 2-I-4-Cl; Z = Ph)
Entry
Solvent
Time (d)
Yielda (%) of 2a
1
2
3
4
5
6
7
8
9
THF
7
2
85
CH2Cl2
acetone
EtOAc
DMF
83
7
91
16
5
95
91
MeCN
MeOH
toluene
THF–H2Oc
12
3
63b
traces
87
2
15
34d
Table 2 Formation of Iminophosphoranes 1h–w by Using Selected
Phosphorus(III) Reagents
a Isolated yield.
b 30% of the substrate was recovered.
c NH4HCO3 was used instead of CO2.
d Partial conversion.
PZ3
O
N
N
H
H
N
N
MeCN
r.t.
PZ3
+
The highest yield was achieved in ethyl acetate (95%),
but the reaction time was relatively long (entry 4). The re-
action failed to occur in methanol, and all the starting ma-
terial was recovered after several days. Although the solu-
bility of iminophosphorane 1a in methanol was much low-
er than in the other tested solvents (~7 mg/mL), it should
have been sufficient for the reaction to proceed; the result
can therefore be attributed to the protic character of the
solvent. Aprotic solvents (tetrahydrofuran, dichlorometh-
ane, acetone, N,N-dimethylformamide, or toluene), other
than acetonitrile, all gave similar results. In an additional
experiment (entry 9), we used ammonium bicarbonate in-
stead of solid carbon dioxide. In this case, the reaction was
not very effective, and the desired product was accompa-
nied by several unidentified byproducts. Eventually, we
chose N,N-dimethylformamide (entry 5) as the best solvent
for the reaction with solid carbon dioxide. Subsequently, we
prepared a number of 1-aryl-2-benzimidazolones under
our optimized conditions (Figure 2).
Cl
Cl
Cl
Cl
1
5h
Entry
PZ3
PPh3
Iminophosphorane
Yielda (%)
1
2
3
4
5
1h
1s
90
92
51
P(NMe2)3
PBu3
1t
b
P(OMe)3
P(O-i-Pr)3
1u
1w
–
c
–
a Isolated yield.
b Multicomponent mixture.
c A rearrangement of 1 was observed.
In all the reactions, the conversion of the starting mate-
rial and the formation of products were evident by thin-lay-
er chromatography, but the iminophosphorane 1 could only
be isolated in three cases. We assume that iminophos-
phoranes formed from alkyl phosphites (entries 4 and 5)
are unstable and, consequently, cannot be isolated or un-
dergo rapid rearrangement. The idea then arose of combin-
ing two steps, the formation of 1 and its reaction with car-
The reaction appears to be compatible with either elec-
tron-withdrawing (CF3) or electron-donating (OR) substitu-
ents X and Y, as well as with heterocyclic groups (4-pyr-
idyl). All the reactions gave high or excellent yields. The re-
action was also insensitive to steric hindrance by
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

D
E. Łukasik, Z. Wróbel
Paper
Synthesis
H
H
N
H
N
H
N
H
N
H
N
F3C
N
O
O
O
O
O
O
N
N
N
Cl
N
N
N
Cl
Cl
Cl
OMe
I
I
Cl
OMe
Cl
Me
Me
2a (95%; 2 d)
2b (95%; 1 d)
2c (91%; 7 d)
2d (92%; 2 d)
2e (94% ;2 d)
2f (96%; 2 d)
H
N
H
N
H
N
H
N
H
N
H
N
F3C
F3C
O
O
O
O
O
O
N
N
N
N
N
N
Cl
Cl
F
MeO
OMe
OMe
Cl
F3C
Cl
OMe
Me
Br
2g (90%; 3 d)
2h (95%; 2 d)
2i (92%; 2 d)
2j (90%; 2 d)
2k (86%; 13 d)
2l (71%; 7 d)
N
H
H
N
H
N
H
N
H
N
H
N
F3C
N
O
O
O
O
OMe
O
O
N
N
N
N
N
N
Cl
MeO
N
N
OMe
N
Cl
2m (91%; 3 d)
OMe
2n (91%; 3 d)
2o (93%; 2 d)
2p (89%; 4 d)
2q (82%; 3 d)
2r (86% 2 d)
Figure 2 Synthesis of 1-arylbenzimidazol-2-ones 2a–r by the reactions of iminophosphoranes 1a–r with carbon dioxide
bon dioxide, in a one-pot system by mixing the phosphite
with carbon dioxide and converting the 2-nitrosoaniline di-
rectly into the target 2-benzimidazolone 2.
Table 3 One-Pot Synthesis of 2-Benzimidazolones 2 from N-Aryl-2-ni-
trosoanilines 5
PZ3, CO2
The high-yielding use of hexamethylphosphorous tri-
amide (HMPT; entry 2) had to be abandoned because of the
toxicity of the reagent. Trimethyl phosphite seemed to be
particularly suitable because of its low molecular mass, low
toxicity, and ready hydrolysis, which permits simple work-
up of the reaction mixture. Although trimethyl phosphite
was found to promote the reaction, the yields were general-
ly unsatisfactory (Table 3). A significant improvement in the
yield was achieved by using triisopropyl phosphite, which
is a little more expensive than trimethyl phosphite but re-
tains all its other merits. In this case, the unstable interme-
diate trialkyliminophosphorane was efficiently trapped by
carbon dioxide, protecting the former from possible rear-
rangement or decomposition.
5
2
DMF, r.t.
Entry
Producta
Z = OMe
Z = Oi-Pr
Time (d)
Yieldb (%)
Time (d)
Yieldb (%)
1
2
3
4
5
6
7
8
9
2c
2d
2e
2f
–
2
7
7
7
7
–
–
8
–
4
1
1
1
3
1
3
1
7
67
94
95
80
75
86
87
96
71
80
59
56
40
59
–
2g
2h
2l
2m
2r
–
The yields of the one-pot reaction of N-aryl-2-nitro-
soanilines with triisopropyl phosphite and carbon dioxide
were generally close to the combined yields of the two-step
process consisting of independent formation of 1 (Z = Ph)
50
a For structures, see Figure 2.
b Isolated yield.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

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E. Łukasik, Z. Wróbel
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Synthesis
followed by its reaction with carbon dioxide, as presented
in Figure 2. However, the one-pot procedure from 5 to 2,
employing cheap lightweight reagents, omitting laborious
isolation processes, and eliminating mass wastage, has con-
siderable advantages over the two-step method, particular-
ly in large-scale processing.
mixture was stirred at r.t. for the time specified in Table 3. When the
reaction was complete, the mixture was poured into H2O and extract-
ed with EtOAc. The organic phase was dried (Na2SO4) and concentrat-
ed, and the residue was purified by column chromatography [silica
gel, hexane–EtOAc (9:1 to 2:1)]. The yields are listed in Table 3.
6-Chloro-(4-chloro-2-iodophenyl)-1,3-dihydro-2H-benzimidazol-
In conclusion, we have developed a new and convenient
protocol for the synthesis of 1-arylbenzimidazol-2-ones by
a one-pot three-component reaction of N-aryl-2-nitrosoan-
ilines using solid carbon dioxide as the source of the car-
bonyl moiety. The high-yielding process is carried out un-
der mild conditions, i.e. ambient temperature and a rela-
tively low positive pressure, and is compatible with a
variety of aryl substituents. Furthermore, the atom econo-
my of the synthesis of the starting nitrosoanilines, accom-
plished by nucleophilic substitution of hydrogen, renders
the whole synthesis environmentally friendly, competing
strongly with other known procedures.
2-one (2a)
White solid; yield: 383 mg (95%); mp 275–277 °C.
IR (KBr): 3169, 3078, 1711, 1573, 1492 cm–1
1H NMR (400 MHz, DMSO-d6): δ = 6.63 (s, 1 H), 7.06–7.12 (m, 2 H),
7.56 (d, J = 8.3 Hz, 1 H), 7.67 (dd, J = 8.3, 2.2 Hz, 1 H), 8.15 (d, J = 2.2 Hz,
1 H), 11.31 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 101.1, 108.3, 110.3, 121.5, 125.1,
127.4, 129.8, 131.2, 131.6, 134.6, 135.7, 138.7, 152.7.
MS (EI): m/z (%) = 406 (44), 405 (10), 404 [M+] (69), 279 (65), 278 (22).
HRMS (EI): m/z calcd for C13H735Cl2IN2O: 403.8980; found: 403.8979.
.
6-Chloro-1-phenyl-1,3-dihydro-2H-benzimidazol-2-one (2b)18
White solid; yield: 232 mg (95%); mp 241–244 °C (Lit.18 238–240 °C).
IR (KBr): 3182, 1719, 1596, 1505, 1482 cm–1
1H NMR (400 MHz, DMSO-d6): δ = 6.91–6.96 (m, 1 H), 7.04–7.13 (m, 2
H), 7.42–7.62 (m, 5 H), 11.33 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 108.0, 110.3, 121.5, 125.1, 126.0,
127.4, 127.7, 129.5, 131.1, 134.0, 153.3.
MS (EI): m/z (%) = 246 (41), 245 (19), 244 [M+] (100), 217 (11), 215
(33).
.
1
Melting points of solid compounds are uncorrected. H and 13C NMR
spectra were recorded at 298 K on Varian Mercury 400 MHz and 500
MHz instruments and on a Varian VNMRS 600 MHz instrument.
Chemical shifts are expressed in ppm relative to TMS (1H NMR at 400,
500, or 600 MHz) or to the solvent used (13C NMR at 100, 125, and 150
MHz). Mass spectra were recorded on a GCT Premier spectrometer
(EI, 70 eV) or on a API 365i apparatus (ESI in MeOH). IR spectra were
recorded on a FT/IR Jasco 6200 spectrometer in KBr. Silica gel Merck
60 (230–400 mesh) was used for column chromatography. THF was
distilled from sodium/benzophenone ketyl before use. DMF was dried
over CaH2, distilled, and stored over MS.
HRMS (EI): m/z calcd for C13H935ClN2O: 244.0403; found: 244.0401.
1-(5-Chloro-2,4-dimethoxyphenyl)-5-(trifluoromethyl)-1,3-dihy-
dro-2H-benzimidazol-2-one (2c)
Common reagents and materials were purchased from commercial
sources and were used as received.
White solid; yield: 338 mg (91%); mp 250–252 °C.
IR (KBr): 3129, 3043, 2977, 1714, 1605, 1584 cm–1
.
Known N-aryl-2-nitrosoanilines 51–3 and 2-(arylamino)phenylimino-
phosphoranes 1a,d,e,g,q2 and 1f,h,i,j,p,r1 were prepared as described
previously. Preparations and characterizations of new 2-(arylami-
no)aryliminophosphoranes 1 and the starting N-aryl-2-nitrosoani-
lines 5 are described in the Supporting Information.
1H NMR (500 MHz, DMSO-d6): δ = 3.81 (s, 3 H), 4.00 (s, 3 H), 6.77 (d,
J = 8.5 Hz, 1 H), 7.00–7.04 (m, 1 H), 7.27–7.34 (m, 2 H), 7.52–7.58 (m,
1 H), 11.40 (s, 1 H).
13C NMR (125 MHz, DMSO-d6): δ = 56.3, 56.6, 98.5, 105.4 (d, JCF = 4
Hz), 108.4, 111.8, 114.3, 118.1 (d, JCF = 3.5 Hz), 121.9 (d, JCF = 32 Hz),
124.7 (d, JCF = 270 Hz), 128.6, 130.3, 134.0, 153.6, 155.4, 156.0.
Benzimidazol-2-ones 2 from Iminophosphoranes 1; General Pro-
cedure
MS (EI): m/z (%) = 374 (33), 372 [M+] (100), 353 (11), 329 (10).
A solution of the appropriate iminophosphorane 1a–r (1 mmol) in
anhyd DMF (10 mL) was placed in a glass ampoule equipped with a
Teflon stopcock and cooled to –65 °C. Solid CO2 (crushed dry ice; 200
mg, 4.5 mmol) was added in one portion. The ampule was sealed and
the mixture was stirred at r.t. for the time specified in Figure 2. When
the reaction was complete, the mixture was poured into H2O and ex-
tracted with EtOAc. The organic phase was dried (Na2SO4) and con-
centrated, and the residue was purified by column chromatography
[silica gel, hexane–EtOAc (9:1 to 2:1)]. The yields are listed in Figure 2.
HRMS (EI): m/z calcd for
372.0482.
C
16H1235ClF3N2O3: 372.0489; found:
6-Chloro-1-(2-iodo-4-methylphenyl)-1,3-dihydro-2H-benzimid-
azol-2-one (2d)
White solid; yield: 352 mg (92%); mp 251–253 °C.
IR (KBr): 3145, 1703, 1496, 1477 cm–1
1H NMR (400 MHz, DMSO-d6): δ = 2.38 (s, 3 H), 6.48–6.51 (m, 1 H),
.
7.06–7.08 (m, 2 H), 7.36–7.43 (m, 2 H), 7.90 (s, 1 H), 11.24 (s, 1 H).
One-Pot Synthesis of Benzimidazol-2-ones 1 from N-Aryl-2-nitro-
soarenes 5; General Procedure
13C NMR (100 MHz, DMSO-d6): δ = 20.1, 99.5, 108.0, 110.2, 121.2,
127.4, 129.9, 130.4, 131.5, 133.8, 139.9, 141.2, 152.9 (one signal miss-
ing).
MS (EI): m/z (%) = 386 (23), 385 (11), 384 [M+] (69), 259 (34), 257
(100).
A solution of the appropriate N-aryl-2-nitrosoaniline 5 (1 mmol) in
DMF (10 mL) was placed in a glass ampoule equipped with a Teflon
stopcock and cooled to –65 °C. Solid CO2 (crushed dry ice; 200 mg, 4.5
mmol) was added in one portion, followed by addition of trimethyl or
triisopropyl phosphite (3 mmol). The ampoule was sealed, and the
HRMS (EI): m/z calcd for C14H1035ClIN2O: 383.9526; found: 383.9519.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

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E. Łukasik, Z. Wróbel
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Synthesis
1-Phenyl-1,3-dihydro-2H-benzimidazol-2-one (2e)10,12d
13C NMR (100 MHz, DMSO-d6): δ = 55.4, 107.7, 110.1, 114.7, 121.1,
White solid; yield: 198 mg (94%); mp 207–208 °C [Lit.18 200–202 °C
125.0, 126.5, 127.3, 127.6, 131.7, 153.5, 158.5.
MS (EI): m/z (%) = 276 (33), 275 (16), 274 [M+] (100), 261 (18).
(benzene); Lit.12d 187–188 °C (hexane)].
IR (KBr): 3127, 3014, 1699, 1591, 1501, 1481 cm–1
.
HRMS (EI): m/z calcd for C14H1135ClN2O2: 274.0509; found: 274.0518.
1H NMR (500 MHz, DMSO-d6): δ = 7.04–7.06 (m, 2 H), 7.08–7.11 (m, 1
H), 7.15–7.17 (m, 1 H), 7.42–7.45 (m, 1 H), 7.56–7.58 (m, 4 H), 10.68
(s, 1 H).
13C NMR (125 MHz, DMSO-d6): δ = 108.8, 110.1, 121.5, 122.3, 126.3,
127.9, 128.1, 129.3, 130.5, 134.4, 155.2.
6-Fluoro-1-(4-tolyl)-1,3-dihydro-2H-benzimidazol-2-one (2j)
White solid; yield: 218 mg (90%); mp 253–255 °C.
IR (KBr): 3039, 3002, 1709, 1621, 1519, 1491 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 2.38 (s, 3 H), 6.74–6.79 (m, 1 H),
6.83–6.91 (m, 1 H), 7.01–7.07 (m, 1 H), 7.33–7.43 (m, 4 H), 11.13 (s, 1
H).
MS (EI): m/z (%) = 210 [M+] (100), 181 (34).
HRMS (EI): m/z calcd for C13H10N2O: 210.0793; found: 210.0797.
13C NMR (100 MHz, DMSO-d6): δ = 20.7, 96.3 (d, JCF = 29 Hz), 107.7 (d,
JCF = 24 Hz), 109.5 (d, JCF = 10 Hz), 124.7, 125.7, 129.9, 130.8 (d, JCF = 12
Hz), 131.5, 137.0, 153.7, 157.6 (d, JCF = 233 Hz).
6-Chloro-1-(4-tolyl)-1,3-dihydro-2H-benzimidazol-2-one (2f).
White solid; yield: 248 mg (96%); mp 226–229 °C.
MS (EI): m/z (%) = 242 [M+] (100), 241 (11), 199 (14).
IR (KBr): 3036, 1700, 1520, 1484 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 2.38 (s, 3 H), 6.87–6.90 (m, 1 H),
HRMS (EI): m/z calcd for C14H11FN2O: 242.0855; found: 242.0852.
7.04–7.10 (m, 2 H), 7.33–7.41 (m, 4 H), 11.26 (s, 1 H).
1-[2-Methoxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-
13C NMR (100 MHz, DMSO-d6): δ = 20.7, 107.9, 110.2, 121.3, 125.0,
125.9, 127.3, 129.9, 131.4, 137.2, 153.3 (one signal missing).
MS (EI): m/z (%) = 260 (33), 259 (19), 258 [M+] (100), 215 (10).
HRMS (EI): m/z calcd for C14H1135ClN2O: 258.0560; found: 258.0565.
1,3-dihydro-2H-benzimidazol-2-one (2k)19
White solid; yield: 323 mg (86%); mp 229–231 °C (Lit.19 226 °C).
IR (KBr): 3138, 1718, 1524, 1448 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 3.86 (s, 3 H), 6.81 (d, J = 8.0 Hz, 1
H), 7.29–7.38 (m, 2 H), 7.46–7.53 (m, 1 H), 7.87–7.96 (m, 2 H), 11.52
(s, 1 H).
1-(4-Bromophenyl)-6-methoxy-1,3-dihydro-2H-benzimidazol-2-
one (2g).
13C NMR (125 MHz, DMSO-d6): δ = 56.8, 106.0 (d, JCF = 3 Hz), 109.2,
114.0, 118.6 (d, JCF = 3 Hz), 121.4 (d, JCF = 39 Hz), 121.9 (JCF = 32 Hz),
122.7, 124.4 (d, JCF = 272 Hz), 124.8 (JCF = 271 Hz), 127.7 (d, JCF = 4 Hz),
128.3 (d, JCF = 3 Hz), 129.2, 133.9, 153.9, 158.5.
White solid; yield: 286 mg (90%); mp 202–204 °C.
IR (KBr): 3170, 3070, 1702, 1616, 1492, 1387 cm–1
1H NMR (400 MHz, DMSO-d6): δ = 3.69 (s, 3 H), 6.59 (d, J = 2.2 Hz, 1
H), 6.66 (dd, J = 8.3, 2.2 Hz, 1 H), 6.97 (d, J = 8.3 Hz, 1 H), 7.48–7.55 (m,
2 H), 7.70–7.76 (m, 2 H), 10.97 (s, 1 H).
.
MS (EI): m/z (%) = 376 [M+] (100), 359 (22), 346 (26), 319 (38).
HRMS (EI): m/z calcd for C16H10F6N2O2: 376.0646; found: 376.0662.
13C NMR (100 MHz, DMSO-d6): δ = 55.6, 95.1, 107.7, 109.6, 119.8,
122.2, 127.8, 130.3, 132.3, 133.9, 153.4, 154.7.
MS (EI): m/z (%) = 320 (15), 319 (94), 318 [M+] (24), 317 (100), 223
(10).
1-(5-Chloro-2-methoxyphenyl)-5-(trifluoromethyl)-1,3-dihydro-
2H-benzimidazol-2-one (2l)14a
White solid; yield: 243 mg (71%); mp 225–227 °C (Lit.14a 135–138 °C).
HRMS (EI): m/z calcd for C14H1179BrN2O2: 318.0004; found: 318.0015.
IR (KBr): 3139, 3046, 1714, 1634, 1595, 1505, 1483 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 3.76 (s, 3 H), 6.80 (d, J = 8.5 Hz, 1
H), 7.29–7.35 (m, 3 H), 7.56–7.62 (m, 2 H), 11.48 (s, 1 H).
13C NMR (125 MHz, DMSO-d6): δ = 56.1, 105.5 (d, JCF = 3.5 Hz), 108.7,
114.4, 118.2 (d, JCF = 4 Hz), 122.0 (d, JCF = 32 Hz), 122.8, 124.0, 124.7 (d,
JCF = 269 Hz), 128.7, 129.6, 130.1, 133.4, 153.3, 154.2.
6-Chloro-1-(4-chlorophenyl)-1,3-dihydro-2H-benzimidazol-2-one
(2h)18
White solid; yield: 264 mg (95%); mp 243–245 °C [Lit.18 235–237 °C
(aq. EtOH)].
IR (KBr): 3040, 1746, 1719, 1499, 1482 cm–1
.
MS (EI): m/z (%) = 344 (33), 343 (18), 342 [M+] (100), 325 (19), 323
(17).
1H NMR (400 MHz, DMSO-d6): δ = 6.91–7.20 (m, 3 H), 7.47–7.75 (m, 4
H), 11.33 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 108.1, 110.3, 121.6, 125.1, 127.4,
127.7, 129.5, 130.8, 131.9, 132.9, 153.1.
HRMS (EI): m/z calcd for
C
15H1035ClF3N2O2: 342.0383; found:
342.0393.
MS (EI): m/z (%) = 280 (65), 279 (16), 278 [M+] (100).
HRMS (EI): m/z calcd for C13H835Cl2N2O: 278.0014; found: 278.0021.
1-(4-Chlorophenyl)-5-(trifluoromethyl)-1,3-dihydro-2H-benzim-
idazol-2-one (2m)
White solid; yield: 284 mg (91%); mp 212–215 °C.
6-Chloro-1-(4-methoxyphenyl)-1,3-dihydro-2H-benzimidazol-2-
IR (KBr): 3139, 3038, 1730, 1636, 1498 cm–1
.
one (2i)15e,18
1H NMR (600 MHz, DMSO-d6): δ = 7.16 (d, J = 8.3 Hz, 1 H), 7.33–7.39
(m, 2 H), 7.59–7.66 (m, 4 H), 11.58 (s, 1 H).
13C NMR (150 MHz, DMSO-d6): δ = 105.6, 105.7 (d, JCF = 4 Hz), 108.6,
118.3 (d, JCF = 4 Hz), 122.4 (d, JCF = 32 Hz), 124.6 (d, JCF = 270 Hz),
127.9, 128.7, 129.5, 132.2, 132.8 (d, JCF = 3 Hz), 153.2.
White solid; yield: 252 mg (92%); mp 252–254 °C (Lit.18 252–253 °C).
IR (KBr): 3040, 1703, 1519, 1484, 1393 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 3.82 (s, 3 H), 6.82–6.87 (m, 1 H),
7.03–7.15 (m, 4 H), 7.39–7.46 (m, 2 H), 11.22 (s, 1 H).
MS (EI): m/z (%) = 314 (33), 313 (16), 312 [M+] (100), 249 (21).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

G
E. Łukasik, Z. Wróbel
Paper
Synthesis
HRMS (EI): m/z calcd for C14H835ClF3N2O: 312.0277; found: 312.0269.
IR (KBr): 3185, 1733, 1589, 1507, 1485 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 6.99–7.39 (m, 3 H), 7.55–7.83 (m, 2
H), 8.60–8.88 (m, 2 H), 11.49 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 109.0, 110.6, 119.2, 122.4, 125.3,
127.7, 129.4, 141.7, 151.0, 152.6.
MS (EI): m/z (%) = 247 (39), 246 (18), 245 [M+] (100), 216 (18).
HRMS (EI): m/z calcd for C12H835ClN3O: 245.0356; found: 245.0359.
1-(2,4-Dimethoxyphenyl)-1,3-dihydro-2H-benzimidazol-2-one
(2n)13b
White solid; yield: 246 mg (91%); mp 210–213 °C.
IR (KBr): 3136, 3061, 1712, 1693, 1610, 1519 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 3.71 (s, 3 H), 3.84 (s, 3 H), 6.52 (d,
J = 7.6 Hz, 1 H), 6.65 (dd, J = 8.6, 2.2 Hz, 1 H), 6.78 (d, J = 2.2 Hz, 1 H),
6.89–6.95 (m, 1 H), 6.96–7.05 (m, 2 H), 7.26 (d, J = 8.6 Hz, 1 H), 10.93
(s, 1 H).
Acknowledgment
13C NMR (100 MHz, DMSO-d6): δ = 55.6, 55.7, 99.6, 105.3, 108.1,
This research was supported by the Polish National Centre of Science
(NCN), Research Grant UMO-2014/13/N/ST5/03423.
108.8, 115.2, 120.6, 121.1, 128.4, 130.5, 131.5, 153.7, 156.4, 160.7.
MS (EI): m/z (%) = 270 [M+] (100), 255 (21), 253 (22).
HRMS (EI): m/z calcd for C15H14N2O3: 270.1004; found: 270.1000.
Supporting Information
1-(3-Methoxyphenyl)-1,3-dihydro-2H-benzimidazol-2-one (2o)
Supporting information for this article is available online at
White solid; yield: 223 mg (93%); mp 136–139 °C.
http://dx.doi.org/10.1055/s-0035-1561301.
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IR (KBr): 3010, 1701, 1603, 1582, 1497 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 3.80 (s, 3 H), 6.95–7.15 (m, 7 H),
7.43–7.52 (m, 1 H), 11.14 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 55.4, 108.3, 109.1, 111.7, 113.1,
References
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118.0, 120.9, 121.8, 128.4, 130.0, 130.1, 135.7, 153.1, 159.9.
MS (EI): m/z (%) = 240 [M+] (100), 198 (10), 181 (13).
HRMS (EI): m/z calcd for C14H12N2O2: 240.0899; found: 240.0908.
3-(2,6-Dimethylphenyl)-5-methoxy-1,3-dihydro-2H-imidazo[4,5-
h]quinolin-2-one (2p)
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Sum, Y. N.; Zhang, Y. Green Chem. 2013, 15, 2086.
Yellow solid; yield: 284 mg (89%); mp >270 °C.
IR (KBr): 3000, 1694, 1633, 1597, 1523, 1489 cm–1
.
1H NMR (600 MHz, F3CCO2D): δ = 2.10 (s, 6 H), 4.08 (s, 3 H), 6.81 (s, 1
H), 7.40 (d, J = 7.8 Hz, 2 H), 7.52 (t, J = 7.8 Hz, 1 H), 7.90–8.00 (m, 1 H),
9.03 (d, J = 5.4 Hz, 1 H), 9.63 (d, J = 8.4 Hz, 1 H) (N–H proton was not
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13C NMR (150 MHz, F3CCO2D): δ = 18.2, 58.6, 95.1, 110.3, 120.5, 122.6,
127.4, 130.6, 131.8, 133.9, 138.5, 139.5, 145.4, 147.3, 157.4, 157.5.
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HRMS (EI): m/z calcd for C19H17N3O2: 319.1312; found: 319.1324.
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1-{2-[(4-Methylpiperazin-1-yl)methyl]phenyl}-1,3-dihydro-2H-
benzimidazol-2-one (2q)
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White solid; yield: 264 mg (82%); mp 163–166 °C.
IR (KBr): 3062, 2679, 1703, 1619, 1499 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 1.83–2.17 (m, 11 H), 3.23 (d, J =
12.0 Hz, 1 H), 3.45 (d, J = 12.0 Hz, 1 H), 6.54 (d, J = 8.0 Hz, 1 H), 6.92 (t,
J = 8.0 Hz, 1 H), 6.99–7.09 (m, 2 H), 7.34–7.57 (m, 4 H), 11.01 (s, 1 H).
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120.5, 121.1, 128.0, 128.6, 128.7, 129.1, 130.5, 131.5, 133.3, 136.9,
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(35).
HRMS (EI): m/z calcd for C19H22N4O: 322.1794; found: 322.1809.
6-Chloro-1-pyridin-4-yl-1,3-dihydro-2H-benzimidazol-2-one (2r)
White solid; yield: 211 mg (86%); mp 270–272 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H

H
E. Łukasik, Z. Wróbel
Paper
Synthesis
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H