A Convenient Synthesis of Amidines via Cycloaddition-Decarboxylation of Isocyanates and Nitrones

Article abstract of DOI:10.1055/s-0040-1707989

A base-promoted reaction between isocyanates and nitrones has been described, allowing an access to a variety of important functionalized amidines under mild reaction conditions. This strategy provides a convenient, effective, and scalable approach for the direct assembly of amidine compounds from simple starting materials in excellent yields.

Full text of DOI:10.1055/s-0040-1707989

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2020, 52, 1773–1778
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Y. Wu et al.
Paper
Synthesis
A Convenient Synthesis of Amidines via Cycloaddition–
Decarboxylation of Isocyanates and Nitrones
Yijing Wu
R
O
Xinyi Chen
O
N
C
1) CH2Cl2, 9 h, rt
N
N
Ar2
Mei-Mei Zhang*
Ar1
+
R
Ar2
NH
Ar1
2) Cs2CO3, EtOH, 30 min
H
School of Chemistry and Materials Science, Jiangsu Key
Laboratory of Green Synthesis for Functional Materials,
Jiangsu Normal University, Xuzhou, Jiangsu 221116,
P. R. of China
Easy to operate
Mild reaction conditions
High efficiency, 71–91% yield
Broad substrate scope, 17 examples
mmzhangwtt@163.com
a) Representative disadvatanges of nitriles, amides, etc. to amidines
Received: 07.01.2020
Accepted after revision: 17.02.2020
Published online: 09.03.2020
DOI: 10.1055/s-0040-1707989; Art ID: ss-2020-f0073-op
O
R1
R
CN
R
N
H
Preactivation of substrates
Multistep reactions, not easy to operate
Abstract A base-promoted reaction between isocyanates and ni-
trones has been described, allowing an access to a variety of important
functionalized amidines under mild reaction conditions. This strategy
provides a convenient, effective, and scalable approach for the direct
assembly of amidine compounds from simple starting materials in ex-
cellent yields.
Use of special catalysts or some unfriendly chemicals
Strict anhydrous conditions
b) [3+2] cycloaddition reactions between isocyanates and nitrones
O
O
CH2Cl2
O
N
Ph
+
N
Ph
Ph
N
C
O
Ph
N
Overnight, rt
Ph
H
Ph
Key words amidines, isocyanates, nitrone, heterocycles, decarboxyl-
ation
Well-established
c) Anderson's work: mild conditons and one-step method
Amidines constitute an important class of versatile
building blocks used in the synthesis of heterocyclic and
alicyclic compounds,1,2 catalysis, materials science, phar-
maceutical chemistry, and organic synthesis.3 Thus far, re-
markable advances in the development of new synthetic
methods for such valuable motifs have been witnessed.4
Compared to these developed protocols, the most attractive
routes to these compounds are starting from basic chemi-
cals along with mild-reaction conditions and high efficien-
cy.5 Notably, these simple materials include nitriles,6 am-
ides,7 carbodiimides,8 amidines,9 etc.10 However, many of
the reported synthetic protocols suffer from a number of
shortcomings, such as employment of special catalysts, ne-
cessity for strict reaction conditions, multistep nature of
the reactions, or low yield (Scheme 1a). Thus, operationally
simple methods for the direct assembly of amidines from
commercially available materials under mild reaction con-
ditions are highly desired.
Ph
N
O
Ph
N
Ph
N
C
O
Ph
Ph
N
Ph
Ph
toluene, 18 h
Ph
Elaborately designed substrates
d) This work: one-pot without isolation
Ph
N
O
1) CH2Cl2, 9 h, rt
N
Ph
+
Ph
N C O
Ph
Ph
NH
Ph
2) Cs2CO3, 30 min
H
Easy to operate
General substrates
Scalable
Scheme 1 Reaction between isocyanates and nitrones to amidines
trones as substrates.12 This reaction allows access to an ini-
tial oxadiazolidinone intermediate, which then undergoes
extrusion of CO2 and styrenyl migration to provide a series
of functionalized amidine products (Scheme 1c). However,
this synthetic method largely relies on elaborately designed
substrates that are not readily accessible. Herein, we report
a base-promoted cycloaddition–decarboxylation of isocya-
nates and nitrones at ambient temperature, providing a
convenient and practical approach for the direct assembly
of various amidines in high yields (Scheme 1d).
Oxadiazolidinones can be accessed through a well-es-
tablished [3+2]-cycloaddition reaction between isocyanates
and nitrones in nearly quantitative yields (Scheme 1b).11 In
2014, Anderson and co-workers developed a modular route
to N-styrenylamidines by using N-aryl-,-unsaturated ni-
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Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

1774
Y. Wu et al.
Paper
Synthesis
O
1) CH2Cl2, 9 h, rt
R
R
N
Ar2
Ar1
+
N C
O
N
2) Cs2CO3 (2 equiv)
EtOH, rt, 30 min
H
Ar2
NH
Ar1
1
2
3
residual water
Scope with respect to nitrones
PBP
N
PBP
N
PBP
Ph
N
PBP
N
Ph
NH
Me
Ph
NH
NH
Cl
Ph
NH
Me
OMe
3b, 78%
3c, 84%
3d, 81%
3e, 89%
PBP
N
PBP
PBP
PBP
N
N
N
NH
Ph
NH
Ph
NH
Ph
NH
Ph
Me
Cl
Br
Cl
3f, 73%
3g, 82%
3h, 87%
3i, 89%
PBP
PBP
PBP
N
N
N
NH
Ph
NH
Ph
NH
Ph
MeO
Cl
Br
3j, 91%
Scope with respect to isocyanates
3k, 71%
3l, 83%
Cl
F3C
F3CO
N
Me
N
N
N
N
Ph
NH
Ph
Ph
3n, 88%
NH
Ph
Ph
3o, 86%
NH
Ph
Ph
3p, 90%
NH
Ph
Ph
3q, 87%
NH
Ph
3m, 85%
Scheme 2 Synthesis of amidines through CO2 extrusion. All reactions were carried out with 1 (0.5 mmol), 2 (0.55 mmol), and Cs2CO3 (2 equiv) in EtOH
(2.0 mL) at rt under air for 30 min. Yields of isolated products 3 after purification by column chromatography are shown.
Initially, N-benzylideneaniline oxide (1a) and 1-bromo-
4-isocyanatobenzene (2a) were selected as model sub-
strates to start our investigation, which failed to produce
the decarboxylated product N′-(4-bromophenyl)-N-phenyl-
benzimidamide (3a, PBP = 4-BrC6H4) even if extending the
reaction time to 24 hours (Table 1, entry 1). Intriguingly,
addition of base (KOtBu, 2.0 equiv) to the reaction mixture
triggered extrusion of CO2 and provided amidine 3a in 36%
yield (entry 2). Encouraged by these findings, a survey of
bases including K2CO3, Cs2CO3, DBU, and DABCO were pur-
sued to further examination of the reaction conditions (en-
tries 2–6). Cs2CO3 displayed the highest reactivity to pro-
vide the desired product 3a with an improved yield of 46%
(entry 4). Next, changing the solvent to EtOH greatly in-
creased the yield of 3a to 78% and 93% (entries 9 and 10),
while aprotic polar solvents, such as DCE and MeCN, had a
negative effect on the reaction and delivered 3a in dimin-
ished yields (entries 7 and 8). The reaction temperature had
only a negligible effect on the reaction outcome (entries 11
and 12), thereby allowing for extrusion of CO2 under ambi-
ent temperature. Decreasing the amount of base to 1.0 and
0.5 equivalent afforded 3a in drastically reduced yields (en-
tries 13 and 14). Therefore, use of 2.0 equivalents of Cs2CO3
in EtOH at room temperature (entry 12) was selected as the
optimal reaction conditions.
With the optimized reaction conditions in hand, gener-
ality of the developed protocol was investigated with a vari-
ety of aryl isocyanates and nitrones as substrates (Scheme
Ph
O
N
Standard
conditions
PBP
Ph
Br
N
PhI(OAc)2 (3 equiv)
MeCN, 120 °C, 1 h
N
Ph
Ph
Ph
PBP
N C O
+
N
NH
Ph
H
1a
2a
[22 mmol]
4, 57%
3a
[20 mmol]
[5.88 g, 84%]
Large scale through filtration in slightly decreasing yield
Scheme 3 Gram-scale synthesis and further derivatization. Reagents and conditions: 3a (0.3 mmol), PhI(OAc)2 (0.9 mmol), MeCN (3 mL), 120 °C, 1 h.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, 1773–1778

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Y. Wu et al.
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Synthesis
Table 1 Optimization of the Reaction Conditionsa
To gain insight into the reaction mechanism, the pro-
posed cyclic intermediate oxadiazolidinone 5a was synthe-
sized and subjected to the optimized reaction conditions,
providing the expected product 3a in 92% yield (Scheme
4a). This implies that oxadiazolidinone is the key interme-
diate in this reaction. Based on the experimental observa-
tions and related literature precedents,14 a plausible reac-
tion mechanism is proposed (Scheme 4b). First, nitrone 1
and isocyanate 2 undergoes a [3+2] cycloaddition to furnish
oxadiazolidinone intermediate 5. Then, the intramolecular
nucleophilic attack of nitrogen to carbonyl carbon results in
the ring intermediate 6. A ring opening promoted by addi-
tion of a hydroxyl anion results in the formation of inter-
mediate 7. Following, 7 undergoes a decarboxylation–pro-
tonation sequence to form the intermediate 8, which subse-
quently eliminates water to form the final product 3. The
residual water present in the solvent or air is sufficient to
ensure the completion of the reaction.
PBP
Ph
1) CH2Cl2, 9 h, rt
O
N
+
Ph
Br
N C O
N
Ph
NH
Ph
2) base (2 equiv), solvent,
temp, 30 min
H
2a
1a
3a
PBP = 4-BrC6H4
Entry
Base
–
Solvent
Temp (°C)
Yield (%)b
1c
2
toluene
toluene
toluene
toluene
toluene
toluene
DCE
80
80
80
80
80
80
80
80
80
80
40
rt
0
36
28
46
0
KOtBu
3
K2CO3
4
Cs2CO3
DBU
5
6
DABCO
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
0
7
47
39
93
78
91
90
31
17
8
MeCN
EtOH
9d
10e
11d
12d
13d,f
14d,g
EtOH
a) Mechanistic investigations
EtOH
O
Ph
EtOH
Cs2CO3 (2 equiv)
O
N
HN
N
N
Br
EtOH
rt
EtOH, rt, 30 min
residual water
Ph
Ph
Br
Ph
EtOH
rt
5a
3a, 92%
a Reaction conditions: 1a (0.5 mmol), 2a (0.55 mmol), and base (2.0 equiv)
in solvent (2.0 mL) under air for 30 min.
b Yield of isolated product 3a after chromatographic purification.
c Reaction time: 24 h.
b) Plausible mechanism for amidines synthesis
d Absolute EtOH.
O
Ph
N
Ph
Ph
O
N
Ph
N C O
2
e EtOH 95% was used.
O
N
Ph
O
N
Ph
N
f Cs2CO3: 1 equiv.
Ph
Ph
O
OH
g Cs2CO3: 0.5 equiv.
H
Ph
6
1
5
Ph
O
O
Ph
OH
N
HO
Ph
N
H
N
H
N
N
Ph
Ph
Ph
NH
Ph
– CO2
– H2O
Ph
2). A collection of diversely functionalized aryl nitrones and
isocyanates delivered the expected amidine products 3 in
excellent yields. Aryl nitrones bearing electron-donating or
electron-withdrawing moieties at the para-, ortho-, and
meta-positions of the arene moieties reacted with 1-bro-
mo-4-isocyanatobenzene (2a) to produce the correspond-
ing products 3a–j in high yields. Similarly, substrate with a
disubstituted aryl moiety was also well-tolerated, affording
the product 3k in 71% yield. A nitrone with a fused aromatic
ring (1-naphthyl) was also evaluated, delivering the corre-
sponding adduct 3l in 83% yield. Furthermore, the protocol
also tolerated a variety of substituents on the arene ring of
the isocyanate (2b–f), efficiently delivering a set of diverse
N′-aryl-N-phenylbenzimidamides 3m–q in high yields. Re-
grettably, aliphatic isocyanates or aliphatic nitrones were
unable to afford prospective products.
Ph
3
8
7
Scheme 4 Proposed reaction mechanism
In summary, we have developed a base-promoted pro-
tocol for cycloaddition–decarboxylation of the isocyanates
with nitrones at ambient temperature, providing a conve-
nient approach for direct assembly of amidine scaffolds.
Melting points were determined in open capillaries and are uncor-
rected. 1H and 13C NMR spectra were obtained on solutions in CDCl3,
acetone-d6 or CDCl3 + D2SO4 with Me4Si as internal standard, using a
Bruker 400 spectrometer. HRMS analyses were carried out using a
Bruker micrOTOF-Q-MS analyzer. All chemicals were obtained from
Beijing InnoChem Science & Technology Co., Ltd, except for EtOH,
which was purchased from Sinopharm Chemical.
Subsequently, the established methodology was applied
to synthesis of amidine 3a on a 20 mmol scale (Scheme 3),
delivering the expected product in 84% yield (5.88 g). Fur-
thermore, amidine 3a was also successfully converted to
benzimidazole 4a through an oxidative annulation using
PhI(OAc)2 as the chemical oxidant.13
N′-Aryl-N-arylbenzimidamide Derivatives 3;N′-(4-Bromophenyl)-
N-phenylbenzimidamide (3a); Typical Procedure
In a 10 mL round-bottomed flask, a mixture of 1a (98 mg, 0.5 mmol)
and 2a (108 mg, 0.55 mmol) in CH2Cl2 (2.0 mL) was stirred overnight
at rt until the substrate 1a was consumed as indicated by TLC (ca. 9
h). The resulting reaction was concentrated in vacuo. To the residue
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Y. Wu et al.
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Synthesis
were added Cs2CO3 (325 mg, 1 mmol, 2.0 equiv) and EtOH (2.0 mL)
and the mixture was stirred at rt, until only one spot was indicated in
TLC (ca. 30 min). The resulting mixture was concentrated, and the
residue was taken up in CH2Cl2. The organic layer was washed with
brine, dried (MgSO4), and concentrated. Purification of the crude
product by column chromatography (silica gel; PE/EtOAc 10:3) afford-
ed 3a as a white solid; yield: 157 mg (90%); mp 123–124 °C.
N′-(4-Bromophenyl)-3-chloro-N-phenylbenzimidamide (3f)
Yield: 141 mg (73%); white solid; mp 123–124 °C.
1H NMR (400 MHz, acetone-d6):  = 8.45 (s, 1 H), 7.94 (s, 2 H), 7.45–
7.23 (m, 7 H), 6.90–6.63 (m, 4 H).
13C NMR (100 MHz, acetone-d6):  = 153.82, 150.42, 141.53, 137.63,
134.43, 132.10, 130.62, 130.03, 129.62, 129.27, 128.35, 125.24,
123.11, 122.17, 120.49.
HRMS (ESI-TOF): m/z calcd for C19H1579Br35ClN2 [M + H]+: 385.0102;
found: 385.0107.
If the reactions are performed on a large scale, it is easy to isolate the
product by filtration, albeit in slightly reduced yield.
1H NMR (400 MHz, CDCl3 + D2SO4):  = 7.40–7.33 (m, 1 H), 7.26–7.18
(m, 3 H), 7.14 (d, J = 8.7 Hz, 1 H), 7.09–7.03 (m, 4 H), 6.98–6.89 (m, 3
H), 6.87–6.77 (m, 2 H).
N′-(4-Bromophenyl)-4-chloro-N-phenylbenzimidamide (3g)
Yield: 157 mg (82%); white solid; mp 161–162 °C.
1H NMR (400 MHz, acetone-d6):  = 8.49 (s, 1 H), 8.00–7.91 (m, 2 H),
13C NMR (100 MHz, CDCl3 + D2SO4):  = 135.56, 134.96, 132.44,
132.08, 130.47, 129.20, 129.03, 127.10, 126.81, 125.29, 120.60.
7.34–6.71 (m, 11 H).
HRMS (ESI-TOF): m/z calcd for C19H1679BrN2 [M + H]+: 351.0491;
13C NMR (100 MHz, acetone-d6):  = 153.88, 149.92, 141.21, 135.65,
133.22, 131.29, 130.73, 128.46, 128.26, 123.87, 122.30, 120.08,
113.77.
HRMS (ESI-TOF): m/z calcd for C19H1579Br35ClN2 [M + H]+: 385.0102;
found: 385.0115.
found: 351.0507.
N′-(4-Bromophenyl)-N-(p-tolyl)benzimidamide (3b)
Yield: 142 mg (78%); white solid; mp 101–102 °C.
1H NMR (400 MHz, acetone-d6):  = 8.33 (s, 1 H), 7.81 (s, 2 H), 7.38–
6.58 (m, 11 H), 2.24 (s, 3 H).
4-Bromo-N′-(4-bromophenyl)-N-phenylbenzimidamide (3h)
13C NMR (100 MHz, acetone-d6):  = 155.26, 150.54, 138.79, 135.11,
131.15, 129.15, 128.89, 128.87, 128.11, 124.42, 122.37, 119.75,
112.06, 20.89.
Yield: 186 mg (87%); white solid; mp 177–178 °C.
1H NMR (400 MHz, CDCl3):  = 7.48–7.37 (m, 4 H), 7.25–7.15 (m, 6 H),
7.00–6.89 (m, 2 H), 6.68–6.38 (m, 2 H).
HRMS (ESI-TOF): m/z calcd for C20H1879BrN2 [M + H]+: 365.0648;
found: 365.0641.
13C NMR (100 MHz, CDCl3):  = 153.3, 133.3, 132.7, 131.9, 131.6,
130.7, 130.1, 129.8, 129.0, 128.9, 124.0, 123.9, 123.6, 123.1, 123.0,
122.3, 121.4, 121.1, 120.6, 120.1, 114.9.
HRMS (ESI-TOF): m/z calcd for C19H1579Br2N2 [M + H]+: 428.9597;
found: 428.9606.
N′-(4-Bromophenyl)-N-(o-tolyl)benzimidamide (3c)
Yield: 153 mg (84%); white solid; mp 110–111 °C.
1H NMR (400 MHz, CDCl3 + D2SO4):  = 13.12–11.95 (m, 1 H), 7.39–
7.32 (m, 1 H), 7.25–7.14 (m, 6 H), 7.10 (d, J = 7.4 Hz, 1 H), 7.05 (t, J =
7.3 Hz, 1 H), 6.91–6.78 (m, 4 H), 2.40 (s, 3 H).
N′-(4-Bromophenyl)-4-methyl-N-phenylbenzimidamide (3i)
Yield: 162 mg (89%); white solid; mp 121–122 °C.
13C NMR (100 MHz, CDCl3 + D2SO4):  = 164.05, 135.24, 134.49,
134.31, 132.33, 132.09, 130.87, 130.09, 128.99, 127.98, 127.90,
126.61, 126.41, 125.71, 120.44, 18.25.
HRMS (ESI-TOF): m/z calcd for C20H1879BrN2 [M + H]+: 365.0648;
found: 365.0655.
1H NMR (400 MHz, CDCl3 + D2SO4):  = 7.27 (d, J = 8.6 Hz, 1 H), 7.23–
7.14 (m, 4 H), 7.08 (d, J = 8.0 Hz, 2 H), 7.05–6.94 (m, 2 H), 6.87 (d, J =
8.6 Hz, 1 H), 2.34 (s, 3 H).
13C NMR (100 MHz, CDCl3 + D2SO4):  = 163.51, 144.00, 132.34,
130.60, 130.11, 129.27, 127.41, 126.67, 126.63, 125.16, 125.12,
121.58, 120.98, 21.73.
N′-(4-Bromophenyl)-N-(4-methoxyphenyl)benzimidamide (3d)
HRMS (ESI-TOF): m/z calcd for C20H1879BrN2 [M + H]+: 365.0648;
found: 365.0657.
Yield: 154 mg (81%); white solid; mp 119–120 °C.
1H NMR (400 MHz, acetone-d6):  = 8.26 (s, 1 H), 8.02–7.89 (m, 2 H),
7.42–7.21 (m, 7 H), 6.88–6.57 (m, 4 H), 3.76 (s, 3 H).
13C NMR (100 MHz, acetone-d6):  = 155.93, 150.33, 135.99, 131.97,
129.97, 129.74, 128.96, 125.38, 123.98, 122.09, 114.42, 56.69.
HRMS (ESI-TOF): m/z calcd for C20H1879BrN2O [M + H]+: 381.0597;
N′-(4-Bromophenyl)-4-methoxy-N-phenylbenzimidamide (3j)
Yield: 173 mg (91%); white solid; mp 117–118 °C.
1H NMR (400 MHz, acetone-d6):  = 8.31 (m, 1 H), 8.13–7.91 (m, 2 H),
7.39–6.61 (m, 11 H), 3.77 (s, 3 H).
13C NMR (100 MHz, acetone-d6):  = 161.23, 154.40, 150.64, 141.43,
found: 381.0588.
131.18, 130.54, 128.36, 127.49, 124.94, 123.02, 120.07, 113.37, 54.74.
HRMS (ESI-TOF): m/z calcd for C20H1879BrN2O [M + H]+: 381.0597;
found: 381.0593.
N′-(4-Bromophenyl)-N-(4-chlorophenyl)benzimidamide (3e)
Yield: 171 mg (89%); white solid; mp 125–126 °C.
1H NMR (400 MHz, acetone-d6):  = 8.54 (s, 1 H), 7.97 (s, 2 H), 7.43–
7.07 (m, 9 H), 6.62 (m, 2 H).
2-Bromo-N′-(4-bromophenyl)-4-chloro-N-phenylbenzimidamide
(3k)
13C NMR (100 MHz, acetone-d6):  = 155.36, 148.66, 140.24, 135.39,
131.35, 130.07, 128.97, 128.39, 128.33, 126.41, 124.21, 121.89,
114.00.
HRMS (ESI-TOF): m/z calcd for C19H1579BrClN2 [M + H]+: 385.0102;
found: 385.0118.
Yield: 164 mg (71%); white solid; mp 102–103 °C.
1H NMR (400 MHz, acetone-d6):  = 8.47 (s, 1 H), 7.92 (s, 2 H), 7.62 (d,
J = 2.0 Hz, 1 H), 7.44–6.80 (m, 9 H).
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13C NMR (100 MHz, acetone-d6):  = 152.19, 149.46, 140.09, 136.89,
135.01, 132.53, 131.30, 128.51, 127.49, 124.15, 122.50, 121.99,
121.18, 119.57, 114.20.
13C NMR (100 MHz, CDCl3 + D2SO4):  = 162.24, 139.94, 136.24,
132.50, 130.12, 129.45, 128.93, 128.08, 127.76, 126.68, 126.14,
126.00, 125.97, 125.00, 124.59, 122.36.
HRMS (ESI-TOF): m/z calcd for C19H1479Br235ClN2 [M + H]+: 462.9207;
HRMS (ESI-TOF): m/z calcd for C20H16F3N2 [M + H]+: 341.1260; found:
found: 462.9214.
341.1277.
N′-(4-Bromophenyl)-N-phenyl-1-naphthimidamide (3l)
N-Phenyl-N′-[4-(trifluoromethoxy)phenyl]benzimidamide (3q)
Yield: 166 mg (83%); white solid; mp 162–163 °C.
Yield: 155 mg (87%); white solid; mp 82–84 °C.
1H NMR (400 MHz, CDCl3 + D2SO4):  = 14.72 (br s, 1 H), 8.01–7.89 (m,
2 H), 7.88–7.81 (m, 1 H), 7.56–7.48 (m, 2 H), 7.48–7.39 (m, 2 H), 7.07
(d, J = 8.7 Hz, 2 H), 7.02–6.92 (m, 3 H), 6.92–6.81 (m, 2 H), 6.75 (d, J =
8.5 Hz, 2 H).
13C NMR (100 MHz, CDCl3 + D2SO4):  = 161.62, 136.41, 135.85,
133.06, 132.54, 131.73, 129.59, 129.27, 128.94, 128.67, 128.49,
127.31, 126.42, 125.30, 124.98, 123.98, 123.80, 119.70.
1H NMR (400 MHz, CDCl3 + D2SO4):  = 7.45 (t, J = 7.5 Hz, 1 H), 7.31 (t,
J = 7.8 Hz, 2 H), 7.20 (d, J = 7.6 Hz, 2 H), 7.16–7.03 (m, 3 H), 7.01–6.85
(m, 6 H).
13C NMR (100 MHz, CDCl3 + D2SO4):  = 162.05, 146.90, 136.44,
135.39, 132.26, 130.08, 129.32, 128.86, 126.44, 126.33, 126.04,
124.92, 121.31, 120.28 (q, J = 256 Hz).
HRMS (ESI-TOF): m/z calcd for C20H16F3N2O [M + H]+: 357.1209;
found: 357.1217.
HRMS (ESI-TOF): m/z calcd for C23H1879BrN2 [M + H]+: 401.0648,
found: 401.0659.
6-Bromo-1,2-diphenyl-1H-benzo[d]imidazole (4)
N,N′-Diphenylbenzimidamide (3m)
Yield: 60 mg (57%); white solid; mp 154–155 °C.
Yield: 116 mg (85%); white solid; mp 143–144 °C.
1H NMR (400 MHz, acetone-d6):  = 8.45 (s, 1 H), 8.01 (s, 2 H), 7.34–
1H NMR (400 MHz, CDCl3):  = 7.88 (d, J = 7.6 Hz, 1 H), 7.66–7.59 (m, 2
H), 7.58–7.52 (m, 2 H), 7.42–7.16 (m, 8 H).
7.30 (m, 7 H), 7.06 (s, 3 H), 6.78–6.67 (m, 3 H).
13C NMR (100 MHz, CDCl3):  = 152.21, 142.99, 136.82, 136.01,
133.07, 129.60, 129.42, 128.89, 128.42, 123.53, 123.18, 122.33,
120.00, 110.15.
HRMS (ESI-TOF): m/z calcd for C19H1479BrN2 [M + H]+: 349.0335;
found: 349.0346.
13C NMR (100 MHz, acetone-d6):  = 154.68, 150.94, 141.61, 135.32,
128.93, 128.88, 128.31, 128.20, 128.00, 122.40, 122.04, 121.05,
119.47.
HRMS (ESI-TOF): m/z calcd for C19H17N2 [M + H]+: 273.1386; found:
273.1391.
4-(4-Bromophenyl)-2,3-diphenyl-1,2,4-oxadiazolidin-5-one (5a)
N-Phenyl-N′-(m-tolyl)benzimidamide (3n)
In a 10 mL round-bottomed flask, a mixture of 1a (98 mg, 0.5 mmol)
and 2a (108 mg, 0.5 mmol) in CH2Cl2 (2.0 mL) was stirred overnight at
rt until the substrate 1a was consumed as indicated by TLC (ca. 9 h).
The resulting mixture was concentrated in vacuo. Then, the residue
was washed with PE to afford 5a as a white solid; yield: 193 mg (98%);
mp 139–140 °C.
1H NMR (400 MHz, CDCl3):  = 7.50–7.47 (m, 2 H), 7.45–7.43 (m, 3 H),
7.41–7.36 (m, 4 H), 7.24–7.19 (m, 5 H), 6.11 (s, 1 H).
13C NMR (101 MHz, CDCl3):  = 154.0, 149.1, 135.2, 134.7, 132.2,
Yield: 126 mg (88%); white solid; mp 114–115 °C.
1H NMR (400 MHz, CDCl3 + D2SO4):  = 7.61–7.54 (m, 2 H), 7.54–7.41
(m, 5 H), 7.35–7.30 (m, 2 H), 7.30–7.23 (m, 2 H), 7.20 (t, J = 7.9 Hz, 1
H), 7.11–7.04 (m, 1 H), 6.99 (d, J = 7.5 Hz, 1 H), 6.20 (s, 1 H), 2.33 (s, 3
H).
13C NMR (100 MHz, CDCl3 + D2SO4):  = 154.32, 149.61, 139.37,
135.93, 135.58, 134.49, 130.01, 129.46, 129.27, 129.01, 127.15,
126.55, 125.71, 121.76, 118.07, 117.28, 86.54, 21.50.
130.2, 129.5, 129.4, 127.1, 125.9, 122.4, 118.8, 117.4, 86.3.
HRMS (APCI): m/z calcd for C20H1679BrN2O2 [M + H]+: 395.0390; found:
HRMS (ESI-TOF): m/z calcd for C20H19N2 [M + H]+: 287.1543; found:
287.1555.
395.0370.
N′-(4-Chlorophenyl)-N-phenylbenzimidamide (3o)
Yield: 132 mg (86%); white solid; mp 120–121 °C.
Funding Information
1H NMR (400 MHz, CDCl3 + D2SO4):  = 14.16 (br s, 1 H), 7.42 (t, J = 7.5
Hz, 1 H), 7.28 (t, J = 7.8 Hz, 2 H), 7.18 (d, J = 7.5 Hz, 2 H), 7.13–7.01 (m,
5 H), 6.90 (d, J = 6.8 Hz, 2 H), 6.83 (d, J = 8.7 Hz, 2 H).
13C NMR (100 MHz, CDCl3 + D2SO4):  = 162.02, 136.41, 135.32,
132.17, 131.83, 130.11, 129.27, 128.92, 128.83, 126.42, 126.32,
126.03, 124.95.
This work was financially supported by the talent plan of Jiangsu Nor-
mal University (16XLR013).
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Supporting Information
HRMS (ESI-TOF): m/z calcd for C19H1635ClN2 [M + H]+: 307.0997,
found: 307.1003.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1707989.
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N-Phenyl-N′-[4-(trifluoromethyl)phenyl]benzimidamide (3p)
Yield: 153 mg (90%); white solid; mp 110–111 °C.
References
1H NMR (400 MHz, CDCl3 + D2SO4):  = 7.52–7.45 (m, 1 H), 7.40–7.30
(m, 5 H), 7.24 (d, J = 7.6 Hz, 2 H), 7.18–7.09 (m, 3 H), 7.02 (d, J = 8.4 Hz,
2 H), 6.98–6.92 (m, 2 H).
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