Simultaneous Formation and Functionalization of Aryliminophosphoranes Using 1,3-Dihydro-1 H-benzimidazol-2-ones as Precursors

Article abstract of DOI:10.1021/acs.joc.0c01979

An atom- and step-economic synthesis of aryliminophosphoranes bearing ortho urea was achieved via unprecedented Ph3P-I2 mediated ring-opening of 1,3-dihydro-1H-benzimidazol-2-ones with secondary amines. Tandem aza-Wittig/heterocyclization of the functionalized aryliminophosphoranes upon treatment with isothiocyanates enables a facile access to a single regioisomer of N1-substituted 2-aminobenzimidazoles as well as fused tetracyclic quinazolinone derivatives in one-pot. 31P{1H} NMR studies suggested that the urea C-N bond of benzimidazolone is weakened by N-phosphorylation, leading to aminolysis rather than the expected deoxygenative amination.

Full text of DOI:10.1021/acs.joc.0c01979

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Note
Simultaneous Formation and Functionalization of
Aryliminophosphoranes Using 1,3-Dihydro‑1H‑benzimidazol-2-ones
as Precursors
Mookda Pattarawarapan, Dolnapa Yamano, Nittaya Wiriya, Saranphong Yimklan,
and Wong Phakhodee*
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ABSTRACT: An atom- and step-economic synthesis of arylimi-
nophosphoranes bearing ortho urea was achieved via unprece-
dented Ph3P-I2 mediated ring-opening of 1,3-dihydro-1H-benzimi-
dazol-2-ones with secondary amines. Tandem aza-Wittig/hetero-
cyclization of the functionalized aryliminophosphoranes upon
treatment with isothiocyanates enables a facile access to a single
regioisomer of N1-substituted 2-aminobenzimidazoles as well as
fused tetracyclic quinazolinone derivatives in one-pot. 31P{1H}
NMR studies suggested that the urea C−N bond of benzimida-
zolone is weakened by N-phosphorylation, leading to aminolysis
rather than the expected deoxygenative amination.
Scheme 1. Synthetic Approaches toward
Iminophosphoranes
ryliminophosphoranes are versatile reagents in CN
Abond formation which have found numerous applications
in the synthesis of diverse N-containing molecules.1 Their use
in an aza-Wittig type reaction offers practical approaches
toward a vast number of interesting derivatives with
pharmacological and biological significances.2 Moreover, a
highly polarized PN bond makes them valuable ligands for
catalysis applications.3
Owning to their synthetic potential, the synthesis and
application of iminophosphoranes have attracted considerable
attention among organic and medicinal chemists. Since it was
first introduced in 1919,4 the Staudinger reaction between
aromatic azides and phosphines has been the most commonly
used method for the preparation of aryliminophosphoranes
(Scheme 1a).1,5 Other alternative approaches include the
reaction of amines with phosphines in the presence of
halogenating agents,6 azodicarboxylates,7 or ethylenedicarbox-
ylates (Scheme 1b),8 the reaction of ylides with Schiff bases9 or
nitriles10 (Scheme 1c), alkylation of aminophosphanes
(Scheme 1d),11 condensation of N-aryl-2-nitrosoanilines12 or
2-nitrodiarylamines13 with triphenylphosphine (Scheme 1e), as
well as condensation of triphenylphosphine oxide with N-
monosubstituted arylureas (Scheme 1f).14 These methods
have their own merits; however, the preparation of complex
iminophosphorane structures often requires a tedious synthetic
and purification process involving multistep functionalization
which may hinder their practical utility toward challenging
targets.
activator,15 rather than the expected deoxygenative amination
toward 3 as has been observed in the POCl3-mediated
reaction,16 1,3-dihydro-1H-benzimidazol-2-ones 1 underwent
an unprecedented aminolysis at the cyclic urea C−N bond to
yield aryliminophosphoranes bearing an ortho urea moiety 2
Received: August 17, 2020
In our ongoing work involving phosphonium-mediated
synthesis of 2-aminoheterocycles using Ph3P-I2 as an
https://dx.doi.org/10.1021/acs.joc.0c01979
© XXXX American Chemical Society
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A

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Note
exclusively (Scheme 1). Although a similar ring-opening
reaction of the urethane derivatives has previously been
observed,15d this discovery is still rather surprising since the
urea bonds are extremely stable due to the conjugation
stabilization effects of its dual amide structure.17
Since ortho-functionalized aryliminophosphoranes would
enable a straightforward and step-economic construction of a
vast number of N-heterocyclic frameworks, while the bifunc-
tional derivatives are potentially useful in asymmetric
catalysis,3,18 this prompted us to explore the reaction in detail
in order to better understand the reaction mechanism and
factors governing their formation. Presented here is a novel
pathway toward a new type of aryliminophosphoranes. Their
application in aza-Wittig/heterocyclization furnishing N1-
substituted 2-aminobenzimidazoles as well as tetracyclic
quinazolinone derivatives is also demonstrated.
without detectable formation of the corresponding 2-amino-
benzimidazoles 3. Unfortunately, 1a failed to react with all the
tested primary amines (benzylamine, cyclohexylamine, and
aniline, data not shown). This could be attributed to a
competitive substitution reaction at the phosphorus center of
the formed phosphonium intermediate(s) by these nucleo-
philes. Indeed, cyclohexylaminophosphonium salt was isolated
(79% yield) from the reaction of 1a with cyclohexylamine.
The identities of all the products were consistent with the
NMR and MS data. In the case of compound 2c, the proposed
iminophosphorane structure was unambiguously confirmed by
X-ray crystallography. As illustrated in Figures S1 and S2
(Supporting Information (SI)), the N−P−C and C−P−C
bond angles within the range of 106.9−114.6° indicate the
distorted tetrahedral arrangement about the phosphorus and
are in the expected range. Noteworthy, the short P1−N3 bond
distance, 1.573 Å, suggests the double bond character (1.54 Å)
rather than a single bond (1.78 Å).19 An intramolecular
hydrogen bonding interaction of 2.115 Å also exists between
the N−H of the urea residue and N3 of the iminophosphorane
2c.
In our preliminary study, 1,3-dihydro-1H-benzimidazol-2-
one 1a was treated with a series of amines under our previously
reported conditions.15d According to Scheme 2, compound 1a
a
Scheme 2. Substrate Scope with Respect to Amines
Electronic and steric effects of the substrates on the yield
and regioselectivity of the reaction were next examined using
different substituted benzimidazol-2-one derivatives 1. As
summarized in Scheme 3, the electronic properties of the
Scheme 3. Substrate Scope with Respect to
a
Benzimidazolone Precursors
a
Reaction conditions: 1a (0.74 mmol), PPh3 (1.11 mmol), I2 (1.11
mmol), amine (0.89 mmol), Et3N (2.22 mmol), CH2Cl2 (5 mL).
b
Reaction performed in gram scale using 1a (10 mmol).
a
Reaction conditions: 1 (0.74 mmol), PPh3 (1.11 mmol), I2 (1.11
mmol), diethylamine (0.89 mmol), Et3N (2.22 mmol), CH2Cl2 (5
mL).
underwent ring-opening with secondary aliphatic amines both
acyclic and cyclic systems to furnish aryliminophosphoranes 2
at room temperature. Products 2a−2c were afforded in high
yields within a short reaction time when using dialkylamines
with different carbon chain lengths. The preparation of 2a is
also feasible under gram-scale synthesis (see parentheses).
Steric hindrance caused by the alkyl substituent of the amine
lowered the yield of the product 2d slightly. To our delight, the
reaction is still compatible with highly hindered diisopropyl-
amine, albeit with long reaction time and low yield of 2e due to
competing formation of pseudo-dimerized product 4. The
reaction of 1a also proceeded effectively with less hindered
cyclic amines, furnishing the products 2f−2h in high yields
substituents at the phenyl ring of 1 exert little influence on the
product yield and regioselectivity. While symmetrically
substituted substrates 1b and 1c gave rise to high yield of
the corresponding products 2i and 2j, the reaction of
unsymmetrical substrates generally provides an approximately
1:1 mixture of the inseparable regioisomers 2k−2n based on
the NMR analysis of the crude product mixture. Only for the
nitro containing substrate 1f, isomer 2m having the nitro group
para to the NP bond was isolated as a major product.
B
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Scheme 4. Aza-Wittig/Heterocyclization
By comparing the two benzimidazolone derivatives that
exhibit complementary substitution patterns, 1g and 1h, the
regioselectivity of the reaction was found to be highly sensitive
to steric factor. In contrast to the 1:1 mixture of the products
2n and 2n′ obtained from the reaction of 1g, the formation of
sterically less hindered product 2o was preferred with 1h
having an ortho methyl group.
Most of the iminophosphoranes 2 are stable compounds
which can be purified by column chromatography and stored
at room temperature without detectable decomposition. As a
representative, compound 2a remained unchanged even when
stirring in wet THF or in 1 M HCl in MeOH (16 h) as neither
hydrolysis nor reduction to the corresponding aryl amine was
observed.
the tested reactions, competitive formation of self-condensed
products 3 was not observed.
To gain insight into the mechanism for the formation of 2,
progress of the reaction between 1a and dibenzylamine
(NHBn2) was monitored using 31P{1H} NMR (see Figures
S3−S5 and discussion in SI). On the basis of the above results
and the NMR data, the mechanism of the reaction was
proposed as depicted in Scheme 5. Treatment of 1 with the
Scheme 5. Proposed Mechanism
To demonstrate the synthetic utility of 2, aza-Wittig/
heterocyclization toward fused N-heterocycles was examined in
the reaction with isothiocyanates 5 as shown in Scheme 4.
Under thermal conditions, the aza-Wittig reaction of 2 with the
isothiocyanate group initially provides carbodiimides.12 These
intermediates then undergo intramolecular cyclization with the
ortho urea NH to afford N1-substituted 2-aminobenzimidazoles
6 (method A).
The reaction proceeded smoothly with aryl isothiocyanates
containing an electron-withdrawing or electron-donating group
as well as alkyl isothiocyanate to provide 6a−6f in high yields.
The reaction also appears to be compatible with various
substituents on the aryl ring of 2, and even the presence of a
bulky ortho urea group can be tolerated (e.g., 6g−6j).
Remarkably, under method B, benzimidazole 6a along with
6k−6o could be prepared directly from 1a in good overall
yields through in situ formation of 2, followed by a sequential
aza-Wittig-cyclization reaction upon addition with phenyl
isothiocyanate. Furthermore, a single regioisomer of fused
tetracyclic quinazolinone derivatives 7 was readily afforded in
high yield through a one-pot reaction of 1a with amines and
methyl 2-isothiocyanatobenzoate. It is noteworthy that, in all
Ph3P-I2 mixture in the presence of base gives rise to
predominant formation of N-phosphorylated intermediate I
which could be in equilibrium with an aryloxyphosphonium
species II. Triggered by the presence of the N-phosphonium
group, I could undergo C−N bond cleavage upon attacking by
an amine, leading directly to aryliminophosphorane 2 (path a).
Although no other prominent signals were observed under the
31P{1H} NMR time scale, 2 could possibly be obtained
through an addition of an amine to an isocyanate III derived
from bond dissociation of I as observed in the reaction of
hindered urea bonds (path b).20
In conclusion, we have disclosed a novel unconventional
route toward ortho-functionalized aryliminophosphoranes
through phosphonium-mediated ring-opening of 1,3-dihydro-
1H-benzimidazol-2-ones with amines. This step- and atom-
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Note
31P{1H} NMR (202 MHz, CDCl3) δ 8.11; HRMS (ESI) m/z [M +
economic approach allows a convenient access to various
iminophosphoranes, which enables the direct one-pot
regioselective synthesis of N1-substituted 2-aminobenzimida-
zoles as well as fused tetracyclic quinazolinones via tandem
aza-Wittig/heterocyclization. With an increasing number of
potent N-heterocycles with endocyclic urea being discovered,21
it is anticipated that this protocol would open a new avenue
toward valuable structural motifs that are otherwise inacces-
sible or difficult to obtain with the existing methodologies.
Further studies based on this strategy are currently underway.
H]+ calcd for C33H39N3OP 524.2825, found 524.2829.
1,1-Dibenzyl-3-(2-((triphenyl-λ5-phosphanylidene)amino)-
phenyl)urea (Scheme 2, 2c). Pale yellow solid; (0.3942 g, 90% yield);
Rf 0.35 (30% EtOAc/hexanes); mp 190−192 °C; 1H NMR (500
MHz, CDCl3) δ 9.19 (s, 1H), 8.39 (d, J = 7.5 Hz, 1H), 7.55 (d, J =
8.0 Hz, 3H), 7.53 (d, J = 8.0 Hz, 3H), 7.46 (t, J = 8.0 Hz, 3H), 7.32−
7.29 (m, 6H), 7.25−7.20 (m, 10H), 6.70 (t, J = 7.5 Hz, 1H), 6.51 (t, J
= 7.5 Hz, 1H), 6.37 (d, J = 7.5 Hz, 1H), 4.52 (s, 4H); 13C{1H} NMR
3
(125 MHz, CDCl3) δ 155.7, 138.9, 137.7, 134.30, 134.14 (d, Jpc
=
=
=
20.0 Hz), 132.41, 132.34 (d, 2Jpc = 8.75 Hz), 131.87, 131.84 (d, 4Jpc
1
3
3.75 Hz), 130.8, 130.0 (d, Jpc = 98.75 Hz), 128.73, 128.63 (d, Jpc
3
12.50 Hz), 128.6, 127.7, 127.0, 120.9, 118.95, 118.88 (d, Jpc = 8.75
Hz), 118.1, 116.7, 49.2; 31P{1H} NMR (202 MHz, CDCl3) δ 8.55;
HRMS (ESI) m/z [M + H]+ calcd for C39H35N3OP 592.2512, found
592.2517.
EXPERIMENTAL SECTION
■
General Information. All reagents including 1,3-dihydro-1H-
benzimidazol-2-ones 1 (1a, 1b, 1f) were purchased from Sigma-
Aldrich or TCI and used without further purification. Compounds
1c,22a 1d,22b 1e,22c 1g,22d and 1h22e were synthesized according to the
reported procedures. All reactions were run in flame- or oven-dried
glassware under N2 gas. The reaction was monitored by thin-layer
chromatography carried out on silica gel plates (60F254, MERCK,
Germany) and visualized under UV light (254 nm). Column
chromatography was performed over silica gel 60 (70−230 mesh,
MERCK, Germany). Melting points were determined using Mettler
Toledo DSC equipment at a heating rate of 6 °C/min and are
uncorrected. NMR spectra were recorded using a Bruker AVANCE
1,1-Dicyclohexyl-3-(2-((triphenyl-λ5-phosphanylidene)amino)-
phenyl)urea (Scheme 2, 2d). Colorless oil (0.3112 g, 73% yield); Rf
0.39 (40% EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 8.39 (s,
1H), 8.10 (ddd, J = 8.0, 2.8, 1.5 Hz, 1H), 7.74−7.69 (m, 6H), 7.53
(td, J = 7.5, 1.5 Hz, 3H), 7.46−7.42 (m, 6H), 6.65 (td, J = 8.0, 1.5 Hz,
1H), 6.44 (td, J = 8.0, 1.5 Hz, 1H), 6.34 (dt, J = 8.0, 1.5 Hz, 1H),
3.41−3.35 (m, 2H), 1.83 (q, J = 12.5 Hz, 4H), 1.63 (t, J = 12.5 Hz,
8H), 1.46 (br d, J = 13.0 Hz, 2H), 1.19−1.09 (m, 4H), 0.98−0.89 (m,
2H); 13C{1H} NMR (125 MHz, CDCl3) δ 155.5, 138.9, 134.7, 134.5
(d, 3Jpc = 20.0 Hz), 132.7, 132.6 (d, 2Jpc = 10.0 Hz), 131.85, 131.82 (d,
4Jpc = 3.8 Hz), 131.1, 130.3 (d, 1Jpc = 98.8 Hz), 128.8, 128.7 (d, 3Jpc
=
1
(400 and 500 MHz for H). Chemical shifts were reported in parts
12.5 Hz), 120.2, 119.40, 119.32 (d, 3Jpc = 10.0 Hz), 118.0, 117.3, 55.7,
31.7, 26.4, 25.4; 31P{1H} NMR (202 MHz, CDCl3) δ 8.04; HRMS
(ESI) m/z [M + H]+ calcd for C37H43N3OP 576.3138, found
576.3135.
per million (ppm, δ) downfield from tetramethylsilane (TMS).
Splitting patterns are described as singlet (s), doublet (d), triplet (t),
quartet (q), quintet (qui), sextet (sex), septet (sep), multiplet (m),
broad (br), doublet of doublets (dd), triplet of doublets (td), and
doublet of doublet of doublets (ddd). High-resolution mass spectra
(HRMS) were recorded using time-of-flight (TOF) via the
atmospheric pressure chemical ionization (APCI) or electrospray
ionization (ESI).
1,1-Diisopropyl-3-(2-((triphenyl-λ5-phosphanylidene)amino)-
phenyl)urea (Scheme 2, 2e). Yellow oil; (0.1470 g, 40% yield); Rf
0.41 (40% EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 8.61 (s,
1H), 8.23 (d, J = 8.0 Hz, 1H), 7.70 (t, J = 7.5 Hz, 6H), 7.54 (t, J = 7.5
Hz, 3H), 7.44 (t, J = 7.5 Hz, 6H), 6.66 (t, J = 8.0 Hz, 1H), 6.46 (t, J =
8.0 Hz, 1H), 6.37 (d, J = 8.0 Hz, 1H), 3.94 (sep, J = 6.5 Hz, 2H), 1.23
(d, J = 6.5 Hz, 12H); 13C{1H} NMR (125 MHz, CDCl3) δ 154.8,
General Procedure for the Synthesis of 2. To a solution of
iodine (281 mg, 1.11 mmol) and triphenylphosphine (291 mg, 1.11
mmol) in freshly distilled dichloromethane (5 mL) was added amine
(0.89 mmol) at 0 °C under N2. After that, 1,3-dihydro-1H-
benzimidazol-2-ones 1 (0.74 mmol) and triethylamine (0.31 mL,
2.22 mmol) were sequentially added, followed by warming up to
room temperature with continuous stirring. After completion of the
reaction, the crude mixture was concentrated under reduced pressure
before purification by column chromatography (CC) using ethyl
acetate/hexanes as the eluent.
3
2
138.8, 134.92, 134.76, (d, Jpc = 20.25 Hz), 132.70, 132.63 (d, Jpc
=
=
4
1
9.1 Hz), 131.92, 131.90 (d, Jpc = 3.25 Hz), 130.93, 130.13 (d, Jpc
99.0 Hz), 128.75, 128.65 (d, 3Jpc = 11.9 Hz), 120.3, 119.23, 119.15 (d,
3Jpc = 10.0 Hz), 118.1, 116.9, 45.4, 21.3; 31P{1H} NMR (202 MHz,
CDCl3) δ 8.95; HRMS (ESI) m/z [M + H]+ calcd for C31H35N3OP
496.2512, found 496.2516.
1′H-[1,2′-Bibenzo[d]imidazol]-2(3H)-one (Scheme 2, 4). Gray
powder; (0.0504 g, 27% yield); Rf 0.35 (30% EtOAc/hexanes); mp >
300 °C (dec.); 1H NMR (500 MHz, DMSO-d6) 12.46 (s, 1H), 11.72
(s, 1H), 8.47−8.144(m, 1H), 7.76−7.58 (m, 2H), 7.26−7.18 (m,
5H); 13C{1H} NMR (125 MHz, DMSO-d6) δ 152.9, 144.5, 129.1,
127.5, 123.9, 121.15, 121.09, 114.0, 109.9.
1,1-Diethyl-3-(2-((triphenyl-λ5-phosphanylidene)amino)phenyl)-
urea (Scheme 2, 2a). Yellow oil; (0.3011 g, 87% yielda; 3.8337 g, 82%
yieldb); Rf 0.32 (30% EtOAc/hexanes); 1H NMR (500 MHz, CDCl3)
δ 8.82 (s, 1H), 8.27 (d, J = 7.5 Hz, 1H), 7.72 (d, J = 7.5 Hz, 3H), 7.70
(d, J = 7.5 Hz, 3H), 7.54 (t, J = 7.5 Hz, 3H), 7.46−7,44 (m, 6H), 6.67
(t, J = 7.5 Hz, 1H), 6.49 (t, J = 7.5 Hz, 1H), 6.40 (d, J = 7.5 Hz, 1H),
3.37 (q, J = 7.0 Hz, 4H), 1.12 (t, J = 7.0 Hz, 6H); 13C{1H} NMR
N-(2-((Triphenyl-λ5-phosphanylidene)amino)phenyl)pyrrolidine-
1-carboxamide (Scheme 2, 2f). Pale yellow solid; (0.2897 g, 84%
1
3
yield); Rf 0.28 (40% EtOAc/hexanes); mp 222−225 °C; H NMR
(125 MHz, CDCl3) δ 155.2, 138.7, 134.6, 134.5 (d, Jpc = 20.0 Hz),
2
4
(500 MHz, CDCl3 + CD3OD) δ 8.35 (d, J = 8.0 Hz, 1H), 7.70 (t, J =
7.5 Hz, 6H), 7.56 (br s, 3H), 7.70−7.66 (m, 6H), 7.53 (s, 1H), 6.90
(t, J = 8.0 Hz, 1H), 6.74 (t, J = 8.0 Hz, 1H), 6.64 (d, J = 8.0 Hz, 1H),
3.66 (br s, 4H), 2.14 (br s, 4H); 13C{1H} NMR (125 MHz, CDCl3 +
132.5, 132.4 (d, Jpc = 10.0 Hz), 132.03, 132.00 (d, Jpc = 3.75 Hz),
1
3
130.9, 130.1 (d, Jpc = 100.0 Hz), 128.81, 128.71 (d, Jpc = 12.5 Hz),
3
120.5, 119.01, 118.94 (d, Jpc = 8.75 Hz), 118.1, 116.5, 41.5, 14.0;
31P{1H} NMR (202 MHz, CDCl3) δ 8.56; HRMS (ESI) m/z [M +
3
H]+ calcd for C29H31N3OP 468.2199, found 468.2195.
CD3OD) δ 154.8, 138.5, 134.01, 133.86 (d, Jpc = 18.8 Hz), 132.45,
2
1
1,1-Dibutyl-3-(2-((triphenyl-λ5-phosphanylidene)amino)phenyl)-
urea (Scheme 2, 2b). Off-white solid; (0.3489 g, 90% yield); Rf 0.30
(20% EtOAc/hexanes); mp 120−122 °C; 1H NMR (500 MHz,
CDCl3) δ 8.74 (s, 1H), 8.26 (d, J = 7.5 Hz, 1H), 7.72 (d, J = 8.0 Hz,
3H), 7.70 (d, J = 8.0 Hz, 3H), 7.54 (t, J = 8.0 Hz, 3H), 7.47−7.43 (m,
6H), 6.66 (t, J = 7.5 Hz, 1H), 6.47 (t, J = 7.5 Hz, 1H), 6.37 (d, J = 7.5
Hz, 1H), 3.28 (t, J = 7.5 Hz, 4H), 1.52 (qui, J = 7.5 Hz, 4H), 1.18
(sex, J = 7.5 Hz, 4H), 0.79 (t, J = 7.5 Hz, 6H); 13C{1H} NMR (125
MHz, CDCl3) δ 155.3, 138.7, 134.6, 134.5 (d, 3Jpc = 20.0 Hz), 132.56,
132.38 (d, Jpc = 8.8 Hz), 132.1, 130.79, 129.99 (d, Jpc = 100.0 Hz),
3
128.76, 128.66 (d, Jpc = 12.5 Hz), 121.6, 121.0, 119.35, 119.28 (d,
3Jpc = 8.8 Hz), 118.2, 116.6, 109.42, 45.6, 25.5; 31P{1H} NMR (202
MHz, CDCl3) δ 8.75; HRMS (ESI) m/z [M + H]+ calcd for
C29H29N3OP 466.2043, found 466.2043.
N-(2-((Triphenyl-λ5-phosphanylidene)amino)phenyl)piperidine-
1-carboxamide (Scheme 2, 2g). Pale yellow solid; (0.3091 g, 87%
1
yield); Rf 0.28 (30% EtOAc/hexanes); mp 177−179 °C; H NMR
(500 MHz, CDCl3) δ 8.90 (s, 1H), 8.18 (d, J = 7.5 Hz, 1H), 7.72 (d, J
= 8.0 Hz, 3H), 7.70 (d, J = 8.0 Hz, 3H), 7.55 (t, J = 8.0 Hz, 4H),
7.47−7.43 (m, 6H), 6.68 (t, J = 7.5 Hz, 1H), 6.50 (t, J = 7.5 Hz, 1H),
6.40 (t, J = 7.5 Hz, 1H), 3.48 (t, J = 5.0 Hz, 4H), 1.61−1.56 (m, 6H);
2
4
132.48 (d, Jpc = 10.0 Hz), 131.94, 131.92 (d, Jpc = 2.5 Hz), 131.1,
130.3 (d, 1Jpc = 98.75 Hz), 128.77, 128.68 (d, 3Jpc = 11.25 Hz), 120.4,
119.04, 118.97 (d, 3Jpc = 8.75 Hz), 118.2, 116.7, 47.4, 30.8, 20.2, 14.0;
D
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Note
4
13C{1H} NMR (125 MHz, CDCl3) δ 155.2, 138.6, 134.4, 134.2 (d,
2Jpc = 10.0 Hz), 132.26, 132.24 (d, Jpc = 2.5 Hz), 132.17, 132.15 (d,
4Jpc = 2.5 Hz), 130.50, 129.70 (d, 1Jpc = 100.0 Hz), 130.27, 129.48 (d,
1Jpc = 98.75 Hz), 128.9, 128.88, 128.83 (d, 3Jpc = 6.25 Hz), 128.78 (d,
2
3Jpc = 20.0 Hz), 132.5, 132.4 (d, Jpc = 8.75 Hz), 131.99, 131.97 (d,
1
4Jpc = 2.5 Hz), 131.0, 130.2 (d, Jpc = 100.0 Hz), 128.78, 128.69 (d,
3
3Jpc = 11.25 Hz), 120.7, 118.91, 118.84 (d, Jpc = 8.75 Hz), 118.2,
3Jpc = 12.5 Hz), 123.0, 121.22, 121.14 (d, Jpc = 10.0 Hz), 120.6,
119.61, 119.54 (d, Jpc = 8.75 Hz), 119.2, 117.5, 112.9, 110.4, 41.53,
3
116.7, 45.1, 25.8, 24.7; 31P{1H} NMR (202 MHz, CDCl3) δ 7.73;
HRMS (ESI) m/z [M + H]+ calcd for C30H31N3OP 480.2199, found
480.2201.
3
41.46, 13.90; 31P{1H} NMR (202 MHz, CDCl3) δ 7.81, 7.62; HRMS
(ESI) m/z [M + H]+ calcd for C29H3079BrN3OP 546.1304, found
546.1307; calcd for C29H3081BrN3OP 548.1284, found 548.1288.
1,1-Diethyl-3-(5-iodo-2-((triphenyl-λ5-phosphaneylidene)-
amino)phenyl)urea and 1,1-Diethyl-3-(4-iodo-2-((triphenyl-λ5-
phosphaneylidene)amino)phenyl)urea (Scheme 3, 2l and 2l′).
Yellow oil; (0.3603 g, 82% yield, ratio 2l:2l′ 1.4:1); Rf 0.35 (30%
N-(2-((Triphenyl-λ5-phosphanylidene)amino)phenyl)-
morpholine-4-carboxamide (Scheme 2, 2h). White solid; (0.2711 g,
1
76% yield); Rf 0.30 (40% EtOAc/hexanes); mp 179−180 °C; H
NMR (500 MHz, CDCl3) δ 8.94 (s, 1H), 8.15 (d, J = 8.0 Hz, 1H),
7.71 (d, J = 7.5 Hz, 3H), 7.68 (d, J = 7.5 Hz, 3H), 7.55 (t, J = 7.5 Hz,
3H), 7.47−7.44 (m, 6H), 6.69 (t, J = 8.0 Hz, 1H), 6.53 (t, J = 8.0,
1H), 6.41 (d, J = 8.0 Hz, 1H), 3.68 (t, J = 5.0 Hz, 4H), 3.47 (t, J = 5.0
Hz, 4H); 13C{1H} NMR (125 MHz, CDCl3) δ 155.2, 138.8, 133.8,
1
EtOAc/hexanes); H NMR (500 MHz, CDCl3) δ 8.73 (s, 1H), 8.66
(s, 1H), 8.62 (t, J = 2.5 Hz, 1H), 8.02 (d, J = 8.5 Hz, 1H), 7.71−7.66
(m, 12H), 7.59−7.54 (m, 6H), 7.50−7.44 (m, 12H), 6.95 (d, J = 8.5
Hz, 1H), 6.76 (d, J = 8.0 Hz, 1H), 6.59 (s, 1H), 6.10 (d, J = 8.0 Hz,
1H), 3.35 (q, J = 7.2 Hz, 8H), 1.11 (t, J = 7.2 Hz, 12H); 13C{1H}
NMR (125 MHz, CDCl3) δ 154.7, 154.6, 140.8, 138.7, 136.09, 135.93
(d, 3Jpc = 20.0 Hz), 134.53, 134.37 (d, 2Jpc = 20.0 Hz), 132.49, 132.40,
(d, 2Jpc = 10.0 Hz), 132.47, 132.40 (d, 2Jpc = 8.75 Hz), 132.28, 132.25
(d, 4Jpc = 3.75 Hz), 132.21, 132.18 (d, 4Jpc = 3.75 Hz), 130.41,129.62
3
2
133.6 (d, Jpc = 20.0 Hz), 132.5, 132.1 (d, Jpc = 10.0 Hz), 132.13,
4
1
132.11 (d, Jpc = 2.5 Hz), 130.9, 130.1 (d, Jpc = 100.0 Hz), 128.82,
128.73 (d, 3Jpc = 11.25 Hz), 121.2, 118.95, 118.88 (d, 3Jpc = 8.75 Hz),
118.2, 116.8, 66.7, 44.1; 31P{1H} NMR (202 MHz, CDCl3) δ 8.52;
HRMS (ESI) m/z [M + H]+ calcd for C29H29N3O2P 482.1992, found
482.1994.
1
1
(Cyclohexylamino)triphenylphosphonium iodide. White solid;
(0.2849 g, 79% yield); Rf 0.34 (10% MeOH/EtOAc); mp 188−189
°C; 1H NMR (500 MHz, CDCl3) NMR δ 7.85−7.81 (m, 6H), 7.77−
7.73 (m, 3H), 7.65−7.61 (m, 6H), 6.89 (t, J = 10.1 Hz, 1H), 2.85−
2.76 (m, 1H), 2.10−2.02 (m, 2H), 1.70−1.66 (m, 4H), 1.47−1.43
(m, 1H), 1.19−1.12 (m, 1H), 0.99−0.89 (m, 2H); 13C{1H} NMR
(d, Jpc = 98.75 Hz), 130.24, 129.44 (d, Jpc = 100.0 Hz), 129.3,
128.93, 128.83 (d, 3Jpc = 12.5 Hz), 128.90, 128.80 (d, 3Jpc = 12.5 Hz),
3
127.11, 127.03 (d, Jpc = 10.0 Hz), 126.9, 124.7, 120.47, 120.39 (d,
3Jpc = 10.0 Hz), 118.2, 83.6, 80.1, 41.55, 41.48, 14.0; 31P{1H} NMR
(202 MHz, CDCl3) δ 9.89, 9.70; HRMS (ESI) m/z [M + H]+ calcd
for C29H30IN3OP 594.1166, found 594.1161.
4
1,1-Diethyl-3-(4-nitro-2-((triphenyl-λ5-phosphanylidene)amino)-
phenyl)urea (Scheme 3, 2m). Yellow oil; (0.2463 g, 65% yield); Rf
0.34 (40% EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 9.17 (s,
1H), 8.72 (s, 1H), 7.69 (t, J = 7.5 Hz, 6H), 7.62 (t, J = 7.5 Hz, 3H),
7.53−7.50 (m, 6H), 7.47 (dd, J = 9.0, 2.0 Hz, 1H), 6.25 (d, J = 9.0
Hz, 1H), 3.39 (q, J = 7.0 Hz, 4H), 1.15 (t, J = 7.0 Hz, 6H); 13C{1H}
NMR (125 MHz, CDCl3) δ 154.4, 147.0, 138.7, 134.10, 133.94 (d,
(125 MHz, CDCl3) δ 134.79, 134.77 (d, Jpc = 3.1 Hz), 133.87,
133.78 (d, 3Jpc = 11.2 Hz), 129.86, 129.76 (d, 2Jpc = 13.2 Hz), 122.24,
1
2
121.42 (d, Jpc = 103.0 Hz), 54.48, 54.46 (d, Jpc = 2.8 Hz), 35.23,
3
35.19 (d, Jpc = 4.4 Hz), 25.8, 24.6; 31P{1H} NMR (202 MHz,
CDCl3) δ 36.07; HRMS (ESI) m/z [M − I]+ calcd for C24H27N3P
360.1876, found 360.1873.
3-(4,5-Dichloro-2-((triphenyl-λ5-phosphanylidene)amino)-
phenyl)-1,1-diethylurea (Scheme 3, 2i). Yellow solid; (0.3255 g, 82%
4
3Jpc = 20.0 Hz), 132.76, 132.73 (d, Jpc = 3.8 Hz), 132.46, 132.38 (d,
1
yield); mp 170−172 °C; Rf 0.32 (30% EtOAc/hexanes); H NMR
3
2Jpc = 10.0 Hz), 129.19, 129.09 (d, Jpc = 12.5 Hz), 129.0, 128.2 (d,
(500 MHz, CDCl3) δ 8.66 (s, 1H), 8.42 (s, 1H), 7.69−7.66 (m, 6H),
7.58 (t, J = 7.5 Hz, 3H), 7.49 (t, J = 7.5 Hz, 6H), 6.32 (s, 1H), 3.35
(q, J = 7.0 Hz, 4H), 1.12 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (125
MHz, CDCl3) δ 154.4, 138.8, 134.3, 134.1 (d, 3Jpc = 20.0 Hz), 132.44,
132.36 (2Jpc = 9.9 Hz), 132.40, 132.38 (d, 4Jpc = 2.8 Hz), 129.9, 129.1
1Jpc = 100.0 Hz), 117.8, 116.95, 116.86 (d, 3Jpc = 11.3 Hz), 111.8, 41.6,
13.9; 31P{1H} NMR (202 MHz, CDCl3) δ 13.29; HRMS (ESI) m/z
[M + H]+ calcd for C29H30N4O3P 513.2050, found 513.2054.
1,1-Diethyl-3-(4-nitro-2-((triphenyl-λ5-phosphanylidene)amino)-
phenyl)urea (Scheme 3, 2m′). Yellow solid; (0.0831 g, 22% yield); Rf
1
3
(d, Jpc = 99.9 Hz), 129.0, 128.9 (d, Jpc = 11.25 Hz), 122.5, 120.5,
1
0.34 (40% EtOAc/hexanes); mp 158−160 °C; H NMR (500 MHz,
119.05, 118.97 (d, Jpc = 8.75 Hz), 117.4, 41.5, 13.9; 31P{1H} NMR
3
CDCl3) δ 9.18 (s, 1H), 8.36 (d, J = 8.0 Hz, 1H), 7.73 (t, J = 7.5 Hz,
6H), 7.61 (d, J = 7.5 Hz, 3H), 7.52−7.49 (m, 6H), 7.17 (s, 1H), 3.40
(q, J = 7.0 Hz, 4H), 1.15 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (125
(202 MHz, CDCl3) δ 10.49; HRMS (ESI) m/z [M + H]+ calcd for
C29H2935ClN3OP 536.1420, found 536.1419; calcd for
C29H2937ClN3OP 540.1360, found 540.1363.
3
MHz, CDCl3) δ 154.2, 141.16, 141.00 (d, Jpc = 20.0 Hz), 140.95,
3-(4,5-Dimethoxy-2-((triphenyl-λ5-phosphanylidene)amino)-
phenyl)-1,1-diethylurea (Scheme 3, 2j). Yellow oil; (0.3516 g, 90%
yield) ; Rf 0.30 (15% acetone/hexanes); 1H NMR (500 MHz, CDCl3)
δ 8.49 (s, 1H), 8.11 (s, 1H), 7.73−7.69 (m, 6H), 7.57−7.54 (m, 3H),
7.48−7.45 (m, 6H), 6.01 (s, 1H), 3.84 (s, 3H), 3.36 (d, J = 7.0 Hz,
4H), 3.30 (s, 3H), 1.13 (d, J = 7.0 Hz, 6H); 13C{1H} NMR (125
139.2, 132.58, 132.56 (d, 4Jpc = 2.5 Hz), 132.47, 132.40 (d, 2Jpc = 8.75
Hz), 129.4, 128.5 (d, 1Jpc = 100.0 Hz), 129.11, 129.02 (d, 3Jpc = 11.25
3
Hz), 115.1, 114.5, 112.33, 112.25 (d, Jpc = 10.0 Hz), 41.7, 13.9;
31P{1H} NMR (202 MHz, CDCl3) δ 13.29; HRMS (ESI) m/z [M +
H]+ calcd for C29H30N4O3P 513.2050, found 513.2054.
1,1-Diethyl-3-(5-methyl-2-((triphenyl-λ5-phosphaneylidene)-
amino)phenyl)urea and 1,1-Diethyl-3-(4-methyl-2-((triphenyl-λ5-
phosphaneylidene)amino)phenyl)urea (Scheme 3, 2n and 2n′).
Yellow oil; (0.3384 g, 95% yield, ratio 2n:2n′; 1:1); Rf 0.35 (40%
2
MHz, CDCl3) δ 154.9, 142.2, 141.2, 132.5, 132.4 (d, Jpc = 9.5 Hz),
4
1
132.0, 131.97 (d, Jpc = 2.8 Hz), 131.2, 130.4 (d, Jpc = 97.0 Hz),
128.78, 128.68 (d, 3Jpc = 11.9 Hz), 127.93, 127.77 (d, 3Jpc = 20.0 Hz),
3
105.38, 105.31 (d, Jpc = 8.9 Hz), 102.7, 56.1, 55.9, 41.4, 13.9;
1
31P{1H} NMR (202 MHz, CDCl3) δ 7.14; HRMS (ESI) m/z [M +
EtOAc/hexanes); H NMR (500 MHz, CDCl3) δ 8.78 (s, 1H), 8.68
(s, 1H), 8.16 (s, 1H), 8.13 (d, J = 8.0 Hz, 1H), 7.74−7.69 (m, 12H),
7.56−7.52 (m 6H), 7.47−7.43 (m, 12H), 6.49 (d, J = 8.0 Hz, 1H),
6.31 (d, J = 8.5 Hz, 1H), 6.29 (d, J = 8.5 Hz, 1H), 6.20 (s, 1H), 3.36
(qui, J = 6.8 Hz, 8H), 2.21 (s, 3H), 1.94 (s, 3H), 1.12 (q, J = 6.8 Hz,
12H); 13C{1H} NMR (125 MHz, CDCl3) δ 154.9, 154.9, 138.5,
H]+ calcd for C31H35N3O3P 528.2411, found 528.2409.
3-(5-Bromo-2-((triphenyl-λ5-phosphaneylidene)amino)phenyl)-
1, 1-diethylurea and 3-(4-Bromo-2-((triphenyl-λ5 -
phosphaneylidene)amino)phenyl)-1,1-diethylurea (Scheme 3, 2k
and 2k′). Yellow oil; (0.3479 g, 86% yield, ratio 2k:2k′ 1:1); Rf 0.37
(30% EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 8.75 (s, 1H),
8.66 (s, 1H), 8.50−8.43 (t, J = 2.5 Hz 1H), 8.14 (dd, J = 8.5, 2.5 Hz,
1H), 7.71−7.66 (m, 12H), 7.59−7.54 (m, 6H), 7.50−7.44 (m, 12H),
6.76 (dd, J = 8.5, 2.0 Hz, 1H), 6.57 (dd, J = 8.5, 2.5 Hz, 1H), 6.42 (d,
J = 2.0 Hz, 1H), 6.20 (d, J = 8.5 Hz, 1H), 3.37−3.33 (m, 8H), 1.13−
1.10 (m, 12H); 13C{1H} NMR (125 MHz, CDCl3) δ 154.7, 154.6,
136.0, 134.3, 134.2 (d, 3Jpc = 20.0 Hz), 132.56, 132.49 (d, Jpc = 8.75
2
2
4
Hz), 132.54, 132.46 (d, Jpc = 10.0 Hz), 131.97, 131.95 (d, Jpc = 2.5
4
1
Hz), 131.92 (d, Jpc1= 3.75 Hz), 131.10, 130.30 (d, Jpc = 100.0 Hz),
3
131.08, 130.28 (d, Jpc = 100.0 Hz), 129.5, 128.77, 128.67 (d, Jpc
=
3
12.50 Hz), 127.4, 120.8, 120.02, 119.94 (d, Jpc = 10.0 Hz), 118.60,
118.52 (d, 3Jpc = 10.0 Hz), 118.58, 117.4, 116.3, 41.5, 41.4, 21.3, 21.0,
14.0; 31P{1H} NMR (202 MHz, CDCl3) δ 7.81, 7.62; HRMS (ESI)
m/z [M + H]+ calcd for C30H33N3OP 482.2356, found 482.2351.
3
140.5, 137.8, 135.76, 135.60 (d, Jpc = 20.0 Hz), 133.79, 133.63 (d,
2Jpc = 20.0 Hz), 132.49, 132.41 (d, 2Jpc = 10.0 Hz), 132.47, 132.39 (d,
E
https://dx.doi.org/10.1021/acs.joc.0c01979
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
1,1-Diethyl-3-(2-methyl-6-((triphenyl-λ5-phosphanylidene)-
amino)phenyl)urea (Scheme 3, 2o). Yellow oil; (0.3274 g, 92%
yield); Rf 0.28 (10% acetone/CH2Cl2); 1H NMR (500 MHz, CDCl3)
δ 7.73−7.69 (m, 6H), 7.53−7.50 (m, 3H), 7.44−7.41 (m, 6H), 7.33
(s, 1H), 6.58−6.54 (m, 2H), 6.27−6.25 (m, 1H), 3.40 (q, J = 7.0 Hz,
4H), 2.26 (s, 3H), 1.15 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (125
8.0 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 3.65 (sex, J = 7.0 Hz, 2H), 3.48
(sex, J = 7.0 Hz, 2H), 1.28 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (125
MHz, CDCl3) δ 153.3, 148.1, 144.8, 142.1, 141.2, 130.0, 125.4, 123.9,
122.4, 118.6, 117.6, 110.6, 42.9, 13.6; HRMS (ESI) m/z [M + H]+
calcd for C18H2035ClN4O 343.1320, found 343.1317, calcd for
C18H2037ClN4O 345.1290, found 345.1289.
2
MHz, CDCl3) δ 156.5, 143.4, 133.14, 132.68, 132.61 (d, Jpc = 9.8
N,N-Diethyl-2-((4-methoxyphenyl)amino)-1H-benzo[d]-
3
4
Hz), 132.61, 132.55 (d, Jpc = 7.5 Hz), 131.79, 131.77 (d, Jpc = 2.8
imidazole-1-carboxamide (Scheme 4, 6d). Yellow oil (0.1119 g,
1
3
1
Hz), 131.29, 130.49 (d, Jpc = 100.0 Hz), 128.67, 128.58 (d, Jpc
=
87% yield); Rf 0.36 (20% EtOAc/hexanes); H NMR (500 MHz,
3
11.9 Hz), 123.6, 120.3, 117.58, 117.50 (d, Jpc = 9.6 Hz), 41.5, 19.5,
14.0; 31P{1H} NMR (202 MHz, CDCl3) δ 5.53; HRMS (ESI) m/z
[M + H]+ calcd for C30H33N3OP 482.2356, found 482.2357.
Scale-Up for the Synthesis of 2a. To a mixture of iodine
(3.8075 g, 15 mmol) and triphenylphosphine (3.9049 g, 15 mmol) in
freshly distilled dichloromethane (50 mL) was added diethylamine
(1.25 mL, 12 mmol) at 0 °C under N2. After that, 1a (1.3415 g, 10
mmol) and triethylamine (4.20 mL, 30 mmol) were sequentially
added, followed by warming up to room temperature with continuous
stirring for 16 h. Then, the reaction mixture was quenched with water
and extracted with ethyl acetate (2 × 20 mL). The combined organic
phases were dried over anhydrous Na2SO4, and the solvent was
evaporated under reduced pressure. The crude product was purified
by flash column chromatography on silica gel, and the product 2a was
obtained as a yellow oil (3.8337 g, 82% yield).
CDCl3) δ 7.87 (s, 1H), 7.58 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 8.0 Hz,
1H), 7.19 (t, J = 8.0 Hz, 1H), 7.13−7.07 (m, 2H), 6.92 (d, J = 8.0 Hz,
2H), 3.80 (s, 3H), 3.58 (sex, J = 7.0 Hz, 2H), 3.44 (sex, J = 7.0 Hz,
2H), 1.23 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ
155.6, 153.6, 150.7, 142.1, 132.2, 130.4, 123.3, 121.0, 120.9, 117.8,
114.5, 110.1, 55.6, 42.8, 13.6; HRMS (ESI) m/z [M + H]+ calcd for
C19H23N4O2 339.1816, found 339.1816.
N,N-Diethyl-2-(o-tolylamino)-1H-benzo[d]imidazole-1-carboxa-
mide (Scheme 4, 6e). Red oil; (0.0859 g, 70% yield); Rf 0.32 (20%
EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 8.31 (d, J = 8.0 Hz,
1H), 8.14 (s, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H),
7.25−7.22 (m, 2H), 7.16−7.15 (m, 2H), 7.04 (t, J = 8.0 Hz, 1H),
3.62 (sex, J = 7.5 Hz, 2H), 3.50 (sex, J = 7.0 Hz, 2H), 2.38 (s, 3H),
1.28 (t, J = 7.5 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 153.9,
150.3, 142.0, 137.3, 130.4, 130.3, 127.1, 126.6, 123.4, 123.0, 121.2,
119.7, 118.0, 110.2, 43.0, 17.7, 13.7; HRMS (ESI) m/z [M + H]+
calcd for C19H23N4O 323.1866, found 323.1863.
2-(Benzylamino)-N,N-diethyl-1H-benzo[d]imidazole-1-carboxa-
mide (Scheme 4, 6f). Yellow oil (0.0944 g, 77% yield); Rf 0.26 (20%
EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 7.47 (d, J = 7.5 Hz,
1H), 7.40 (d, J = 7.5 Hz, 2H), 7.34 (t, J = 7.5 Hz, 2H), 7.28 (t, J = 7.5
Hz, 1H), 7.17 (t, J = 7.5 Hz, 1H), 7.08−7.02 (m, 2H), 5.96 (t, J = 5.5
Hz 1H), 4.73 (d, J = 5.5 Hz, 2H), 3.53 (sex, J = 7.0 Hz, 2H), 3.40
(sex, J = 7.0 Hz, 2H), 1.20 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (125
MHz, CDCl3) δ 154.3, 153.4, 142.3, 138.3, 131.3, 128.7, 127.7, 127.5,
123.2, 120.5, 117.1, 109.9, 47.1, 42.7, 13.7; HRMS (ESI) m/z [M +
H]+ calcd for C19H23N4O 323.1866, found 323.1868.
Synthesis of N1-Substituted 2-Aminobenzimidazoles 6
from 2 (Method A). In a 10 mL pressure tube, iminophosphorane
2 (0.38 mmol) was added with 1,2-dichloroethane (5 mL), followed
by isothiocyanate 5 (0.45 mmol) and triethylamine (0.16 mL, 1.14
mmol). The tightly capped vessel was then subjected to heating in a
preset oil bath at 120 °C until reaction completion. After cooling
down, the mixture was concentrated under reduced pressure before
column chromatography using ethyl acetate/hexanes as the eluent to
afford the product 6.
Synthesis of 6 or 7 from 1a (Method B). To a solution of
iodine (144 mg, 0.57 mmol) and triphenylphosphine (150 mg, 0.57
mmol) in freshly distilled dichloromethane (2 mL), amine (0.45
mmol), 2-hydroxybenzimidazole 1a (0.0510 g, 0.38 mmol), and
triethylamine (0.16 mL, 1.14 mmol) were sequentially added at 0 °C
under N2. After stirring at 25 °C for 1 h, the mixture was transferred
into a pressure tube before concentrated, followed by adding 1,2-
dichloroethane (5 mL) and isothiocyanate 5 or methyl 2-
isothiocyanatobenzoate (0.45 mmol). The tightly capped vessel was
heated in a preset oil bath at 120 °C until reaction completion. After
cooling down, the crude mixture was concentrated under reduced
pressure before purified by CC.
5,6-Dichloro-N,N-diethyl-2-(phenylamino)-1H-benzo[d]-
imidazole-1-carboxamide (Scheme 4, 6g). White solid; (0.1176 g,
1
82% yield); mp 115−116 °C; Rf 0.38 (20% EtOAc/hexanes); H
NMR (500 MHz, CDCl3) δ 8.07 (s, 1H), 7.65 (t, J = 8.0 Hz, 1H),
7.61 (s, 1H), 7.37 (t, J = 8.0 Hz, 1H), 7.15 (s, 1H), 7.08 (t, J = 8.0 Hz,
1H), 3.60−3.53 (m, 2H), 3.45−3.38 (m, 2H), 1.25 (t, J = 7.0 Hz,
6H); 13C{1H} NMR (125 MHz, CDCl3) δ 152.9, 151.0, 141.8, 138.3,
129.6, 129.2, 127.2, 124.6, 123.2, 119.1, 118.9, 111.5, 43.0, 13.6;
HRMS (ESI) m/z [M + H]+ calcd for C18H1935Cl2N4O 377.0930,
found 377.0926, calcd for C18H1937Cl2N4O 381.0870, found
381.0866.
N,N-Diethyl-2-(phenylamino)-1H-benzo[d]imidazole-1-carboxa-
mide (Scheme 4, 6a). Coloress oil (0.1045 g, 89% yield (A); 0.0889g,
1
76% yield (B); Rf 0.48 (40% EtOAc/hexanes); H NMR (500 MHz,
N,N-Diethyl-5,6-dimethoxy-2-(phenylamino)-1H-benzo[d]-
imidazole-1-carboxamide (Scheme 4, 6h). Green oil; (0.1194 g,
CDCl3) δ 8.11 (s, 1H), 7.73 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 7.5 Hz,
1H), 7.40 (t, J = 8.0 Hz, 2H), 7.25 (t, J = 7.5 Hz, 1H), 7.19−7.12 (m,
2H), 7.08 (t, J = 7.5 Hz, 1H), 3.62 (sex, J = 7.0 Hz, 2H), 3.48 (sex, J =
7.0 Hz, 2H), 1.27 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (125 MHz,
CDCl3) δ 153.6, 149.8, 142.0, 139.0, 130.2, 129.2, 123.4, 122.6, 121.3,
118.7, 118.0, 110.2, 42.8, 13.7; HRMS (ESI) m/z [M + H]+ calcd for
C18H21N4O 309.1710, found 309.1714.
N,N-Diethyl-2-((4-nitrophenyl)amino)-1H-benzo[d]imidazole-1-
carboxamide (Scheme 4, 6b). Yellow solid (0.1207 g, 90% yield);
mp 188−189 °C; Rf 0.37 (30% EtOAc/hexanes); 1H NMR (500
MHz, CDCl3) δ 8.67 (s, 1H), 8.27 (d, J = 9.0 Hz, 2H), 7.90 (d, J =
9.0 Hz, 2H), 7.65 (d, J = 8.0 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 7.24
(t, J = 8.0 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 3.65 (sex, J = 7.0 Hz,
2H), 3.48 (sex, J = 7.0 Hz, 2H), 1.28 (t, J = 7.0 Hz, 6H); 13C{1H}
NMR (125 MHz, CDCl3) δ 153.3, 148.1, 144.8, 142.1, 141.2, 130.0,
125.4, 123.9, 122.4, 118.6, 117.7, 110.6, 42.9, 13.6; HRMS (ESI) m/z
[M + H]+ calcd for C18H20N5O3 354.1561, found 354.1558.
1
85% yield); Rf 0.30 (60% EtOAc/hexanes); H NMR (500 MHz,
CDCl3) δ 8.01 (s, 1H), 7.65 (dd, J = 7.5, 1.0 Hz, 2H), 7.35 (t, J = 7.5
Hz, 2H), 7.16 (s, 1H), 7.03 (t, J = 7.5 Hz, 1H), 6.72 (s, 1H), 3.92 (s,
3H), 3.89 (s, 3H), 3.57 (sex, J = 7.0 Hz, 2H), 3.47 (sex, J = 7.5 Hz,
2H), 1.24 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ
153.7, 148.9, 147.0, 145.3, 139.1, 135.4, 129.1, 123.2, 122.3, 118.3,
101.7, 95.9, 56.9, 56.3, 42.6, 13.6; HRMS (ESI) m/z [M + H]+ calcd
for C20H25N4O3 369.1921, found 369.1915.
N,N-Diethyl-6-nitro-2-(phenylamino)-1H-benzo[d]imidazole-1-
carboxamide (Scheme 4, 6i). Yellow oil; (0.0629 g, 47% yield); Rf
0.37 (30% EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 8.41 (d,
J = 2.5 Hz, 1H), 8.09 (dd, J = 8.5, 2.5 Hz, 1H), 8.02 (br s, 1H), 7.69
(d, J = 8.0 Hz, 2H), 7.40 (t, J = 8.0 Hz, 2H), 7.15 (d, J = 8.0 Hz, 1H),
7.12 (t J = 8.5 Hz, 1H), 3.64−3.57 (m, 2H), 3.46−3.39 (m, 2H), 1.27
(t, J = 7.0 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 152.4,
151.8, 144.5, 142.2, 138.1, 134.8, 129.3, 123.6, 119.1, 117.4, 113.7,
109.4, 43.1, 13.6; HRMS (ESI) m/z [M + Na]+ calcd for
C18H19N5NaO3 376.1380, found 376.1379.
N,N-Diethyl-2-((4-chlorophenyl)amino)-1H-benzo[d]imidazole-
1-carboxamide (Scheme 4, 6c). White solid (0.1170 g, 90% yield);
mp 103−105 °C; Rf 0.25 (20% EtOAc/hexanes); 1H NMR (500
MHz, CDCl3) δ 8.67 (s, 1H), 8.27 (t, J = 9.0 Hz, 2H), 7.90 (d, J = 9.0
Hz, 2H), 7.65 (d, J = 8.0 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 7.24 (t, J =
N,N-Diisopropyl-2-(phenylamino)-1H-benzo[d]imidazole-1-car-
boxamide (Scheme 4, 6j). Colorless oil; (0.1127 g, 88% yield); Rf
0.46 (20% EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 7.65 (d,
F
https://dx.doi.org/10.1021/acs.joc.0c01979
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
J = 7.5 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.37 (t, J = 7.5 Hz, 1H),
7.20 (t, J = 8.0 Hz, 1H), 7.15−7.11 (m, 2H), 7.05 (t, J = 7.5 Hz, 1H),
3.81 (sep, J = 6.5 Hz, 1H), 1.48 (d, J = 6.5 Hz, 3H), 1.34 (d, J = 6.5
Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 151.4, 149.5, 141.7,
139.1, 130.9, 129.2, 123.1, 122.6, 121.2, 118.8, 118.0, 109.2, 49.3,
21.6, 20.9; HRMS (ESI) m/z [M + H]+ calcd for C20H25N4O
337.2023, found 337.2024.
1H), 7.74 (t, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.46−7.35 (m,
4H), 3.93−3.34 (m, 4H), 1.81 (br s, 2H), 1.61 (br s, 4H), 1.26−1.13
(m, 2H), 1.06 (br s, 3H), 0.73 (br s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 159.7, 150.2, 148.6, 144.3, 134.5, 130.2, 127.0, 126.7, 126.5,
126.3, 124.0, 123.5, 117.6, 116.3, 111.3, 49.1, 47.0, 30.7, 29.5, 20.0,
19.8, 13.9, 13.6; HRMS (ESI) m/z [M + H]+ calcd for C23H27N4O2
391.2129, found 391.2133.
N,N-Dibenzyl-12-oxobenzo[4,5]imidazo[2,1-b]quinazoline-6-
N,N-Dibutyl-2-(phenylamino)-1H-benzo[d]imidazole-1-carboxa-
mide (Scheme 4, 6k). White solid; (0.0992 g, 72% yield); mp 105−
106 °C; Rf 0.25 (5% EtOAc/hexanes); 1H NMR (500 MHz, CDCl3)
δ 8.09 (s, 1H), 7.68 (d, J = 7.5 Hz, 2H), 7.57 (d, J = 7.5 Hz, 1H), 7.36
(d, J = 7.5 Hz, 2H), 7.21 (t, J = 7.5 Hz, 1H), 7.14 (t, J = 7.5 Hz, 1H),
7.09−7.04 (m, 2H), 3.62−3.56 (m, 2H), 3.34−3.29 (m, 2H), 1.65−
1.57 (m, 4H), 1.35−1.26 (m, 4H), 0.86 (d, J = 7.0 Hz, 6H); 13C{1H}
NMR (125 MHz, CDCl3) δ 154.0, 149.9, 141.9, 139.0, 130.2, 129.2,
123.3, 122.6, 121.3, 118.8, 118.1, 110.3, 48.0, 30.1, 19.9, 13.6; HRMS
(ESI) m/z [M + H]+ calcd for C22H29N4O 365.2336, found 365.2336.
N,N-Dibenzyl-2-(phenylamino)-1H-benzo[d]imidazole-1-carbox-
amide (Scheme 4, 6l). Red oil; (0.1263 g, 77% yield); Rf 0.30 (10%
(12H)-carboxamide (Scheme 4, 7c). White solid; (0.1235 g, 71%
1
yield). mp 143−144 °C; Rf 0.43 (20% EtOAc/hexanes); H NMR
(500 MHz, CDCl3) δ 8.04 (d, J = 8.0 Hz, 1H), 7.73 (t, J = 8.0 Hz,
1H), 7.70 (d, J = 7.5 Hz, 1H) 7.62 (t, J = 8.0 Hz, 1H), 7.51 (t, J = 7.5
Hz, 1H), 7.44 (t, J = 8.0 Hz, 2H), 7.35−7.25 (m, 10H), 7.15 (t, J =
7.5 Hz, 1H), 4.72 (s, 4H); 13C{1H} NMR (125 MHz, CDCl3) δ
159.9, 154.5, 151.0, 136.8, 136.4, 133.3, 132.6, 132.34, 132.26, 131.59,
131.57, 128.80, 128.76, 128.6, 128.5, 128.04, 127.79, 124., 123.4,
112.6, 49.3; HRMS (ESI) m/z [M + H]+ calcd for C29H23N4O2
459.1816, found 459.18.17.
6-(Pyrrolidine-1-carbonyl)benzo[4,5]imidazo[2,1-b]quinazolin-
1
12(6H)-one (Scheme 4, 7d). White solid; (0.1013 g, 80% yield). mp
EtOAc/hexanes); H NMR (500 MHz, CDCl3) δ 8.23 (s, 1H), 7.67
1
148−149 °C; Rf 0.43 (20% EtOAc/hexanes); H NMR (500 MHz,
(d, J = 7.5 Hz, 2H), 7.55 (d, J = 8.0 Hz, 1H), 7.40−7.31 (m, 9H),
7.23−7.17 (m, 4H), 7.11−7.06 (m, 3H), 4.68 (d, J = 12.0 Hz, 2H),
4.36 (d, J = 15.0 Hz, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ
154.7, 150.0, 142.1, 138.9, 135.5, 130.3, 129.2, 129.1, 128.4, 128.2,
123.7, 122.8, 121.6, 119.1, 118.2, 110.4, 51.4; HRMS (ESI) m/z [M +
H]+ calcd for C28H25N4O 433.2023, found 433.2028.
(2-(Phenylamino)-1H-benzo[d]imidazol-1-yl)(pyrrolidin-1-yl)-
methanone (Scheme 4, 6m). Brown oil; (0.1013 g, 87% yield); Rf
0.19 (20% EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 8.39 (s,
1H), 7.74 (d, J = 7.5 Hz, 2H), 7.59 (d, J = 7.5 Hz, 1H), 7.39 (t, J = 7.5
Hz, 2H), 7.23 (t, J = 7.5 Hz, 1H), 7.16 (t, J = 7.5 Hz, 1H), 7.12 (d, J =
7.5 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 3.60 (br s, 4H), 2.00 (br s, 4H);
13C{1H} NMR (125 MHz, CDCl3) δ 152.7, 149.3, 142.1, 138.9,
129.6, 129.2, 123.2, 122.5, 121.1, 118.5, 118.0, 111.1, 48.7, 25.4;
HRMS (ESI) m/z [M + H]+ calcd for C18H19N4O 307.1553, found
307.1548.
(2-(Phenylamino)-1H-benzo[d]imidazol-1-yl)(piperidin-1-yl)-
methanone (Scheme 4, 6n). Red oil; (0.1019 g, 84% yield); Rf 0.35
(20% EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 8.43 (s, 1H),
7.75 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 8.0 Hz, 1H), 7.40 (t, J = 8.0 Hz,
2H), 7.24 (t, J = 8.0 Hz, 1H), 7.20−7.14 (m, 2H), 7.08 (t, J = 8.0 Hz,
1H), 3.69−3.65 (m, 2H), 3.46−3.41 (m, 2H), 1.76−1.69 (m, 6H);
13C{1H} NMR (125 MHz, CDCl3) δ 153.9, 150.3, 142.0, 137.3,
CDCl3) δ 8.63 (d, J = 8.0 Hz, 1H), 8.42 (d, J = 8.0 Hz, 1H), 7.75 (t, J
= 8.0 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H),
7.46−7.36 (m, 3H), 3.85 (t, J = 6.5 Hz, 2H), 3.71 (br s, 2H), 2.11 (t,
J = 6.5 Hz, 2H), 1.99 (t, J = 6.5 Hz, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 159.7, 148.4, 148.3, 143.8, 134.6, 129.6, 127.0, 126.5, 126.4,
126.2, 124.1, 123.6, 117.6, 116.2, 112.0, 48.4, 47.8, 25.9, 24.7; HRMS
(ESI) m/z [M + H]+ calcd for C19H17N4O2 333.1346, found
333.1342.
6-(Piperidine-1-carbonyl)benzo[4,5]imidazo[2,1-b]quinazolin-
12(6H)-one (Scheme 4, 7e). White solid; (0.1027 g, 78% yield); mp
1
236−237 °C; Rf 0.43 (20% EtOAc/hexanes); H NMR (500 MHz,
CDCl3) δ 8.61 (d, J = 8.0 Hz, 1H), 8.39 (d, J = 8.0 Hz, 1H), 7.74 (t, J
= 8.0 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.44
(t, J = 8.0 Hz, 1H), 7.40−7.35 (m, 2H), 3.85 (br s, 2H), 3.61 (br s,
1H), 3.41 (br s, 1H), 1.90 (br s, 2H), 1.75 (br s, 3H), 1.56 (br s, 1H);
13C{1H} NMR (125 MHz, CDCl3) δ 159.6, 149.0, 148.5, 144.2,
134.5, 130.1, 127.0, 126.6, 126.4, 126.2, 124.1, 123.6, 117.6, 116.2,
111.8, 48.9, 45.8, 26.3, 25.6, 24.2; HRMS (ESI) m/z [M + H]+ calcd
for C20H19N4O2 347.1503, found 347.1508.
6-(Morpholine-4-carbonyl)benzo[4,5]imidazo[2,1-b]-
quinazoline-6(12H)-carboxamide (Scheme 4, 7f). White solid;
(0.0889 g, 67% yield); mp 146−147 °C; Rf 0.41 (20% EtOAc/
1
hexanes); H NMR (500 MHz, CDCl3) δ 8.59 (d, J = 8.0 Hz, 1H),
130.4, 130.3, 127.1, 126.6, 123.4, 123.0, 121.2, 119.7, 118.0, 110.2,
43.0, 17.7, 13.7; HRMS (ESI) m/z [M + H]+ calcd for C19H21N4O
321.1710, found 321.1712.
8.37 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.0 Hz,
1H), 7.54 (d, J = 8.0 Hz, 1H), 7.45−7.35 (m, 3H), 4.12−3.70 (m,
8H); 13C{1H} NMR (125 MHz, CDCl3) δ 159.5, 149.4, 148.1, 144.0,
134.7, 129.9, 127.0, 126.7, 126.5, 126.1, 124.4, 123.9, 117.7, 116.2,
112.3, 66.7, 48.3, 45.1; HRMS (ESI) m/z [M + H]+ calcd for
C19H17N4O3 349.1295, found 349.1297.
Morpholino(2-(phenylamino)-1H-benzo[d]imidazol-1-yl)-
methanone (Scheme 3, 6o). Yellow oil; (0.0871 g, 71% yield); Rf
0.23 (20% EtOAc/hexanes); 1H NMR (500 MHz, CDCl3) δ 8.42 (s,
1H), 7.71 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.0 Hz, 1H), 7.37 (t, J = 8.0
Hz, 2H), 7.23 (t, J = 7.5 Hz, 1H), 7.18−7.12 (m, 2H), 7.06 (t, J = 7.5
Hz, 1H), 3.85−3.80 (m, 2H), 3.77−3.72 (m, 2H), 3.64−3.55 (m,
4H); 13C{1H} NMR (125 MHz, CDCl3) δ 153.8, 149.8, 142.0, 138.7,
129.7, 129.2, 123.9, 122.8, 121.5, 118.7, 118.2, 110.6, 66.6, 47.3;
HRMS (ESI) m/z [M + H]+ calcd for C18H19N4O2 323.1503, found
323.1502.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c01979.
■
sı
Copies of 1H NMR, 13C{1H} NMR spectra of all
products and 31P{1H} NMR spectra of selected
products, X-ray data of 2c, and 31P{1H} NMR reaction
monitoring studies (PDF)
N,N-Diethyl-12-oxobenzo[4,5]imidazo[2,1-b]quinazoline-6-
(12H)-carboxamide (Scheme 4, 7a). White solid; (0.0954 g, 75%
1
yield); mp 162−164 °C; Rf 0.44 (20% EtOAc/hexanes); H NMR
(500 MHz, CDCl3) δ 8.62 (d, J = 7.5 Hz, 1H), 8.40 (d, J = 7.5 Hz,
1H), 7.73 (t, J = 7.5 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.44 (t, J = 7.5
Hz, 1H), 7.43−7.35 (m, 3H), 3.73 (br s, 2H), 3.51 (br s, 2H), 1.43
(br s, 3H), 1.25 (br s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
159.7, 149.6, 148.6, 144.4, 134.5, 130.2, 126.9, 126.6, 126.4, 126.3,
124.0, 123.5, 117.6, 116.3, 111.0, 43.8, 42.2, 14.4, 12.9; HRMS (ESI)
m/z [M + H]+ calcd for C19H19N4O2 335.1503, found 335.1505.
N,N-Dibutyl-12-oxobenzo[4,5]imidazo[2,1-b]quinazoline-6-
(12H)-carboxamide (Scheme 4, 7b). White solid; (0.0863 g, 58%
Structure with X-ray data of 2c (CIF)
AUTHOR INFORMATION
Corresponding Author
■
Wong Phakhodee − Department of Chemistry, Faculty of
Science and Research Center on Chemistry for Development of
Health Promoting Products from Northern Resources, Faculty of
Science, Chiang Mai University, Chiang Mai 50200, Thailand;
1
yield); mp 107−108 °C; Rf 0.45 (20% EtOAc/hexanes); H NMR
(500 MHz, CDCl3) δ 8.62 (d, J = 7.5 Hz, 1H), 8.41 (d, J = 8.0 Hz,
G
https://dx.doi.org/10.1021/acs.joc.0c01979
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Nunez, M. G.; Farley, A. J. M.; Dixon, D. J. Bifunctional
Iminophosphorane Organocatalysts for Enantioselective Synthesis:
Application to the Ketimine Nitro-Mannich Reaction. J. Am. Chem.
Soc. 2013, 135, 16348.
orcid.org/0000-0002-5489-9555; Email: wongp2577@
gmail.com; Fax: (+) 66-53-892277
Authors
(4) Staudinger, H.; Meyer, J. New organic compounds of
phosphorus. III. Phosphinemethylene derivatives and phosphinimines.
Helv. Chim. Acta 1919, 2, 635.
Mookda Pattarawarapan − Department of Chemistry, Faculty
of Science and Research Center on Chemistry for Development
of Health Promoting Products from Northern Resources, Faculty
of Science, Chiang Mai University, Chiang Mai 50200,
Thailand; orcid.org/0000-0002-7484-122X
Dolnapa Yamano − Department of Chemistry, Faculty of
Science, Chiang Mai University, Chiang Mai 50200, Thailand
Nittaya Wiriya − Department of Chemistry, Faculty of Science,
Chiang Mai University, Chiang Mai 50200, Thailand
Saranphong Yimklan − Department of Chemistry, Faculty of
Science, Chiang Mai University, Chiang Mai 50200, Thailand
(5) Eguchi, S. Recent progress in the synthesis of heterocyclic
natural products by the Staudinger/intramolecular aza-wittig reaction.
ARKIVOC 2005, 2005, 98. Gololobov, Y. G.; Kasukhin, L. F. Recent
advances in the Staudinger reaction. Tetrahedron 1992, 48, 1353. van
Berkel, S. S.; van Eldijk, M. B.; van Hest, J. C. M. Staudinger Ligation
as a Method for Bioconjugation. Angew. Chem., Int. Ed. 2011, 50,
8806. Hartung, R.; Paquette, L. Recent synthetic applications of the
tandem Staudinger/Aza-Wittig reaction. Chemtracts 2004, 17, 72.
(6) Omran, O. A.; Sayed, S. M.; Raslan, M. A. Iminophosphoranes in
Heterocyclic Synthesis: A Facile Synthesis of Pyrido[4,3-D]-
Pyrimidine and Pyrido[4,3-D][1,3]Oxazine Derivatives via Intermo-
lecular aza-Wittig Reactions. J. Heterocycl. Chem. 2017, 54, 1103.
Alvarez-Sarandes, R.; Peinador, C.; Quintela, J. M. Iminophosphor-
anes in heterocyclic chemistry. A simple one-pot synthesis of
pyridothienopyridazines and pyrimidothienopyridazines. Tetrahedron
2001, 57, 5413. Zeng, F.; Alper, H. Tandem Palladium-Catalyzed
Addition/Cyclocarbonylation: An Efficient Synthesis of 2-Hetero-
quinazolin-4(3H)-ones. Org. Lett. 2010, 12, 1188.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c01979
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work is partially supported by Chiang Mai University,
Thailand, and The Thailand Research Fund through the Royal
Golden Jubilee Ph.D. Program (Grant No. PHD/0023/2559
to D.Y. and PHD/0072/2559 to N.W.). Special appreciation
to Chulabhorn Research Institute (CRI), Thailand, for the
HRMS analysis.
(7) Adib, M.; Sheikhi, E.; Deljoush, A. Reaction between
triphenylphosphine and aromatic amines in the presence of diethyl
azodicarboxylate: an efficient synthesis of aryliminophosphoranes
under neutral and mild conditions. Tetrahedron 2011, 67, 4137.
(8) Yavari, I.; Adib, M.; Hojabri, L. Vinyltriphenylphosphonium salt
mediated serendipitous synthesis of aryliminophosphoranes. Tetrahe-
dron 2002, 58, 7213.
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