Hydrosilane-Assisted Synthesis of Urea Derivatives from CO2and Amines

Article abstract of DOI:10.1021/acs.joc.0c02032

A methodology employing CO2, amines, and phenylsilane was discussed to access aryl- or alkyl-substituted urea derivatives. This procedure was characterized by adopting hydrosilane to promote the formation of ureas directly, without the need to prepare silylamines in advance. Control reactions suggested that FeCl3 was a favorable additive for the generation of ureas, and this 1,5,7-triazabicyclo[4.4.0]dec-5-ene-catalyzed reaction might proceed through nucleophilic addition, silicon migration, and the subsequent formal substitution of silylcarbamate.

Full text of DOI:10.1021/acs.joc.0c02032

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Hydrosilane-Assisted Synthesis of Urea Derivatives from CO2 and
Amines
Yulei Zhao,*,∥ Xuqiang Guo,∥ Zhiyao Si, Yanan Hu, Ying Sun, Yunlin Liu, Zhongyin Ji, and Jinmao You*
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ABSTRACT: A methodology employing CO2, amines, and
phenylsilane was discussed to access aryl- or alkyl-substituted
urea derivatives. This procedure was characterized by adopting
hydrosilane to promote the formation of ureas directly, without the
need to prepare silylamines in advance. Control reactions suggested
that FeCl3 was a favorable additive for the generation of ureas, and this 1,5,7-triazabicyclo[4.4.0]dec-5-ene-catalyzed reaction might
proceed through nucleophilic addition, silicon migration, and the subsequent formal substitution of silylcarbamate.
Scheme 1. Application of Silane in CO2 Conversion
rea and its derivatives are important industrial raw
materials and chemical intermediates. A range of
U
pharmaceuticals, plant growth regulators, herbicides, guanidi-
nate ligands, and asymmetric catalysts can be synthesized from
ureas.1 Despite the importance of ureas and its scale of annual
production, their industrial synthesis mainly depends on the
reaction of amines with toxic phosgene or its equivalents.2
Alternatively, the traditional synthesis of ureas also involves the
reaction of amines with isocyanates3 or CO.4 Inevitably, these
traditional synthesis methods can cause environmental and
toxicological problems to some extent. In recent years, many
transition metals (e.g., Pd,5 Mn,6 W,7 Au,8 Ni,9 Ru,10 Co11)
catalyzed reactions have been gradually exploited for urea
synthesis. Nevertheless, in order to develop an environmentally
friendly synthesis method of ureas, the use of readily available
raw materials is still a research direction that deserves more
attention.
As a building block in the synthesis of urea derivatives,
carbon dioxide (CO2) refers to a nontoxic, renewable, and
abundant one-carbon (C1) source, so the utilization of CO2
gained much attention during the past decades.12 The direct
synthesis of urea derivatives using CO2 and amines is usually
performed at high temperature (130−170 °C) or high pressure
(14−140 atm) environments.13 In order to improve the
synthesis of ureas, a series of effective reactions have been
developed, with CO2 as the raw material (such as ionic
liquid,14 Au,15 Cs,16 and Ce catalysis17).
Recently, silanes and amines or silylamines have been used
as starting materials to realize the conversion of CO2 to ureas,
which has attracted the attention of chemists. In 2016, Choi’s
group applied Zn(OAc)2/phen as catalyst for the synthesis of
carbamates from amines, CO2, and silicate esters (Scheme
1a).18 Later, they further developed a superbase-derived protic
ionic liquid catalyzed reaction to synthesize carbamate from
amines, CO2, and silicate esters.19 In these two studies, N,N′-
disubstituted urea was captured as a minor product. Different
from the reaction of silylamines and supercritical CO2 (140
atm) to furnish ureas,13d Stephan and co-workers demon-
strated a novel In-catalyzed reaction of pre-prepared silyl-
amines with CO2 (3 atm) to furnish ureas (Scheme 1b)20 in
2017. Subsequently, an elegant synthesis method of urea
Received: August 22, 2020
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© XXXX American Chemical Society
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A

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Note
a
derivatives from CO2 (2−5 atm) and pre-prepared silylamines
only with pyridine as the solvent was further developed by
Stephan’s group.21 Notably, Beller22 reported the methylation
of amines combined with CO2 (138 atm) and PhSiH3
(Scheme 1c), and excess silane was indispensable for their
methylation conversion. Combined with the above researches,
we envisage that perhaps it is possible to introduce an
appropriate amount of suitable silane to directly promote the
reaction of CO2 and amine for the formation of urea
derivatives.
Table 1. Optimization of the Reaction Conditions
During the course of our ongoing program on the
development of a methodology for the construction of
heterocyclic molecules,23 we developed a tandem methylena-
tion−cyclization reaction, involving enaminone, primary
aromatic amines, and two molecules of CO2, to access
tetrahydropyrimidines (Scheme 1d).23a In this process, we
discovered a new method for the formation of urea in the
presence of amine, CO2 (1 atm), and an appropriate amount of
hydrosilane (Scheme 1e).
First, it was discovered that 1,3-diphenylurea was formed in
93% yield at 110 °C upon treatment of the model substrates
(1a and CO2) with 10 mol % of FeCl3 and 1,5,7-
triazabicyclo[4.4.0]dec-5-ene (TBD) in THF (Table 1, entry
1, PhSiH3 1.5 equiv). When the amount of phenylsilane was
reduced, the yield decreased as well (entries 2−4). Using 1.2
equiv of phenylsilane could still obtain 2a with excellent yield;
therefore, we decided to use 1.2 equiv of phenylsilane for
follow-up investigations. At 90 °C, only a small amount of 2a
was obtained (entry 5, 24%). This result suggests that the
reaction might proceed by the thermal access. Using other
solvents (e.g., 1,4-dioxane, acetonitrile, and DMF) instead of
THF could not give better results (entries 6−8), although
acetonitrile and 1,4-dioxane also looked suitable for this
reaction. Other common silanes, such as Ph2SiH2, Ph3SiH,
Et3SiH, and polymethylhydrosiloxane (PMHS), could not
effectively promote the formation of 2a. This may be related to
the reduction ability of hydrosilane.24 The influence of the
catalyst on the reaction is also huge. When TBD was changed
to glycine betaine (GB), 1,4-diazabicyclo[2.2.2]octane
(DABCO), or pyridine, almost no target product was
observed. For this transformation, 4-dimethylaminopyridine
(DMAP) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was
efficient, leading to 2a in 39% or 73% yield, respectively. Next,
other acid catalysts were investigated (entries 19−23).
However, only AgNO3 could display a good catalytic effect
(entry 23, 86%), while the yield was not as good as that
catalyzed by FeCl3 (entry 2). So, the optimal reaction
conditions for the preparation of 2a included 10 mol % of
TBD and FeCl3 as the catalysts and 1.2 equiv of phenylsilane
as the additive at 110 °C in THF. In addition, it is worth
noting that, when the amount of FeCl3 and TBD dropped from
0.1 to 0.05 equiv, 2a could also be obtained in 90% yield (entry
24: it will take longer).
a
Reaction conditions: CO2 (1 atm), 1a (0.75 mmol), 3 mL of THF as
b
c
solvent. Isolated yield, ND = no detected. The reaction was carried
out at 90 °C.
chloride, 2a was only isolated in 38% yield. This shows that
ferric chloride is a favorable additive for the formation of ureas.
With the standard reaction conditions in hand (Table 1,
entry 2) and by employing a variety of amines, the substrate
scope of the reaction was explored. As shown in Table 2, the
ureas derived from primary amines were obtained in good
yields regardless of the nature of the substituents. Aniline
derivatives bearing electron-donating (e.g., 4-NMe2, 4-OMe,
3,4-dimethoxy, and 3,4,5-trimethoxy) groups were suitable for
the reaction, offering the corresponding ureas 2b−2e in good
yields. Alkyl-substituted phenyl was also compatible (2f−2h,
80−86%), even bearing sterically hindered tert-butylphenyl
group. The substrates with electron-withdrawing (e.g., R = p-
FPh, p-ClPh, p-BrPh, p-CO2Et, p-CF3) groups were also
tolerable to furnish corresponding aryl-substituted urea
derivatives (2i−2m, 69−82%). It is noteworthy that, when R
was an alkyl substituent (such as, benzyl, N-butyl, and
In order to verify the necessity of each component, several
control experiments were carried out (entries 25−27). Without
PhSiH3, no 2a was obtained (entry 25 vs entry 2), indicating
that PhSiH3 was crucial for the formation of urea derivatives.
When the reaction was conducted in the absence of TBD, the
corresponding urea 2a could not be observed (entry 3).
Combined with existing reports,25 this result revealed that
TBD’s activation to CO2 is indispensable. A suitable Lewis acid
catalyst is also required. To perform the reaction without ferric
B
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a
Table 2. Scope of the Reaction
a
b
c
d
The reactions were carried out under the optimized reaction conditions. Isolated yield. 1.5 equiv of PhSiH3 was used. No 2s was obtained, but
further N-formylation product was observed.
Figure 1. Proposed reaction mechanism.
cyclohexyl groups), the corresponding products were also
obtained in good yields (2n−2p). The indole group could be
introduced by adopting tryptamine (e.g., 5-methoxytrypt-
amine) as starting material (2q, 73%), and the N-H part of
the indole was compatible with the reaction. Treatment of
sterically hindered o-toluidine under the standard reaction
conditions furnished 2r in 71% yield. An intramolecular
cyclization reaction of 2-(aminomethyl)aniline 1s and CO2 did
not furnish 2s, but a further N-formylation product (from 2s)
was observed, which is being investigated in our laboratory.
C
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Note
When different amines are used simultaneously (e.g., 1c:1o =
1:1), 2c, 2o, and unsymmetric 1-butyl-3-(4-methoxyphenyl)-
urea were obtained as a mixture. It is worth noting that
secondary amines (such as N-methylaniline and dibenzyl-
amine) were not suitable to form ureas. The structure of the
products was ascertained by nuclear magnetic resonance
analysis and further confirmed by X-ray analysis of 2a.26
Next, the reaction mechanism was explored and studied.
Since the cross-dehydrocoupling of hydrosilanes with amines
has been implemented,27 we speculate that the corresponding
silylamine may also be generated as the initial intermediate at
high temperature in our reaction. Moreover, the pre-prepared
silylamines (e.g., RNH(SiMe3)) reacted with CO2 to prepare
ureas and disilyl-ether (e.g., (Me3Si)2O), which has been
proposed by Stephan21 (through a key silylcarbamate
intermediate). Therefore, a seemingly feasible reaction path
through the silylamine and silylcarbamate intermediates was
presented to us. To further support this inference, ESI-MS
analysis28 was performed during the reaction process. After the
reaction (1a with PhSiH3 and CO2, under the standard
conditions) had progressed for 5 h, a sample was taken from
the reaction mixture for ESI-MS analysis. Fortunately, the
characteristic signals of the possible silylcarbamate PhNHCO2-
SiH2Ph and disilyl-ether (PhH2Si)2O were observed (see
Figure S1), which suggests silylcarbamate may be a possible
intermediate and implies the generation of disilyl-ether during
the reaction process. It should be pointed out that, although
we attempted to capture or isolate the possible, unstable
silylamines,29 no significant and clean products were observed.
The remaining silicon−hydrogen bond may cause further
transformation, which leads to the difficulty of separation of
the corresponding intermediate.
nucleophilic addition of CO2 with silylamine, silicon migration,
and the subsequent formal substitution of silylcarbamate.
Further investigations on the detailed reaction mechanism are
in progress.
EXPERIMENTAL SECTION
■
General Methods. All reactions were carried out in carbon
dioxide except noted. Anhydrous 1,4-dioxane and tetrahydrofuran
were distilled from sodium and benzophenone. Anhydrous acetoni-
trile and DMF were prepared by distillation from CaH2. Compounds
1a−1s were purchased from Energy Chemical (Shanghai) Co. Ltd.
Commercially, available reagents were used without further
purification. Reactions were monitored by thin layer chromatography
using UV light to visualize the course of reaction. Purification of
reaction products was carried out by flash chromatography on silica
1
gel (300−400 mesh). H NMR spectra were recorded at 500 or 400
MHz; 13C NMR spectra were recorded at 125 or 100 MHz, and in
1
CDCl3 or (CD3)2SO (containing 0.03% TMS) solutions. H NMR
spectra were recorded with Me4Si (δ = 0.00) as the internal reference,
and 13C NMR spectra were recorded with CDCl3 (δ = 77.00) or
DMSO-d6 (δ = 39.52) as the internal reference. High-resolution mass
spectra were obtained using a Bruker Maxis Impact mass spectrometer
with a TOF (for ESI) analyzer. Single crystal X-ray diffraction data
were collected in Bruker SMARTAPEX diffractometers with
molybdenum cathodes.
Synthesis and Characterization of 2. To a well-dried 25 mL
seal tube containing a magnetic stirring bar was added TBD (10.4 mg,
0.075 mmol). Then, the vessel was evacuated and refilled with CO2
for five times. Under a stream of CO2, to this vessel were added amine
(0.75 mmol), THF (2.0 mL), PhSiH3 (111 μL, 0.9 mmol), and FeCl3
(12 mg, 0.075 mmol). Then the vessel was sealed at atmospheric
pressure of CO2 (1 atm), and the resulting mixture was stirred in a
110 °C oil bath for the corresponding time (see Table 2). The
reaction could be monitored by TLC analysis. The resulting mixture
was concentrated under reduced pressure and subjected to column
chromatography for purification directly.
On the basis of the above results and the well reported
literatures, the possible reaction mechanism is depicted in
Figure 1. Initially, cross-dehydrocoupling of hydrosilane with
amines occurs to form silylamine I.27 Subsequently, under the
activation of hydrogen bond interaction, intermediate II is
generated through the nucleophilic addition between CO2 and
1,3-Diphenylurea20 (2a). White solid; 92% yield (73 mg), Rf = 0.2
1
(petroleum ether/ethyl acetate = 5/1); mp: 229−230 °C; H NMR
(500 MHz, DMSO-d6): δ 8.64 (s, 2H), 7.45 (d, J = 7.9 Hz, 4H),
7.29−7.26 (m, 4H), 6.98−6.95 (m, 2H); 13C{1H} NMR (125 MHz,
DMSO-d6): δ 152.5, 139.7, 128.8, 121.8, 118.2.
I.25 The Nsp atom of TBD, as a Brønsted base, may grab the H
2
1,3-Bis(4-(dimethylamino)phenyl)urea20 (2b). Yellow solid; 84%
yield (94 mg), Rf = 0.2 (petroleum ether/ethyl acetate = 1/1); mp:
atom of silylamine I to facilitate this process. This similar
catalytic process has also been suggested by Wang25a and
Cantat25b in TBD-catalyzed reactions of amines with CO2.
Next, after a silicon migration,21 II is converted to intermediate
III that further undergoes proton migration to afford
silylcarbamates IV. Finally, a formal substitution process (IV
to 2)20,21 between IV and additional silylamine I proceeds to
form ureas. In this procedure, ferric chloride, as a beneficial
additive, may coordinate with the carbonyl group to enhance
its electrophilicity,30 which may promote the corresponding
nucleophilic addition or substitution. Alternatively, the
addition of amine 1 and CO2, followed by coupling with
hydrosilane to form IV, might also be involved during the
reaction.
1
236−238 °C; H NMR (500 MHz, DMSO-d6): δ 8.13 (s, 2H), 7.24
(d, J = 9.0 Hz, 4H), 6.68 (d, J = 8.9 Hz, 4H), 2.82 (s, 12H); 13C{1H}
NMR (125 MHz, DMSO-d6): δ 153.1, 146.2, 130.0, 119.9, 113.2,
40.8.
1,3-Bis(4-methoxyphenyl)urea20 (2c). White solid; 81% yield (83
mg), Rf = 0.2 (petroleum ether/ethyl acetate = 2/1); mp: 238−240
°C; 1H NMR (500 MHz, DMSO-d6): δ 8.36 (s, 2H), 7.34 (d, J = 9.0
Hz, 4H), 6.85 (d, J = 8.9 Hz, 4H), 3.71 (s, 6H); 13C{1H} NMR (125
MHz, DMSO-d6): δ 154.3, 152.9, 132.9, 119.9, 114.0, 55.2.
1,3-Bis(3,4-dimethoxyphenyl)urea31 (2d). Yellow solid; 88% yield
(110 mg), Rf = 0.2 (petroleum ether/ethyl acetate = 1/1); mp: 206−
1
208 °C; H NMR (500 MHz, DMSO-d6): δ 8.40 (s, 2H), 7.19 (s,
2H), 6.86 (s, 4H), 3.74 (s, 6H), 3.71 (s, 6H); 13C{1H} NMR (125
MHz, DMSO-d6): δ 152.8, 148.8, 143.9, 133.5, 112.5, 110.1, 103.9,
55.9, 55.4; HRMS (ESI) m/z: [M + H]+ Calcd for C17H21N2O5
333.1445; Found 333.1452.
CONCLUSION
■
1,3-Bis(3,4,5-trimethoxyphenyl)urea (2e). Yellow solid; 76% yield
(112 mg), Rf = 0.2 (petroleum ether/ethyl acetate = 1/1); mp: 164−
In summary, we herein report on the reaction of CO2 with
amines and phenylsilane to furnish aryl- or alkyl-substituted
urea derivatives. The characteristic of this synthetic method of
ureas is to utilize silane directly, without the need to prepare
silylamine in advance. Control experiments revealed that
phenylsilane was indispensable and ferric chloride was a
favorable additive for the formation of ureas. This TBD-
catalyzed multicomponent reaction might proceed through
1
165 °C; H NMR (500 MHz, DMSO-d6): δ 8.54 (s, 2H), 6.78 (s,
4H), 3.76 (s, 12H), 3.61 (s, 6H); 13C{1H} NMR (125 MHz, DMSO-
d6): δ 152.9, 152.5, 135.8, 132.5, 96.1, 60.1, 55.7; HRMS (ESI) m/z:
[M + H]+ Calcd for C19H25N2O7 393.1656; Found 393.1651.
1,3-Di-p-tolylurea20 (2f). Yellow solid; 83% yield (75 mg), Rf = 0.2
1
(petroleum ether/ethyl acetate = 8/1); mp: 243−245 °C; H NMR
(500 MHz, DMSO-d6): δ 8.49 (s, 2H), 7.32 (d, J = 8.4 Hz, 4H), 7.07
D
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(d, J = 8.2 Hz, 4H), 2.24 (s, 6H); 13C{1H} NMR (125 MHz, DMSO-
d6): δ 152.6, 137.2, 130.5, 129.1, 118.2, 20.3.
(500 MHz, DMSO-d6): δ 8.25 (s, 2H), 7.81 (d, J = 8.0 Hz, 2H),
7.19−7.13 (m, 4H), 6.97−6.94 (m, 2H), 2.27 (s, 6H); 13C{1H} NMR
(125 MHz, DMSO-d6): δ 153.0, 137.5, 130.2, 127.7, 126.1, 122.7,
121.5, 18.1.
1,3-Bis(4-ethylphenyl)urea (2g). White solid; 80% yield (81 mg),
Rf = 0.2 (petroleum ether/ethyl acetate = 8/1); mp: 218−220 °C; 1H
NMR (500 MHz, DMSO-d6): δ 8.50 (s, 2H), 7.34 (d, J = 8.4 Hz,
4H), 7.10 (d, J = 8.3 Hz, 4H), 2.54 (q, J = 7.5 Hz, 4H), 1.15 (t, J = 7.6
Hz, 6H); 13C{1H} NMR (125 MHz, DMSO-d6): δ 152.6, 137.4,
137.0, 127.9, 118.3, 27.5, 15.8; HRMS (ESI) m/z: [M + H]+ Calcd
for C17H21N2O 269.1648; Found 269.1650.
Gram-Scale Preparation (for 2a). To a well-dried 250 mL seal
tube containing a magnetic stirring bar was added TBD (0.1044 g,
0.75 mmol). Then, the vessel was evacuated and refilled with CO2 for
five times. Under a stream of CO2, to this vessel were added THF (20
mL), PhNH2(0.68 mL, 7.5 mmol), PhSiH3(1.1 mL, 9.0 mmol), and
FeCl3 (0.12 g, 0.75 mmol). Then the vessel was sealed at atmospheric
pressure of CO2 (1 atm), and the resulting mixture was stirred in a
110 °C oil bath for 36 h. The reaction could be monitored by TLC
analysis. The resulting mixture was concentrated under reduced
pressure. The resulting residue was subjected to column chromatog-
raphy for purification (petroleum ether/ethyl acetate = 5:1) to give
pure 2a (0.65 g, 82%).
1,3-Bis(4-(tert-butyl)phenyl)urea31 (2h). White solid; 86% yield
(105 mg), Rf = 0.2 (petroleum ether/ethyl acetate = 10/1); mp: 267−
268 °C; 1H NMR (500 MHz, DMSO-d6): δ 8.51 (s, 2H), 7.36 (d, J =
8.6 Hz, 4H), 7.28 (d, J = 8.6 Hz, 4H), 1.26 (s, 18H); 13C{1H} NMR
(125 MHz, DMSO-d6): δ 152.6, 144.0, 137.1, 125.3, 118.0, 33.9, 31.3.
1,3-Bis(4-fluorophenyl)urea31 (2i). Yellow solid; 69% yield (64
mg), Rf = 0.2 (petroleum ether/ethyl acetate = 5/1); mp: 260−262
°C; 1H NMR (500 MHz, DMSO-d6): δ 8.78 (s, 2H), 7.48−7.45 (m,
4H), 7.14−7.10 (m, 4H); 13C{1H} NMR (125 MHz, DMSO-d6): δ
157.3 (d, J = 236.6 Hz), 152.8, 136.1 (d, J = 2.3 Hz), 120.0 (d, J = 7.6
Hz), 115.3 (d, J = 22.1 Hz).
ASSOCIATED CONTENT
■
sı
* Supporting Information
1,3-Bis(4-chlorophenyl)urea20 (2j). Yellow solid; 82% yield (86
mg), Rf = 0.2 (petroleum ether/ethyl acetate = 5/1); mp: 245−247
°C; 1H NMR (500 MHz, DMSO-d6): δ 8.85 (s, 2H), 7.48 (d, J = 8.9
Hz, 4H), 7.33 (d, J = 8.8 Hz, 4H); 13C{1H} NMR (125 MHz,
DMSO-d6): δ 152.3, 138.5, 128.6, 125.5, 119.8.
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02032.
1H and 13C NMR spectra for compounds 2 (PDF)
Crystallographic details for compound 2a (CIF)
1,3-Bis(4-bromophenyl)urea20 (2k). White solid; 78% yield (108
mg), Rf = 0.2 (petroleum ether/ethyl acetate = 5/1); mp: 292−294
°C; 1H NMR (500 MHz, DMSO-d6): δ 8.86 (s, 2H), 7.46−7.42 (m,
8H); 13C{1H} NMR (125 MHz, DMSO-d6): δ 152.3, 139.0, 131.5,
120.2, 113.4.
AUTHOR INFORMATION
Corresponding Authors
■
Yulei Zhao − School of Chemistry and Chemical Engineering,
Qufu Normal University, Qufu 273165, China; orcid.org/
0000-0002-8628-2680; Email: zhaoyulei86@126.com
Jinmao You − School of Chemistry and Chemical Engineering,
Qufu Normal University, Qufu 273165, China; Northwest
Institute of Plateau Biology, Chinese Academy of Science, Xining
810001, China; Email: jmyou6304@163.com
Diethyl 4,4′-(Carbonylbis(azanediyl))dibenzoate32 (2l). White
solid; 73% yield (98 mg), Rf = 0.2 (petroleum ether/ethyl acetate =
1
3/1); mp: 211−213 °C; H NMR (400 MHz, DMSO-d6): δ 9.19 (s,
2H), 7.90 (d, J = 8.8 Hz, 4H), 7.60 (d, J = 8.8 Hz, 4H), 4.28 (q, J =
7.1 Hz, 4H), 1.30 (t, J = 7.1 Hz, 6H); 13C{1H} NMR (100 MHz,
DMSO-d6): δ 165.9, 152.3, 144.4, 130.8, 123.6, 118.0, 60.8, 14.7.
1,3-Bis(4-(trifluoromethyl)phenyl)urea33 (2m). White solid; 69%
yield (90 mg), Rf = 0.2 (petroleum ether/ethyl acetate = 5/1); mp:
228−230 °C; 1H NMR (400 MHz, DMSO-d6): δ 9.22 (s, 2H), 7.70−
7.64 (m, 8H); 13C{1H} NMR (100 MHz, DMSO-d6): δ 152.1, 143.1,
126.1, 124.5 (q, J = 269.5 Hz), 122.2 (q, J = 32.2 Hz), 118.1.
1,3-Dibenzylurea21 (2n). White solid; 72% yield (65 mg), Rf = 0.2
Authors
Xuqiang Guo − School of Chemistry and Chemical Engineering,
Qufu Normal University, Qufu 273165, China
Zhiyao Si − School of Chemistry and Chemical Engineering,
Qufu Normal University, Qufu 273165, China
Yanan Hu − School of Chemistry and Chemical Engineering,
Qufu Normal University, Qufu 273165, China
Ying Sun − School of Chemistry and Chemical Engineering, Qufu
Normal University, Qufu 273165, China
Yunlin Liu − School of Chemistry and Chemical Engineering,
Guangzhou University, Guangzhou 510006, China;
orcid.org/0000-0001-5902-9885
Zhongyin Ji − School of Chemistry and Chemical Engineering,
Qufu Normal University, Qufu 273165, China
1
(petroleum ether/ethyl acetate = 5/1); mp: 157−159 °C; H NMR
(500 MHz, DMSO-d6): δ 7.31−7.22 (m, 10H), 6.43 (s, 2H), 4.24 (d,
J = 3.4 Hz, 4H); 13C{1H} NMR (125 MHz, DMSO-d6): δ 158.1,
140.9, 128.2, 127.0, 126.6, 43.0.
1,3-Dibutylurea34 (2o). White solid; 75% yield (48 mg), Rf = 0.3
(petroleum ether/ethyl acetate/dichloromethane = 7/1/2); mp: 71−
72 °C; 1H NMR (500 MHz, CDCl3): δ 4.69 (s, br, 2H), 3.15 (t, J =
7.1 Hz, 4H), 1.50−1.44 (m, 4H), 1.38−1.31 (m, 4H), 0.92 (t, J = 7.4
Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3): δ 158.7, 40.2, 32.3,
20.0, 13.8.
1,3-Dicyclohexylurea35 (2p). White solid; 68% yield (60 mg), Rf =
0.3 (petroleum ether/ethyl acetate/dichloromethane = 7/1/2); mp:
1
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02032
224−226 °C; H NMR (400 MHz, DMSO-d6): δ 5.57 (s, br, 2H),
3.52−3.25 (m, 2H), 1.72−1.51 (m, 10H), 1.25−1.06 (m, 10H);
13C{1H} NMR (100 MHz, DMSO-d6): δ 47.5, 33.3, 25.3, 24.4 (due
to poor solubility, carbon atom in carbonyl group is not shown);
HRMS (ESI) m/z: [M + H]+ Calcd for C13H25N2O 225.1961; Found
225.1964.
Author Contributions
∥Y.Z. and X.G. contributed equally to this work.
Notes
1,3-Bis(2-(5-methoxy-1H-indol-3-yl)ethyl)urea (2q). Colorless oil;
1
The authors declare no competing financial interest.
73% yield (111 mg), Rf = 0.2 (ethyl acetate); H NMR (500 MHz,
CDCl3): δ 8.11 (s, 2H), 7.20 (d, J = 8.8 Hz, 2H), 7.05−6.93 (m, 2H),
6.84−6.83 (m, 4H), 4.37 (s, br, 2H), 3.82 (s, 6H), 3.39 (t, J = 6.3 Hz,
4H), 2.82 (t, J = 6.4 Hz, 4H); 13C{1H} NMR (125 MHz, CDCl3): δ
153.9, 131.5, 127.7, 123.1, 112.6, 112.1, 112.0, 100.6, 55.9, 40.6, 25.7;
HRMS (ESI) m/z: [M + H]+ Calcd for C23H27N4O3 407.2078;
Found 407.2083.
ACKNOWLEDGMENTS
■
This work was financially supported by the Natural Science
Foundation of Shandong Province (No. ZR2018BB026) and
the Doctoral Start-Up Scientific Research Foundation of Qufu
Normal University. This paper is dedicated to Zhao’s
upcoming child.
1,3-Di-o-tolylurea36 (2r). White solid; 71% yield (64 mg), Rf = 0.2
1
(petroleum ether/ethyl acetate = 5/1); mp 235−237 °C; H NMR
E
https://dx.doi.org/10.1021/acs.joc.0c02032
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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