Spontaneous and direct transformation of N,O-diaryl carbamates into N,N′-diarylureas

Article abstract of DOI:10.1248/cpb.c18-00394

We have discovered a spontaneous reaction of N,O-diaryl carbamates to afford symmetrical N,N′-diarylureas. Optimization of the conditions indicated that N,N-dimethylformamide (DMF) was the best solvent and triethylamine (Et₃N) was the best additive for this transformation. The reaction requires the presence of aryl groups on the nitrogen and oxygen atoms of carbamates. Substrates bearing an electron-donating methoxy group on either of the aryl groups reacted slowly under these conditions.

Full text of DOI:10.1248/cpb.c18-00394

880
Chem. Pharm. Bull. 66, 880–884 (2018)
Vol. 66, No. 9
Regular Article
Spontaneous and Direct Transformation of N,O-Diaryl Carbamates into
N,N′-Diarylureas
Ryu Yamasaki,* Yutaka Honjo, Ai Ito, Kazuo Fukuda, and Iwao Okamoto
Showa Pharmaceutical University; 3–3165 Higashi-Tamagawagakuen, Machida, Tokyo 194–8543, Japan.
Received May 24, 2018; accepted June 18, 2018
We have discovered a spontaneous reaction of N,O-diaryl carbamates to afford symmetrical N,N′-
diarylureas. Optimization of the conditions indicated that N,N-dimethylformamide (DMF) was the best
solvent and triethylamine (Et3N) was the best additive for this transformation. The reaction requires the
presence of aryl groups on the nitrogen and oxygen atoms of carbamates. Substrates bearing an electron-
donating methoxy group on either of the aryl groups reacted slowly under these conditions.
Key words carbamate; N,N′-diphenylurea; triethylamine (Et3N); isocyanate
The N,N′-diphenylurea skeleton is found in many biologi-
Results and Discussion
To examine the direct transformation of N,O-diaryl car-
cally active compounds, including cytokinin,1) antischistosom-
al agent,2) diacylglycerol acyltransferase (DGAT)1 inhibitor,3) bamate to symmetrical N,N′-diarylurea, we chose N-(4-
vascular endothelial growth factor receptor (VEGFR)-2 in- methylphenyl)-O-phenyl carbamate (1) as a model substrate
hibitor,4) BKca channel activator,5) and p-38-mitogen-activated (Table 1). We were pleased to find that 1 afforded N,N′-bis(4-
protein (MAP) kinase inhibitor.6) In addition, N,N′-diphenyl- methylphenyl)urea (2) in 91% yield in the presence of 1 equiv
substituted urea derivatives are useful components for gel- of Et3N in N,N-dimethylformamide (DMF) (Table 1, entry 1)
forming materials7) and crystal engineering.8)
in open-air environment.21) When the reaction was performed
N,N′-Diphenylurea derivatives are typically synthesized at 50°C, the yield of 2 was decreased (Table 1 entry 2). Other
by reaction of amine with aryl isocyanates or phosgene,9) or less polar solvents, such as 1,4-dioxane, toluene, and dichloro-
with carbamates.10–14) Indeed, unsymmetrically substituted ethane also resulted in lower yield (Table 1, entries 3–5).
ureas can be prepared from carbamate by direct reaction with
The use of dimethyl sulfoxide (DMSO) as the solvent re-
amine.13–15) Analogously with the reaction of carbamates, sulted in the formation of a by-product, presumed to be the
N-arylcarbamates decompose to afford phenyl isocya- product of trimerization of isocyanate, and the yield of the
nate in the presence of triethylamine (Et3N) via the E1cB desired 2 was only 32% (Table 1, entry 6). Among other polar
mechanism10) (Fig. 1a). In addition, phenyl isocyanate affords
N,N′-diphenylurea even in the absence of amine16–18) (Fig.
Table 1. Optimization of Conditions for Direct Transformation
1b). However, carbamates have been known as a “blocked
isocyanate,”19) there are few examples of the synthesis of urea
compounds via carbamate with a single-pot operation (Fig.
1c); a precedent required high temperature (200°C) and did
not report isolated yield of urea.20) Such reactions would be
useful, considering the difficulty of handling highly reactive
Yield of 2
aryl isocyanates. Here, we report a spontaneous, single-step
formation of symmetrical N,N′-diarylurea compounds from
N,O-diaryl carbamates.
Entry
Additive (eq)
Et3N (1)
Solvent
DMF
Time (h)
(%)a)
1
2b)
3
25
23
91
71
55
28
45
32
38
45
95
93
82
75
89
83
95
Et3N (1)
DMF
Et3N (1)
1,4-Dioxane
Toluene
ClCH2CH2Cl
DMSO
DMA
96
4
Et3N (1)
121
65
5
Et3N (1)
6
Et3N (1)
32
7
Et3N (1)
52
8
Et3N (1)
NMP
44
9
Et3N (1)
DMI
30
10
11
12
13
14
15
Et3N (0.01)
None
DMF
24
DMF
70
DMAP (0.01)
2,6-Lutidine (0.01)
Imidazole (0.01)
TMEDA (0.01)
DMF
116
71
DMF
DMF
67
DMF
50
a) Isolated yield. Yields were calculated based on the assumption that 2eq of aryl
carbamate was consumed to generate 1eq of aryl urea. b) The reaction was performed
at 50°C.
Fig. 1. Reactions of N,O-Diaryl Carbamate and Aryl Isocyanate
*To whom correspondence should be addressed. e-mail: yamaryu@ac.shoyaku.ac.jp
© 2018 The Pharmaceutical Society of Japan

Vol. 66, No. 9 (2018)
Chem. Pharm. Bull.
881
Table 2. Substrate Scope of the Reaction
Time Yield
(h)
Entry Cmpd.
R1
R2
(%)a)
1
2
3
4
5
6
3a
3b
3c
3d
3e
3f
4-Nitrophenyl
C6H5
27
44
96
20
44
97
87
75
0
4-Methoxyphenyl C6H5
Benzyl
C6H5
C6H5
C6H5
C6H5
4-Nitrophenyl
4-Methoxyphenyl
Methyl
91
80
2
a) Isolated yield.
non-protic solvents, 1,3-dimethylimidazolidinone (DMI) af-
forded 2 in 95% yield (Table 1, entries 7–9) after a slightly
longer reaction time. The reaction proceeded even with only a
catalytic amount of Et3N (1mol %), and afforded 2 in compa-
rable yield (Table 1, entry 10). The role of Et3N in accelerating
the reaction was highlighted by the reaction in the absence
of Et3N, which required a longer reaction time and afforded
only moderate yield (Table 1, entry 11). Other amine additives,
such as N,N-dimethylaminopyridine (DMAP), 2,6-lutidine,
imidazole, and tetramethylethylenediamine (TMEDA), were
less effective than Et3N, and required a longer reaction time to
attain a reasonable product yield (Table 1, entries 12–15).
With the optimized conditions in hand, we explored the
Fig. 2. Competitive Reactions
scope of the reaction (Table 2). When the reaction was per- compounds (Fig. 2a). It is noteworthy that compound 6 was
formed with 3a, which has an electron-withdrawing nitro not observed in the crude mixture. At this stage, we think low
group on the anilino group, the outcome of the reaction was nucleophilicity of p-nitroaniline generated from 3a might be a
comparable with that of 1 (entry 1). In contrast, the carbamate major reason that 6 was not observed. Similar reaction of 3d
bearing an electron-donating methoxy group on the anilino and 3g also resulted in a complex mixture of 2, 7, and 8 (ca.
1
group, 3b, reacted slowly under the same conditions, and the 2:7:8=1:2:1 based on the H-NMR of the crude mixture),
yield was moderate (entry 2). Replacement of the anilino together with other unidentified products (Fig. 2b). These re-
moiety with a benzyl group impeded the reaction, and the sults may imply that the reaction involves multiple steps.
desired diphenylurea product was not obtained (3c, entry 3);
To obtain mechanistic insight into the reaction, the carba-
most of the starting material was recovered. This result shows mate 3h was reacted with p-toluidine under the same condi-
the importance of the phenyl moiety for this direct trans- tions. An unsymmetrically substituted urea, 8 was obtained
formation. Replacement of the O-aryl moiety with various selectively in 90% yield within 1h (Fig. 3a) as expected from
substituted phenyl groups affected the yield of the correspond- literatures.22) The carbamate 3h was also reacted with p-tolyl
ing symmetrical diphenyl urea similarly; introduction of an isocyanate under the same conditions. Selectivity was low,
electron-withdrawing nitro group (3d) afforded a good yield and a complex mixture of 7, 8 and 2 (ca. 7:8:2=1:2:1 from
of N,N′-diphenylurea in a shorter reaction time, while the 1H-NMR of the crude mixture) and other impurities was ob-
electron-donating methoxy group (3e) required a longer reac- tained (Fig. 3b). A comparison of reactivity in Table 2 and
tion time to afford a comparable yield of the urea compound. product ratios in Figs. 2b and 3b suggests that the product-
When the O-aryl group was replaced with a methyl group determining step may be formation of aryl isocyanate, for
(3f), only a small amount of N,N′-diphenylurea was obtained which the presence of an electron-donating group would be
and most of the starting material, carbamate 3f, remained in- disadvantageous.
tact. These results indicate that the presence of an aryl group
To observe intermediates involved in the reaction, we moni-
on both nitrogen and oxygen of carbamate is required, and tored the reaction of 1 in the presence of 1mol % Et3N by
1
there is a preference for an electron-withdrawing substituent means of H-NMR in DMF-d7 in a sealed tube at 80°C (Fig.
on the phenyl group.
4). The reaction was slower, and carbamate was remained
The difference in the reactivity of various carbamates even after 24h, probably due to the lack of moisture in a
(3a–3d) in Table 2 led us to investigate selective formation sealed tube. Signals of carbamate 1 and 2 were observed in
of N,N′-diarylureas from a mixture of carbamates (Fig. 2); the Ph-CH3 region (ca. 2ppm), and those of p-tolyl isocyanate
compatibility with multiple reactive sites would be beneficial and p-toluidine were not detected. The absence of p-tolyl
for application to polymerization. A mixture of 3a and 3b isocyanate and p-toluidine peaks in the reaction mixture sug-
was reacted under similar conditions to those of Table 2, gests that the formation of aryl isocyanate and aniline from
affording a complex mixture of 4, 5 and other unidentified carbamate is slow (rate-limiting step) and/or that the equilib-

882
Chem. Pharm. Bull.
Vol. 66, No. 9 (2018)
selective coupling products from a mixture of carbamates,
apparently due to involvement of multiple intermediates in
the reaction. This reaction should be useful to synthesize
functional molecules with an N,N′-diphenylurea skeleton via
polymerization or cyclization by employing bench-stable N,O-
diaryl carbamate.
Experimental
General Melting points (mp) were determined by using a
Yanaco melting point apparatus MP-S3 and are uncorrected.
Fourier transform (FT)-IR spectra were recorded on a Horiba
1
FT-710. H- and 13C-NMR spectra were recorded on a JEOL
Fig. 3. Reactions of 3h with Amine or Isocyanate
AL-300 or ECZ400S or Bruker AV-300M, and chemical shifts
are expressed in parts per million relative to tetramethyl-
silane (TMS) or residual solvent peak (7.24ppm for CDCl3
(1H), 77.0ppm for CHCl3 (13C), 2.49ppm for DMSO-d6 (1H),
39.5ppm for DMSO-d6 (13C), 8.03ppm for DMF-d7 (1H)). Mass
spectra were measured on a JEOL MS700V or HX110. Silica
gel (CHROMATOREX PSQ100 (Fuji Silysia Chemical Co.,
Inc.)) was used for all chromatographic procedures.
Preparation of 1 Et3N (0.80mL, 5.7mmol) and phenyl
chloroformate (1.0mL, 7.9mmol) were added dropwise to a
solution of p-toluidine (1.00g, 9.3mmol) in CH2Cl2 (10mL)
under cooling in an ice bath. The mixture was stirred for 1h,
and then evaporated to dryness. The residue was recrystallized
from n-hexane to afford 1 (660mg, 51%) as colorless needles.
1H-NMR and mp were consistent with reported data.23)
Phenyl N-(4-Methylphenyl)carbamate (1)
Fig. 4. 1H-NMR Spectra Showing the Time Course of the Reaction
mp 119.0–120.0°C; 1H-NMR (300MHz, CDCl3) 2.33 (s,
3H), 7.13–7.24 (m, 5H), 7.32–7.42 (m, 4H).
General Procedure for the Reaction of 1 (Table 1) Et3N
(1.4 µL, 0.01mmol) was added to a solution of 1 (227mg,
1.0mmol) in DMF (4mL), and the mixture was stirred at
80°C without Ar displacement (open-air) until the reaction
was complete, as determined by TLC analysis. Then, Et2O
(200mL) was added, and the mixture was washed with sat.
NH4Cl aq. (200mL) and 10% NaOH aq. (200mL) twice, dried
over Na2SO4, and filtered. The filtrate was evaporated under
1
reduced pressure to afford 2 as a colorless powder. H-NMR
was consistent with reported data.24)
Chart 1. Proposed Reaction Mechanism
N,N′-Bis(4-methylphenyl)urea (2)
1H-NMR (300MHz, DMSO-d6) 2.22 (s, 6H), 7.06 (d,
rium between carbamate and isocyanate predominantly favors J=8.4Hz, 4H), 7.31 (d, J=8.4Hz, 4H), 8.49 (brs, 2H).
1
carbamate,17) so that isocyanate is undetectable by H-NMR.
Preparation of 3a Pyridine (0.77mL, 9.6mmol) and phe-
Based on the our findings and reported results,13,17) we nyl chloroformate (1.1mL, 8.8mmol) were added dropwise
propose the reaction mechanism depicted in Chart 1. NR3 (or to a solution of p-nitroaniline (1.11g, 8.0mmol) in CH2Cl2
Et3N) catalyzes the reaction of carbamate 3h to 9, which fa- (50mL), and the reaction mixture was stirred for 1h at room
vors 3h in the equilibrium. Phenyl isocyanate 9 can be hydro- temperature (r.t.). Then, 10% HCl (1mL) and H2O (40mL)
lyzed by residual H2O to form aniline 10, which in turn reacts were added. The organic layer was dried over Na2SO4, fil-
with 3h or 9 to afford N,N′-diphenylurea 7. Since absence of tered, and evaporated under reduced pressure. The crude
water, under a strict anhydrous condition, probably prevented product was purified by silica gel column chromatography
the formation of 10, and the reaction was not completed (cf. (eluent, AcOEt–hexane=1:3) to afford 3a as a yellow solid
1
Fig. 4).
(1.69g, 81%). H-NMR and mp were consistent with reported
data.25)
Phenyl N-(4-Nitrophenyl)carbamate (3a)
mp 158.0–159.0°C; 1H-NMR (300MHz, CDCl3) 7.20 (d,
Conclusion
We found that N,O-diaryl carbamate is spontaneously
transformed into symmetrical N,N′-diphenylurea in DMF in J=9.0Hz, 2H), 7.31 (m, 2H), 7.40–7.45 (m, 2H), 7.62 (d,
the presence of a catalytic amount of Et3N. This transforma- J=9.0Hz, 2H), 8.24 (d, J=9.0Hz, 2H).
tion requires a presence of aryl groups on the nitrogen and
Preparation of 3b Compound 3b was synthesized in
oxygen atoms of the carbamate. An electron-donating group a similar manner to that described for 3a, except that p-
on the aryl group inhibited the reaction. We could not obtain methoxyaniline was used in place of p-nitroaniline. It was

Vol. 66, No. 9 (2018)
Chem. Pharm. Bull.
883
purified by recrystallization from CH2Cl2 to afford colorless under reduced pressure. The crude product was recrystallized
1
needles (71%). H-NMR and mp were consistent with reported from ethanol to afford 3g as colorless needles (2.18g, 71%).
data.25)
1H-NMR and mp were consistent with reported data.29,30)
4-Methoxyphenyl N-(4-Methylphenyl)carbamate (3g)
mp 164.5–165.0°C; 1H-NMR (300MHz, CDCl3) 2.32 (s,
Phenyl N-(4-Methoxyphenyl)carbamate (3b)
mp 150.5–151.0°C; 1H-NMR (300MHz, CDCl3) 3.80 (s,
3H), 6.82 (brs, 1H), 6.88 (d, J=9.0Hz, 2H), 7.18–7.23 (m, 3H), 3H), 3.80 (s, 3H), 6.90 (d, J=9.0Hz, 2H), 7.08–7.14 (m, 4H),
7.35–7.42 (m, 4H).
7.32 (m, 2H).
Preparation of 3c A solution of phenyl chloroformate
Preparation of 3h Compound 3h was synthesized in a
(1.2mL, 9.5mmol) in CH2Cl2 (5mL) and tetrahydrofuran similar manner to that described for 1, except that aniline was
(THF) (5mL) was added to a solution of benzylamine used in place of p-toluidine. The product was purified by sil-
(1.0mL, 9.15mmol) and N,N-diisopropylethylamine (3.2mL, ica gel column chromatography (eluent, AcOEt–hexane=1:3),
18.3mmol) and in CH2Cl2 (10mL) and THF (10mL) in an then recrystallization from CH2Cl2 to afford 3h as colorless
1
ice bath. The mixture was stirred for 23h at r.t., and then prisms (19%). H-NMR and mp were consistent with reported
evaporated under reduced pressure. The crude product was data.23)
purified by silica gel column chromatography (eluent, AcOEt–
hexane=1:7) to afford 3c as a colorless solid (1.31g, 63%).
1H-NMR and mp were consistent with reported data.26)
Phenyl N-Benzylcarbamate (3c)
Phenyl N-Phenylcarbamate (3h)
mp 130.0–131.0°C; H-NMR (300MHz, CDCl3) 6.91 (brs,
1
1H), 7.11 (t, J=7.5Hz, 1H), 7.18–7.47 (m, 9H).
Compound Data Related to Table 2
N,N′-Bis(4-methoxyphenyl)urea (4)
mp 77.0–78.0°C; 1H-NMR (300MHz, CDCl3) 4.47 (d,
J=6.0Hz, 2H), 5.33 (brs, 1H), 7.14–7.23 (m, 3H), 7.28–7.41
(m, 7H).
1H-NMR was consistent with reported data31) 1H-NMR
;
(300MHz, DMSO-d6) 3.70 (s, 6H), 6.84 (d, J=8.1Hz, 4H),
Preparation of 3d Phenyl isocyanate (0.8mL, 7.3mmol) 7.32 (d, J=8.1Hz, 4H), 8.36 (brs, 2H).
was added to a solution of p-nitrophenol (1.00g, 7.2mmol)
in CH2Cl2 (20mL) in an ice bath. The reaction mixture was
N,N′-Bis(4-nitrophenyl)urea (6)
1H-NMR was consistent with reported data32) 1H-NMR
;
stirred for 19h at r.t., and then evaporated under reduced pres- (300MHz, DMSO-d6) 7.72 (d, J=9.1Hz, 4H), 8.22 (d,
sure. The crude product was purified by silica gel column J=9.1Hz, 4H), 9.65 (brs, 2H).
chromatography (eluent, CH2Cl2–hexane=5:1) to afford 3d as
N-Phenyl-N′-(4-methylphenyl)urea (8)
1
a colorless solid (0.569g, 31%). H-NMR and mp were consis-
1H-NMR was consistent with reported data33) 1H-NMR
;
tent with reported values.27)
(300MHz, DMSO-d6) 2.23 (s, 3H), 6.94 (t, J=7.4Hz, 1H), 7.07
(d, J=8.1Hz, 2H), 7.26 (t, J=8.1Hz, 2H), 7.32 (d, J=8.4Hz,
4-Nitrophenyl N-Phenylcarbamate (3d)
mp 146.0–147.0°C; 1H-NMR (300MHz, CDCl3) 6.91 2H), 7.43 (d, J=8.1Hz, 2H), 8.52 (brs, 1H), 8.59 (brs, 1H).
(brs, 1H), 7.16 (t, J=7.2Hz, 1H), 7.35–7.46 (m, 6H), 8.29 (d,
J=9.0Hz, 2H).
Preparation of 5 Synthesized for the purpose of com-
1
parison in the H-NMR experiment in Fig. 2a. A solution of
Preparation of 3e Compound 3e was synthesized in a p-anisidine (246mg, 2.0mmol) in Et2O (2mL) was added to
similar manner to that described for 3d, except that p-me- a solution of p-nitrophenyl isocyanate (328mg, 2.0mmol) in
thoxyphenol was used in place of p-nitrophenol. The product Et2O (5mL) in an ice bath. The mixture was stirred for 16h at
was purified by recrystallization from ethanol to afford a col- r.t., then the precipitate was collected by suction, and washed
orless solid (56%).
with Et2O. The crude product was recrystallized from metha-
nol to afford 5 as a colorless powder (134mg, 24%).
N-(4-Methoxyphenyl)-N′-(4-nitrophenyl)urea (5)
4-Methoxyphenyl N-Phenylcarbamate (3e)
mp 138.0–139.0°C; 1H-NMR (300MHz, CDCl3) 3.81 (s, 3H),
6.38–6.93 (m, 3H), 7.08–7.13 (m, 3H), 7.34 (t, J=7.5Hz, 2H),
1
mp 236.5–238.0°C; H-NMR (400MHz, DMSO-d6) 3.71 (s,
7.44 (d, J=7.5Hz, 2H); 13C-NMR(75MHz, CDCl3) 55.6, 114.4, 3H), 6.88 (d, J=9.2Hz, 2H), 7.37 (d, J=9.2Hz, 2H), 7.67 (d,
118.7, 122.5, 123.8, 129.1, 137.4, 144.1, 152.0, 157.2; IR (KBr) J=9.2Hz, 2H), 8.17 (d, J=8.1Hz, 2H), 8.73 (brs, 1H), 9.37
3344, 2924 2856, 1722, 1606, 1549, 1502, 1448, 1381, 1317, (brs, 1H); 13C-NMR (100MHz, DMSO-d6) 55.2, 114.0, 117.3,
1213, 1022, 904, 839, 758, 696, 663, 519cm−1; high resolution 120.5, 125.2, 131.9, 140.8, 146.6, 152.1, 154.9; IR (KBr) 2954,
(HR)-MS (electron ionization (EI)+) Calcd for C14H13NO3 (M+) 1691, 1645, 1614, 1593, 1552, 1506, 1468, 1406, 1342, 1304,
243.0890. Found 243.0889.
1228, 1167, 1109, 1032, 858, 761, 744, 688, 548cm−1; HR-MS
Preparation of 3f Phenyl isocyanate (2.7mL, 25mmol) (EI+) Calcd for C14H13N3O4 (M+) 287.0901. Found 287.0906.
1
was added to dry methanol (40mL) in a two-necked flask
Reaction Monitoring by H-NMR (Fig. 4) A mixture of
under Ar. The solution was stirred at 80°C for 30min, and 1 (42.6mg, 0.187mmol) and Et3N (2.6µL, 1.9µmol) in DMF-d7
evaporated under reduced pressure. The residue was cooled in (0.675mL) was heated in an NMR tube in an oil bath at 80°C.
1
a dry ice-acetone bath, affording a colorless solid 3f (3.67g, The H-NMR spectrum of the mixture was measured at the
1
98%). H-NMR and mp were consistent with reported data.28)
indicated times.
Methyl Phenylcarbamate (3f)
1
mp 43.0–44.0°C; H-NMR (300MHz, CDCl3) 3.78 (s, 3H),
Conflict of Interest The authors declare no conflict of
6.61 (brs, 1H), 7.07 (t, J=7.5Hz, 1H), 7.31 (t, J=7.5Hz, 2H), interest.
7.38 (t, J=7.5Hz, 2H).
Preparation of 3g Et3N (0.8mL, 5.7mmol) and p-tolyl
isocyanate (1.5mL, 12mmol) were added to a solution of p- article contains supplementary materials. Detail and H-NMR
Supplementary Materials The online version of this
1
1
methoxyphenol (1.50g, 12mmol) in toluene (57mL) at r.t. The spectrums of competitive reaction in Figs. 2 and 3; H- and
reaction mixture was stirred for 3h at r.t., and then evaporated 13C-NMR spectrums of compound 3e.

884
Chem. Pharm. Bull.
Vol. 66, No. 9 (2018)
17) Perveen S., Hai S. M. A., Khan R., Khan K. M., Afza N., Sarfaraz
T. B., Synth. Commun., 35, 1663–1674 (2005).
18) Wu X., Niu Q., Li T., Synth. Commun., 46, 1364–1369 (2016).
19) For a review of blocked isocyanates, see: Rolph M. S., Markowska
A. L. J., Warriner C. N., O’Reilly R. K., Polym. Chem., 7, 7351–
7364 (2016).
20) For an example of the transformation of a carbamate into a sym-
metrical urea, see: Lu Q.-W., Hoye T. R., Macosko C. W., J. Polym.
Sci. A Polym. Chem., 40, 2310–2327 (2002).
21) When the reaction was performed under Ar with strict anhydrous
condition, the reaction did not proceed to complete after 24h at this
condition, which implies a requirement of water for this reaction.
22) Thavonekham B., Synthesis, 1997, 1189–1194 (1997).
23) Lee H.-G., Kim M.-J., Park S.-E., Kim J.-J., Kim B. R., Lee S.-G.,
Yoon Y.-J., Synlett, 2009, 2809–2814 (2009).
References and Notes
1) Mok M. C., Kim S.-G., Armstrong D. J., Mok D. W., Proc. Natl.
Acad. Sci. U.S.A., 76, 3880–3884 (1979).
2) Wu J., Wang C., Leas D., Vargas M., White K. L., Shackleford D.
M., Chen G., Sanford A. G., Hemsley R. M., Davis P. H., Dong Y.,
Charman S. A., Keiser J., Vennerstrom J. L., Bioorg. Med. Chem.
Lett., 28, 244–248 (2018).
3) Cheung M., Tangirala R. S., Bethi S. R., Joshi H. V., Ariazi J. L.,
Tirunagaru V. G., Kumar S., ACS Med. Chem. Lett., 9, 103–108
(2018).
4) Wang C., Gao H., Dong J., Zhang Y., Su P., Shi Y., Zhang J.,
Bioorg. Med. Chem., 22, 277–284 (2014).
5) Wu S.-N., Peng H., Chen B.-S., Wang Y.-J., Wu P.-Y., Lin M.-W.,
Mol. Pharmacol., 74, 1696–1704 (2008).
6) Regan J., Pargellis C. A., Cirillo P. F., Gilmore T., Hickey E. R.,
Peet G. W., Proto A., Swinamer A., Moss N., Bioorg. Med. Chem.
Lett., 13, 3101–3104 (2003).
24) Li J., Guo X.-G., Wang L.-G., Ma X.-Y., Zhang Q.-H., Shi F., Deng
Y.-Q., Sci. China Chem., 53, 1534–1540 (2010).
25) Zhang L., Xia W., Wang B., Luo Y., Lu W., Synth. Commun., 41,
3140–3146 (2011).
7) Yamanaka M., J. Incl. Phenom. Macrocycl. Chem., 77, 33–48
(2013).
26) Diss M., Kennan A., Biopolymers, 86, 276–281 (2007).
27) Olma S., Ermert J., Coenen H. H., J. Labelled Comp. Radiopharm.,
49, 1037–1050 (2006).
8) Yamasaki R., Iida M., Ito A., Fukuda K., Tanatani A., Kagechika
H., Masu H., Okamoto I., Cryst. Growth Des., 17, 5858–5866
(2017).
28) AbdelHafez E. M. N., Aly O. M., Abuo-Rahma G. E.-D. A. A.,
King S. B., Adv. Synth. Catal., 356, 3456–3464 (2014).
29) Chong P. Y., Janicki S. Z., Petillo P. A., J. Org. Chem., 63, 8515–
8521 (1998).
30) Hutchby M., Houlden C. E., Ford J. G., Tyler S. N. G., Gagné M. R.,
Lloyd-Jones G. C., Booker-Milburn K. I., Angew. Chem. Int. Ed.,
48, 8721–8724 (2009).
9) For synthesis of ureas utilizing triphosgene as a phosgene surrogate,
see: Majer P., Randad R. S., J. Org. Chem., 59, 1937–1938 (1994).
10) Menger F. M., Glass L. E., J. Org. Chem., 39, 2469–2470 (1974).
11) Shawali A. S., Harhash A., Sidky M. M., Hassaneen H. M., Elkaabi
S. S., J. Org. Chem., 51, 3498–3501 (1986).
12) Koh H. J., Kim O. K., Lee H. W., Lee I., J. Phys. Org. Chem., 10,
725–730 (1997).
31) Mizuno T., Mihara M., Iwai T., Ito T., Ishino Y., Synlett, 2006,
2825–2830 (2006).
13) Spyropoulos C., Kokotos C. G., J. Org. Chem., 79, 4477–4483
(2014).
32) McGeary R. P., Bennett A. J., Tran Q. B., Prins J., Ross B. P., Tetra-
hedron, 65, 3990–3997 (2009).
33) Kotecki B. J., Fernando D. P., Haight A. R., Lukin K. A., Org. Lett.,
11, 947–950 (2009).
14) Kim H.-K., Lee A., Org. Biomol. Chem., 14, 7345–7353 (2016).
15) Ilieva S., Nalbantova D., Hadjieva B., Galabov B., J. Org. Chem.,
78, 6440–6449 (2013).
16) Hai S. M. A., Perveen S., Khan R. A., Khan K. M., Afza N., Nat.
Prod. Res., 17, 351–354 (2003).