Synthesis of Imidazolidin-2-ones and Imidazol-2-ones via Base-Catalyzed Intramolecular Hydroamidation of Propargylic Ureas under Ambient Conditions

Article abstract of DOI:10.1021/acs.joc.9b00064

The first organo-catalyzed synthesis of imidazolidin-2-ones and imidazol-2-ones via intramolecular hydroamidation of propargylic ureas is reported. The phosphazene base BEMP turned out to be the most active organo-catalyst compared with guanidine and amidine bases. Excellent chemo- and regioselectivities to five-membered cyclic ureas have been achieved under ambient conditions, with a wide substrate scope and exceptionally short reaction times (down to 1 min). A base-mediated isomerization step to an allenamide intermediate is the most feasible reaction pathway to give imidazol-2-ones, as suggested by DFT studies.

Full text of DOI:10.1021/acs.joc.9b00064

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Article
Synthesis of Imidazolidin-2-ones and Imidazol-2-ones
via Base-Catalyzed Intramolecular Hydroamidation
of Propargylic Ureas under Ambient Conditions
Alessandra Casnati, Antonio Perrone, Paolo Pio Mazzeo, Alessia Bacchi, Raffaella Mancuso, Bartolo
Gabriele, Raimondo Maggi, Giovanni Maestri, Elena Motti, András Stirling, and Nicola Della Ca'
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00064 • Publication Date (Web): 21 Feb 2019
Downloaded from http://pubs.acs.org on February 24, 2019
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The Journal of Organic Chemistry
Synthesis of Imidazolidin-2-ones and Imidazol-2-ones via Base-Catalyzed Intramolecular
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Hydroamidation of Propargylic Ureas under Ambient Conditions
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Alessandra Casnati,a Antonio Perrone,a Paolo P. Mazzeo,a,b Alessia Bacchi,a,b Raffaella Mancuso,c
Bartolo Gabriele,c Raimondo Maggi,a Giovanni Maestri,a Elena Motti,a András Stirlingd,* and Nicola
Della Ca’a,*
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a Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, 43124
Parma, Italy
b Biopharmanet-tec, Parco delle Scienze, 27/A, 43124 Parma, Italy
c Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, 87036 Arcavacata di
Rende, Cosenza, Italy
d Theoretical Chemistry Research Group, Institute of Organic Chemistry, Research Centre for Natural
Sciences, Budapest, Hungary
* Corresponding Author e-mail: stirling.andras@ttk.mta.hu; nicola.dellaca@unipr.it
Abstract: The first organo-catalyzed synthesis of imidazolidin-2-ones and imidazol-2-ones via
intramolecular hydroamidation of propargylic ureas is reported. The phosphazene base BEMP turned out
to be the most active organo-catalyst compared with guanidine and amidine bases. Excellent chemo- and
regioselectivities to 5-membered cyclic ureas have been achieved under ambient conditions, with wide
substrate scope and exceptionally short reaction times (down to 1 min). A base-mediated isomerization
step to an allenamide intermediate is the most feasible reaction pathway to give imidazol-2-ones, as
suggested by DFT studies.
Keywords: Organocatalysis, Hydroamidation, Ureas, Alkynes, Super bases, Imidazol-2-ones
Introduction
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Imidazol-2-ones and their analogues are omnipresent structural motifs of bioactive pharmaceutical
compounds and natural alkaloids (Figure 1).1 5-Membered cyclic ureas are also flexible key intermediates
in synthetic transformations2 and useful chiral auxiliaries in enantioselective syntheses.3
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9
O
Cl
N
O
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O
HN
NH
high activity against
enterovirus E71
SO2
N
HN
O
O
N
H2N
DW2282
5 N
N
SMe
anticancer agent
Enoximone
cardiovascular drug
O
O
Me
N
HN
N
NH
N
O
HN
Br
Br
CF3
HN
NH
H
O
H
O
3COOH
S
potent NK1
antagonist
CF3
Dibromophakellstatin
antineoplastic agent
Biotin
Figure 1. Selected bioactive 2-imidazol(idin)one derivatives.
The high value of these heterocycles for synthetic and pharmaceutical chemistry has driven continuous
efforts in the development of sustainable and more efficient protocols. Traditional synthetic routes to
imidazolidin-2-ones are mainly based on the carbonylation of diamines,4 which can require toxic
carbonylating agents, high-pressure facilities and harsh reaction conditions. Metal-catalyzed diamination
of olefins5 and aziridine ring expansion6 are elegant strategies; however, the widespread application suffer
from their inherent sophistication. The intramolecular hydroamidation approach7 offers a powerful, atom-
and step-economical alternative route to easily access richly decorated 5-membered cyclic ureas.4a,8,9 In
this context, propargylureas have been extensively investigated as readily available precursors for the
synthesis of both imidazolin-2-ones and imidazolidin-2-ones. The control of chemo- (O vs N cyclization)
and regio- (exo- vs endo-) selectivity in the cyclization step is generally addressed by means of transition
metal-catalysts.8a-h,10 As relevant example, Ag(I)-catalyzed one-pot protocol for the synthesis of 2-
imidazolones through cycloisomerization of an in situ formed propargylic urea was disclosed by Van der
Eycken in 2011.8d More recently, Reddy and coworkers have reported the synthesis of indole-fused cyclic
urea derivatives through an Ag-catalyzed sequence that involves an elegant double intramolecular
hydroamidation process.8b These interesting methods require however high catalyst loading (up to 30
mol%) and harsh reaction conditions. More sustainable metal-free protocols to efficiently access
imidazol-2-ones and imidazolidin-2-ones from propargylic ureas have been also developed by using
stoichiometric amount of bases or salts.9 For instance, Dethe and Lubell have recently proposed the use
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of NaOH9a and NaH9b for the synthesis of imidazole-2-thione and N‑amino-imidazolin-2-ones,
respectively, under mild conditions. Despite the usefulness of these methods, a base-catalyzed
intramolecular hydroamidation approach to imidazol-2-one derivatives is still of high demand and, to
date, totally unprecedented.
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Herein, we disclose the first base-catalyzed intramolecular hydroamidation of propargylic ureas
to highly substituted imidazolidin-2-ones and imidazol-2-ones. Notable features of our methodology
include (i) excellent chemo- and regio-selectivity to 5-membered cyclic ureas, (ii) wide substrate scope
and high functional group tolerance, (iii) very mild reaction conditions and (iv) remarkably short reaction
times. Further, thanks to key mechanistic insights on the reaction pathway, we demonstrated the feasibility
of a one-pot step-economical protocol starting from propargyl amines and isocyanates.
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Results and Discussion
Inspired by our recent studies on the base-catalyzed synthesis of imidazolidin-2-ones from
propargylamines, CO2 and primary amines,11 we started to investigate the intramolecular hydroamidation
reaction of propargylic ureas.12 Guanidine base TBD, widely exploited in a plethora of catalytic
transformations,13 including the abovementioned synthesis of imidazolidin-2-ones,11 was initially
employed as catalyst for the hydroamidation of propargylic urea 1a (Table 1) using similar reaction
conditions. We found that propargylic urea 1a in the presence of 10% of TBD at 100 °C in anhydrous
acetonitrile converted quantitatively to imidazolidinone 2a (Table 1, entry 1). Excellent results were also
achieved at lower temperatures (Table 1, entries 2 and 3) and, therefore, subsequent experiments were
tested at r.t. (22-23 °C). A series of similar organic bases were then evaluated (Table 1, entries 4-7).
MTBD and BTMG were found to be less effective, leading to imidazolidinone 2a in 82 and 67% yield
respectively, (Table 1, entry 4 and 5). On the contrary, DBU and TMG turned out to be totally inactive in
promoting the desired cyclization (Table 1, entries 6 and 7). Notably, the catalytic activity seemed to
follow the strength of the bases. We then resorted to 2-tert-butylimino-2-diethylamino-1,3-
dimethylperhydro-1,3,2-diazaphosphorine (BEMP), which is a stronger base that proved to be useful in
other hydroamination reactions.14 Gratifyingly, the use of 10 mol% of BEMP afforded 2a in quantitative
yield (Table 1, entry 8). Furthermore, the reaction time decreased dramatically to 30 minutes. This
significant improvement let us to decrease the amount of catalyst down to 1 mol%, still keeping a high
reaction performance (Table 1, entries 9 and 10). Other solvents were then tested (Table 1, entries 11-13)
and we found that MeCN was crucial to trigger an efficient reaction. Notably, the presence of water in the
mixture, detrimental for other protocols,8d,9b did not affect the final outcome (Table 1, entry 14). Finally,
no reaction took place in the control experiment in the absence of catalyst (Table 1, entry 15).
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Table 1. Optimization studya
O
O
base
Ph
HN
NPh
N
H
N
solvent, T, time
H
1a
2a
8
Yield (%)b
9
Entry
Base
Solvent
T
Tim
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(mol %)
(°C) e
2a
(h)
24
24
24
24
24
24
24
0.5
1
1
TBD (10)
TBD (10)
TBD (10)
MTBD (10)
BTMG (10)
DBU (10)
TMG (10)
BEMP (10)
BEMP (5)
BEMP (1)
BEMP (5)
BEMP (5)
BEMP (5)
BEMP (5)
-
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
EtOAc
THF
100
50
99
99
99
82
67
-
2
3
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
4
5
6
7
-
8
99
99
93
-
9
10
11
12
13
14
15
7
24
24
24
1
-
MeOH
MeCNc
MeCN
-
99
-
24
N
N
N
N
N
N
N
N
H
DBU
pKad 23.90
TBD
pKad 26.03
MTBD
pKad 25.43
t-Bu
tBu
NH
N
N
N
P N
N
N
N
N
N
TMG
pKad 23.30
BTMG
pKa n.d.e
BEMP
pKad 27.58
a Reaction conditions: 1a (0.4 mmol), base (1-10 mol%), solvent (4 mL). b Yields of 2a were determined
via 1H NMR analysis using methylbenzoate as internal standard. c 0.4 mmol (1 equiv) of H2O were added.
d pKa is referred to its conjugate acid in MeCN.13 e Not determined.14
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To illustrate the scope of this methodology, a series of propargyl ureas bearing a quaternary carbon α to
the triple bond were then prepared. Under optimal conditions (Table 1, entry 9), propargylic ureas 1a-l
reacted smoothly to give the corresponding imidazolidin-2-ones 2a-l in excellent yields (Table 2).
Reactions reached completion within 1 to 16 hours at r.t.. Both electron-donating (Me) and electron-
withdrawing (F, CO2Me) groups on the aryl substituent were well tolerated in this simple and robust
methodology (2b-d, 82-98%). The reaction rate is slower increasing the hindrance on the carbon α to the
triple bond (2e and 2f, 3 and 16 hours). However, the presence of a substituent on the nitrogen β to the
triple bond caused a lower yield of the corresponding cyclic urea, as shown in the case of 2g (R3 = Bn,
52%). Propargylic ureas bearing an internal triple bond led to the corresponding imidazolidin-2-ones in
high yield (2h-l, 83-97%). Aryl and alkyl groups on the triple bond were well tolerated. In all cases, the
Z product was the preferred one,15 although the stereocontrol was not complete. Ureas bearing alkyl
substituent in R4, such as n-Bu, were unreactive under these optimized conditions. Interestingly, urea 1m
that bears an ester group in suitable position (R4 = CH2CO2Et) led to hydantoin 2m’ (72%),9c leaving the
triple bond untouched.
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Table 2. Scope of the BEMP-catalyzed synthesis of imidazolidin-2-ones 2a,b
O
O
R2
R2
N
R3
R4
R3
R4
5% BEMP
N
N
N
H
R1
CH3CN, r.t.
R2
R1
R2
1
2
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O
O
2a
1
2
H
H
N
N
N
N
3
4
5
6
7
2e
, 99%, 3h
O
2a
, 97%, 1h
O
R5
(R5 = Me), 82%, 16h
(R5 = F), 97%, 1.5h
2bc
2c
H
H
N
N
N
N
(R5 = CO2Me), 98%, 6h
2d
8
9
2f
, 95%, 16h
N
O
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12
13
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O
O
Bn
N
N
Bn
N
N
H
N
7
2h
, 83%, 16h
Z/E 1:0.06
2g
, 52%, 16h
2i
, 87%, 16h, Z/E 1:0.25
2i
O
O
Z
H
H
N
N
N
N
S
R6
2l
, 97%, 1.5h
Z/E 1:0.8
(R6 = CF3), 93%, 4h, Z/E 1:0.3
2j
(R6 = OMe), 84%, 16h, Z/E 1:0.04
2k
F
O
2n'
N
N
NH
H
N
S
O
2m'
2n'd
, 72%, 50 °C, 16h
, 98, 3h
a Reaction conditions: 1 (0.4 mmol), BEMP (5 mol%), MeCN (4 mL), room temperature. b Yields of 2. c
The reaction was performed at 40 °C. d Compound 2n’ was obtained directly from propargylic amine and
isothiocyanate without catalyst (see SI for details).
We also tested the reactivity of a propargylic thiourea, which is reported to give imidazole-2-thiones under
basic conditions.9a On the contrary, thiazolidin-2-imine 2n’ was selectively obtained directly from
propargylic amine and isothiocyanate precursors through intramolecular S-cyclization without catalyst.
The structure of 2n’ was undoubtedly confirmed by SC-XRD (see the SI for details).15
We then further explored the substrate scope of the transformation by employing a variety of
propargylic ureas 3 bearing a tertiary carbon α to the triple bond (Table 3). In this case, selective formation
of imidazol-2-ones 4 was observed, with formal double bond shift from the exo- to the endocyclic
position. To our delight, reaction times were impressively shortened. Upon reagent mixing, the reaction
completes in about one minute. The protocol was again characterized by a remarkable tolerance of
valuable functional groups, including Cl (4i, 86%), Br (4k, 68%), F (4f, 93%), OMe (4h, 77%) or vinyl
(4j,15 75%) substituents. It is worth noting that this ample tolerance ensures vast handles for further
functionalizations. Alkyl substituents on the triple bond (R1) or on terminal nitrogen (R4) gave low yields,
as shown for example for 4b and 4l (18% and 33% yield, respectively). Alkyl or benzyl substituents on
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nitrogen β to the triple bond (R3) led to excellent yield of product 4, even for more sterically demanding
groups, as in the case of 4d (93% yield). This is complementary to the trend observed with products 2
(2g, Table 2). Electronic effects exerted by substituents in para position on the aromatic ring (R1) were
also explored. Urea 3n bearing a tolyl group on the triple bond (R1 = 4-MeC6H4) led to the corresponding
imidazolone 4n in 81% yield, which is slightly less than those observed for 4a (R1 = C6H5). The best
results were obtained with electron withdrawing groups, such as Cl (4o, 98%) and F (4p, 97%). Finally,
the unsubstituted propargylic urea 3q (R1, R2, R3 = H) did not provide the corresponding imidazolone 4q,
being unreactive under these conditions.
1
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Table 3. Scope of the BEMP-catalyzed synthesis of imidazol-2-ones 4a,b
O
O
R2
H
R4
R3
R4
5% BEMP
N
N
N
R3
N
H
R1
CH3CN, r.t.
1 min
R1
R2
3
4
O
O
O
Ph
Ph
Ph
N
N
N
N
N
N
Ph
Ph
, 71%
8
4a
4b
, 83%
, 18%
4c
O
O
4c
Ph
Ph
N
N
N
N
Ph
Ph
, 93%
R5
4d
(R5 = Me), 91%
(R5 = F), 93%
4e
4f
O
Ph
O
4j
N
N
Ph
Ph
N
N
Ph
Ph
Ph
R7
R6
4g
(R6 = Me), 84%
(R6 = OMe), 77%
(R7 = Cl), 86%
(R7 = CH=CH2), 75%
4i
4j
4h
O
O
O
Ph
N
N
N
N
N
N
Ph
Br
Ph
Ph
4k
, 68%
4m
4l
, 84%
, 33%
O
O
Ph
(R8 = Me), 81%
(R8 = Cl), 98%
(R8 = F), 97%
Ph
N
N
4n
HN
N
4o
4p
R8
4q
, -
a Reaction conditions: 3 (0.4 mmol), BEMP (5 mol%), MeCN (4 mL), room temperature, 1 min. b Yields
of 4.
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To further demonstrate the applicability of this protocol, the one-pot synthesis of imidazol-2-one
derivatives starting from propargylic amines and isocyanates was performed under standard conditions.
Gratifyingly, compound 2a was quantitatively obtained in 1 hour from 2-methylbut-3-yn-2-amine and
phenyl isocyanate (Scheme 1a). Without further optimization, imidazolinone 4a was synthesized directly
from the propargylamine 3a and phenyl isocyanate in 62% yield, using 10 mol% of BEMP (Scheme 1b).
Noteworthy, this intermolecular reaction was still complete within one minute.
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Scheme 1. Representative examples of the one-pot synthesis of imidazolidinin-2-one 2a and imidazolin-
2-one 4a from propargylic amines and isocyanates.
O
5% BEMP
Ph
NH2
a)
+
OCN Ph
HN
2a
N
CH3CN, r.t.
1h
, quant.
O
Ph
H
NH
Bn
BEMP
b)
Bn
Ph
N
N
+
OCN Ph
Ph
CH3CN, r.t.
Ph
Ph
1 min
4a
4a
, 51%
5% BEMP
, 62%
10% BEMP
Intrigued by the complete chemo- and site selectivity features as well as by the unexpectedly fast
formation of imidazol-2-ones 4 under very mild conditions, we carried out computational studies to gain
insights into the reaction mechanism. Investigation begun employing the Gaussian09 package16 using the
range separated, hybrid b97xd functional.17 The possible reaction routes have been studied in terms of
solvent-corrected Gibbs free energy values (see SI for details). Figure 2 shows the most feasible
mechanism to generate imidazolidinin-2-one 2a from propargylic urea 1a. The reaction starts with the
abstraction of the most acidic urea proton by the base, which is a slightly endergonic process. We obtained
good correlation between the pKa of the bases and the energonicity of the deprotonation step.18 The levels
obtained with the strongest base (BEMP) are shown in blue. The deprotonation yields 1a-D-BEMPH+
(ΔG +5.5 kcal/mol). We observed that upon this proton transfer, the conjugated acid/base pair dissociates
as higher ΔG values were obtained modelling a tight ion pair. We explained this by the entropy penalty
of the association of the two ions,19 and also by the enhanced solvation of the two independent ions which
together boost therefore dissociation in the polar MeCN solvent. The deprotonated urea can then react
with the triple bond in 4 different ways depending on the cyclization fashion. N- or O-carbon bond
formation via either 5-exo- or 6-endo-dig cyclization modes. The formation of the anionic form of product
2a (2a-D-N5) is the most favorable pathway both kinetically and thermodynamically (not shown here,
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see SI, Figure S1). Eventually, the cyclization is followed by the strongly exergonic protonation yielding
the product 2a (ΔG -36.7 kcal/mol). The rate determining step is the cyclization, which requires a
moderate 20.8 kcal/mol activation free energy (from 1a to TS-N5) in the presence of BEMP. This is fully
compatible with the observed reaction rate.20 The calculated trend among different bases evenly correlates
with the experimental results listed in Table 1. Indeed, stronger bases proved to be better catalysts as they
can more easily deprotonate the substrate (Figure 2).
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Figure 2. Gibbs free energy profile of the formation of imidazolidin-2-one 2a (N-5-exo-dig cyclization
pathway). Color code used for the effect of bases: blue: BEMP as base; green, from top to bottom: TMG,
DBU, TBD, MTBD, BTMG as base.21
Secondly, formation of imidazol-2-one 4a from 3a was investigated. The initial base-catalyzed
isomerization of the triple bond to the corresponding allenamide was the most favored pathways to
imidazol-2-ones 4a (Figure 3, blue pathway). The proton of 3a highlighted in red became the most acidic
one. This ensures that the initial allenamide formation is preferred to urea deprotonation (Figure 3, green
pathway). Hence, the resting state under the reaction conditions is allenamide I1. Isomerization of the
propargylic arm to the corresponding allenamide is highly plausible under strongly basic conditions.22
Then, the N-H deprotonation can occur and leads to the formation of the imidazol-2-one ring (4a-D-1)
through a low barrier transition state. The final protonation yields the neutral product in a highly exergonic
step. The calculations confirmed that the central carbon of the allene moiety is the most electron-
deficient,23 which explains the preference for the 5-membered ring formation. The barrier for the
cyclization step is only 12.5 kcal/mol (from I1 to TS3-4). This suggests a very fast reaction, in perfect
agreement with the experimental observations.24
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Figure 3. Gibbs free energy profile of the formation of imidazol-2-one 4a, employing BEMP as catalyst.
Blue profile: allene-route; green profile: mechanism analogue to the one presented in Fig. 2.
Conclusion
In summary, we have developed the first organo-catalyzed method to access imidazolidin-2-ones
and imidazol-2-ones from propargylureas under ambient conditions. The protocol is simple, tolerates the
presence of water and provides 5-membered cyclic ureas with excellent space-time yields. DFT
calculations provided support for the non-assisted cyclization of deprotonated urea in the imidazolidin-2-
one formation, and revealed the involvement of an allene intermediate in the imidazol-2-one pathway.
The one-pot protocol starting from propargylic amines and isocyanates was also demonstrated. We
anticipate that unique features of this method will ensure wide interest and vast application within the
chemistry community at large.
Experimental Section
General Methods
All chemicals were purchased from commercial sources and used as received, unless otherwise noted.
Solvents were dried and stored over molecular sieves previously activated in an oven (450 °C overnight).
Organocatalyzed reactions were carried out under nitrogen using standard Schlenk technique. Reactions
were analyzed by thin layer chromatography (TLC) on silica gel 60 F254. GC analyses were performed
with an Agilent Tenchnologies 7820A equipped with a FID detector and a 30 m capillary column. GC-
MS analyses (m/z, relative intensity %) were performed with an Agilent Technologies 6890N gas
chromatograph coupled to an 5973N mass selective detector (Agilent Technologies) working at 70 eV
ionizing voltage. Column chromatography was performed on silica gel 60 (70–230 mesh). 1H, 13C and 19F
NMR spectra were recorded at 300 K on Bruker Avance 400 or 300 MHz using the solvent as internal
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standard (7.26 ppm for 1H NMR and 77.00 ppm for 13C NMR for CDCl3). The terms m, s, d, t, q and quint
represent multiplet, singlet, doublet, triplet, quadruplet and quintuplet respectively, and the term br means
a broad signal. Exact masses were recorded on a LTQ ORBITRAP XL Thermo Mass Spectrometer (ESI
source). Melting points were measured with an Electrothermal apparatus and are uncorrected.
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Experimental procedures
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Synthesis of propargylic ureas 1a-f, 1m, 3q25
A dry round bottom 2-necked flask, containing a magnetic stir bar, was charged with the selected
isocyanate (2.5 mmol), the desired propargylic amine (2.5 mmol) and dry THF (25 mL). The resulting
mixture was stirred at room temperature for 1 h. The solvent was removed under reduced pressure. Yields
were quantitative and propargylic ureas 1a-f, 1m and 3q were employed without further purification.
Synthesis of propargylic ureas 1i-l through Sonogashira coupling26
A Schlenk type flask equipped with a magnetic stir bar, was charged with Pd(PPh3)2Cl2 (0.02 mmol, 2
mol%, 14 mg), CuI (0.07 mmol, 7 mol%, 13 mg) and Et3N (5 mL) under inert atmosphere (N2). The aryl
iodide (1 mmol, 1 equiv) and the propargylic urea (1.2 equiv) were dissolved in dry CH2Cl2 (7 mL) and
then added. The reaction mixture was stirred at room temperature overnight. The crude mixture was
filtered through a fritted funnel, the solid residue washed with CH2Cl2, and the combined organic solutions
were concentrated under reduced pressure. Purification via flash column chromatography yielded the
desired propargyl urea.
Synthesis of propargylic urea 1g27
A solution of 2-methylbut-3-yn-2-amine (5 mmol, 519 μL) and benzaldehyde (5 mmol, 507 μL) in MeOH
(10 mL) was stirred at room temperature overnight. Sodium borohydride (10 mmol, 378 mg) was then
added to the reaction mixture at 0 °C for 1 hour under stirring. Then the reaction crude was diluted with
water (25 mL) and extracted with CH2Cl2 (3 x 40 mL). The organic layers were combined, dried over
MgSO4, filtered and concentrated under reduced pressure. The crude reaction mixture was purified by
silica gel column chromatography (Eluent: hexane:ethyl acetate 7:3) to afford N-benzyl-2-methylbut-3-
yn-2-amine in 55% yield (476 mg).
A dry round bottom 2-necked flask, containing a magnetic stir bar, was charged with phenyl isocyanate
(2.5 mmol, 297 mg), N-benzyl-2-methylbut-3-yn-2-amine (2.5 mmol, 432 mg) and dry THF (25 mL).25
The resulting mixture was stirred at room temperature for 1h. The solvent was removed under reduced
pressure. The yield is quantitative and propargylic urea 1g was employed without further purification.
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Synthesis of N-Benzyl-2-methyldodec-3-yn-2-amine28
A test tube equipped with a magnetic stirrer was charged with CuI (0.6 mmol, 30% mol, 114 mg). The
test tube was sealed and flushed with N2 and then was charged with dec-1-yne (2 mmol, 361 μL), acetone
(2 mmol, 147 μL) and benzylamine (2 mmol, 219 μL). The test tube was then placed in an oil bath at 75
°C and it was allowed to stir overnight. The crude was purified by flash column chromatography using
hexane/ethyl acetate (9:1) as eluent to give the desired amine (206 mg, 31% yield) as transparent oil.
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Synthesis of α-mono substituted propargylic amines28
In a typical experiment, CuI (0.6 mmol, 30% mol, 114 mg) was charged in a test tube equipped with a
magnetic stirrer. The test tube was sealed and flushed with N2 and then was charged with the alkyne (2
mmol), the aldehyde (2 mmol), and the amine (2 mmol). The test tube was then placed in an oil bath at
75 °C and it was allowed to stir overnight. The crude reaction mixture was purified by silica gel column
chromatography with a mixture of hexane/ethyl acetate (from 95:5 to 80:20) to provide the desired
secondary propargylic amine.
Synthesis of propargylic ureas 1h and 3a-p25
A dry round bottom 2-necked flask, containing a magnetic stir bar, was charged with the selected
isocyanate (1 mmol), the desired propargylic amine (1 mmol) and dry THF (10 mL). The resulting mixture
was stirred at room temperature for 1 h. The solvent was removed under reduced pressure. Yields were
quantitative for propargylic ureas 3a-k, 3n-p, that were employed without further purification. Silica gel
column chromatography (Eluent: hexane/ethyl acetate) was required to isolate propargylic ureas 3l and
3m with 45 and 62% yield, respectively.
General procedure for the BEMP-catalyzed synthesis of imidazolidin-2-ones 2 (Table 2)
A test tube, equipped with a magnetic stir bar, was charged with propargylic urea 1 (0.4 mmol) and
CH3CN (4 mL). BEMP (5 mol%, 6μL) was added. The reaction mixture was stirred at room temperature
and monitored by TLC. After completion, the solvent was removed under reduced pressure. The crude
was purified by silica gel column chromatography with a mixture hexane/ethyl acetate.
General procedure for the BEMP-catalyzed synthesis of imidazol-2-ones 4 (Table 3)
A test tube, equipped with a magnetic stir bar, was charged with propargylic urea 3 (0.4 mmol) and
CH3CN (4 mL). BEMP (5 mol%, 6μL) was added. The reaction mixture was stirred at room temperature
for 1 min (TLC confirmed the completion of the reaction). The solvent was removed under reduced
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pressure. The crude was purified by silica gel column chromatography with a mixture hexane/ethyl
acetate.
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One-pot BEMP-catalyzed synthesis of 2a from propargylic amine and isocyanate (Scheme 1a)
A test tube, equipped with a magnetic stir bar, was charged with 2-methylbut-3-yn-2-amine (0.4 mmol,
33 mg), phenyl isocyanate (0.4 mmol, 48 mg) and CH3CN (4 mL). BEMP (5 mol%, 6μL) was added. The
reaction mixture was stirred at room temperature and monitored by TLC. After completion (1h), the
solvent was removed under reduced pressure. The crude was purified by silica gel column
chromatography (Eluent: hexane:ethyl acetate 1:1) to afford 2a in quantitative yield (81 mg).
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One-pot BEMP-catalyzed synthesis of 4a from propargylic amine and isocyanate (Scheme 1b)
A test tube, equipped with a magnetic stir bar, was charged with N-benzyl-1,3-diphenylprop-2-yn-1-
amine (0.4 mmol, 119 mg), phenyl isocyanate (0.4 mmol, 48 mg) and CH3CN (4 mL). BEMP (5 mol%,
6μL) was added. The reaction mixture was stirred at room temperature for 1 min. Solvent was removed
under reduced pressure. The crude was purified by silica gel column chromatography (Eluent:
hexane:ethyl acetate 6:4) to afford 4a in 51% yield (85 mg). With 10% of BEMP, 4a was isolated in 62%
yield (103 mg).
Synthesis of 2n’25
A dry 2-necked flask containing a magnetic stir bar was charged with 1-fluoro-4-isothiocyanatobenzene
(1 mmol, 122 μL), 2-methylbut-3-yn-2-amine (1 mmol, 105 μL) and dry THF (10 mL). The resulting
mixture was stirred at room temperature and monitored by TLC. After 3 hours, the solvent was removed
under reduced pressure. The crude did not require purification and product 2n’ was recovered in 98%
yield (231 mg) as yellow solid.
N-Benzyl-2-methyldodec-3-yn-2-amine
N-Benzyl-2-methyldodec-3-yn-2-amine was synthesized from 2 mmol of starting materials, according to
the general procedure.28 The crude was purified by flash column chromatography using hexane/ethyl
1
acetate (9:1) as eluent to give the desired amine (206 mg, 31% yield) as transparent oil. H NMR (400
MHz, CDCl3) δ 7.40–7.35 (m, 2H), 7.34–7.30 (m, 2H), 7.25–7.22 (m, 1H), 3.88 (s, 2H), 2.23 (t, J = 7.0
Hz, 2H), 1.59–1.49 (m, 2H), 1.47–1.42 (m, 2H), 1.40 (s, 6H), 1.34–1.27 (m, 9H), 0.90 (t, J = 6.8 Hz, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ 141.2, 128.6, 128.5, 126.9, 85.3, 82.4, 50.3, 49.2, 32.0, 30.1, 29.4,
29.2 (2C), 29.0, 22.8, 18.8, 14.2. HRMS (ESI) calcd for C20H32N (M+H)+ m/z 286.2535, found m/z
286,2533.
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N-Benzyl-2-methylbut-3-yn-2-amine
N-Benzyl-2-methylbut-3-yn-2-amine was synthesized according to the general procedure.27 The crude
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desired amine (476 mg, 55% yield) as white solid; m.p. (hexane) 44.7–45.3 °C. H NMR (300 MHz,
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CDCl3) δ 7.43–7.33 (m, 4H), 7.31–7.26 (m, 1H), 3.91 (s, 2H), 2.39 (s, 1H), 1.46 (two overlapping signals:
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brs and s, 7H). Spectroscopic data were consistent with literature values.29
N-Benzyl-1,3-diphenylprop-2-yn-1-amine
N-Benzyl-1,3-diphenylprop-2-yn-1-amine was synthesized according to the general procedure.28 The
crude was purified by flash column chromatography using hexane/ethyl acetate (8:2) as eluent to give the
desired amine (349 mg, 59% yield) as viscous colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J =
7.4 Hz, 2H), 7.59–7.55 (m, 2H), 7.50–7.41 (m, 5H), 7.40–7.36 (m, 5H), 7.35–7.31 (m, 1H), 4.88 (s, 1H),
4.12–4.00 (m, 2H), 2.01 (bs, 1H). Spectroscopic data were consistent with literature values.30
N-Benzyl-1-phenylundec-2-yn-1-amine
N-Benzyl-1-phenylundec-2-yn-1-amine was synthesized according to the general procedure.28 The crude
was purified by flash column chromatography using hexane/ethyl acetate (9:1) as eluent to give the
desired amine (342 mg, 53% yield) as yellowish oil. 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 7.4 Hz,
2H), 7.48–7.41 (m, 4H), 7.40–7.37 (m, 2H), 7.36–7.29 (m, 2H), 4.65 (s, 1H), 4.04–3.94 (m, 2H), 2.37
(further split t, J = 7.0 Hz, 2H), 1.79 (bs, 1H), 1.70–1.60 (m, 2H), 1.57–1.48 (m, 2H), 1.44–1.34 (m, 8H),
0.98 (t, J = 6.9 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 141.1, 140.1, 128.5, 128.4, 128.2, 127.7,
127.5, 127.0, 86.1, 79.9, 53.3, 51.1, 31.9, 29.3, 29.2, 29.0, 28.9, 22.8, 18.9, 14.2. HRMS (ESI) calcd for
C24H32N (M+H)+ m/z 334.2534, found m/z 334.2530.
N-(1,3-Diphenylprop-2-yn-1-yl)butan-1-amine
N-Benzyl-1,3-diphenylprop-2-yn-1-amine was synthesized according to the general procedure.28 The
crude was purified by flash column chromatography using hexane/ethyl acetate (8:2) as eluent to give the
desired amine (315 mg, 60% yield) as viscous yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.68 (d, J = 7.2
Hz, 2H), 7.62–7.50 (m, 2H), 7.49–7.40 (m, 2H), 7.39–7.32 (m, 4H), 4.88 (s, 1H), 2.98–2.88 (m, 1H),
2.86–2.70 (m, 1H), 1.64–1.38 (m, 4H), 1.00 (t, J = 7.3 Hz, 3H). Spectroscopic data were consistent with
literature values.31
1,3-Diphenyl-N-(1-phenylethyl)prop-2-yn-1-amine
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1,3-Diphenyl-N-(1-phenylethyl)prop-2-yn-1-amine was synthesized according to the general procedure.28
The crude was purified by flash column chromatography using hexane/ethyl acetate (9:1) as eluent to give
the desired amine (257 mg, 42% yield) together with the corresponding imine intermediate.32 1H NMR
(400 MHz, CDCl3) δ 7.62−7.31 (m, 30H), 4.71 (s, 1H), 4.50 (s, 1H), 4.40 (q, J = 6.6 Hz, 1H), 3.96 (q, J
= 6.6 Hz, 1H), 1.76 (brs, 2H), 1.45 (d, J = 6.6 Hz, 3H), 1.42 (d, J = 6.6 Hz, 3H). Spectroscopic data were
consistent with literature values.32
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N-(4-Methylbenzyl)-1,3-diphenylprop-2-yn-1-amine
N-(4-Methylbenzyl)-1,3-diphenylprop-2-yn-1-amine was synthesized according to the general
procedure.28 The crude was purified by flash column chromatography using hexane/ethyl acetate (9:1) as
eluent to give the desired amine (433 mg, 70% yield) as viscous yellow oil. 1H NMR (400 MHz, CDCl3)
δ 7.78 (d, J = 7.2 Hz, 2H), 7.69–7.66 (m, 2H), 7.53 (t, J = 7.4 Hz, 2H), 7.49–7.44 (m, 6H), 7.30 (d, J =
7.8 Hz, 2H), 4.96 (s, 1H), 4.12 (s, 2H), 2.49 (s, 3H), 1.98 (bs, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ
140.4, 136.8, 136.6, 131.8, 129.1, 128.5, 128.4, 128.3, 128.2, 127.8, 127.7, 123.2, 89.4, 85.7, 53.6, 50.9,
21.2. HRMS (ESI) calcd for C23H22N (M+H)+ m/z 312.1752, found m/z 312.1754.
N-(4-Fluorobenzyl)-1,3-diphenylprop-2-yn-1-amine
N-(4-Fluorobenzyl)-1,3-diphenylprop-2-yn-1-amine was synthesized according to the general
procedure.28 The crude was purified by flash column chromatography using hexane/ethyl acetate (9:1) as
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eluent to give the desired amine (490 mg, 78% yield) as viscous yellowish oil. H NMR (400 MHz,
CDCl3) δ 7.73–7.68 (m, 2H), 7.62–7.57 (m, 2H), 7.49–7.42 (m, 4H), 7.42–7.36 (m, 4H), 7.13–7.07 (m,
2H), 4.87 (s, 1H), 4.04 (s, 2H), 1.89 (bs, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 162.1 (d, JC,F = 244.8
Hz), 135.6 (d, JC,F = 3.1 Hz), 140.3, 131.8, 130.0 (d, JC,F = 7.9 Hz), 128.6, 128.4, 128.3, 127.9, 127.7,
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123.1, 115.2 (d, JC,F = 21.2 Hz), 89.2, 85.9, 53.6, 50.4. F{1H} NMR (376 MHz, CDCl3) δ -115.56.
HRMS (ESI) calcd for C22H18FN (M+H)+ m/z 316.1501, found m/z 316.1498.
N-Benzyl-3-phenyl-1-(p-tolyl)prop-2-yn-1-amine
N-Benzyl-3-phenyl-1-(p-tolyl)prop-2-yn-1-amine was synthesized according to the general procedure.28
The crude was purified by flash column chromatography using hexane/ethyl acetate (9:1) as eluent to give
the desired amine (533 mg, 86% yield) as viscous colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.69–7.65
(m, 2H), 7.61–7.56 (m, 4H), 7.53–7.40 (m, 7H), 7.27 (d, J = 7.8 Hz, 1H), 4.94 (s, 1H), 4.21–4.12 (m, 2H),
2.53 (s, 3H), 2.11 (bs, 1H). Spectroscopic data were consistent with literature values.33
N-Benzyl-1-(4-methoxyphenyl)-3-phenylprop-2-yn-1-amine
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N-Benzyl-1-(4-methoxyphenyl)-3-phenylprop-2-yn-1-amine was synthesized according to the general
procedure.28 The crude was purified by flash column chromatography using hexane/ethyl acetate (8:2) as
eluent to give the desired amine (376 mg, 58% yield) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.68–
7.59 (m, 4H), 7.54–7.49 (m, 2H), 7.46–7.39 (m, 5H), 7.38–7.33 (m, 1H), 7.04–6.98 (m, 2H), 4.88 (s, 1H),
4.12–4.03 (m, 2H), 3.88 (s, 3H), 1.94 (bs, 1H). Spectroscopic data were consistent with literature values.30
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N-Benzyl-1-(3-chlorophenyl)-3-phenylprop-2-yn-1-amine
N-Benzyl-1-(3-chlorophenyl)-3-phenylprop-2-yn-1-amine was synthesized according to the general
procedure.28 The crude was purified by flash column chromatography using hexane/ethyl acetate (9:1) as
eluent to give the desired amine (342 mg, 52% yield) as dark yellow oil. 1H NMR (300 MHz, CDCl3) δ
7.75–7.72 (m, 1H), 7.63–7.58 (m, 3H), 7.53–7.48 (m, 2H), 7.47–7.40 (m, 5H), 7.39–7.34 (m, 3H), 4.87
(s, 1H), 4.07 (s, 2H), 2.03 (bs, 1H). 13C{1H} NMR (75 MHz, CDCl3) δ 142.4, 139.6, 134.4, 131.8, 129.8,
128.6, 128.5, 128.4 (2C), 128.0, 127.9, 127.2, 125.9, 122.9, 88.5, 86.3, 53.2, 51.1. HRMS (ESI) calcd for
C22H18ClN (M+H)+ m/z 332.1206, found m/z 332.1203.
N-Benzyl-3-phenyl-1-(3-vinylphenyl)prop-2-yn-1-amine
N-Benzyl-3-phenyl-1-(3-vinylphenyl)prop-2-yn-1-amine was synthesized according to the general
procedure.28 The crude was purified by flash column chromatography using hexane/ethyl acetate (9:1) as
eluent to give the desired amine (504 mg, 78% yield) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.83
(s, 1H), 7.71–7.63 (m, 3H), 7.57 (d, J = 7.1 Hz, 2H), 7.53–7.39 (m, 8H), 6.90 (dd, J = 17.6, 10.9 Hz, 1H),
5.94 (d, J = 17.6, 1H), 5.42 (d, J = 10.9 Hz, 1H), 4.97 (s, 1H), 4.19–4.11 (m, 2H), 2.11 (bs, 1H). 13C{1H}
NMR (101 MHz, CDCl3) δ 140.6, 139.8, 137.8, 136.8, 131.8, 128.7, 128.4 (2C), 128.3, 128.2, 127.2,
127.1, 125.7, 125.6, 123.1, 114.1, 89.2, 85.8, 53.6, 51.1. HRMS (ESI) calcd for C24H22N (M+H)+ m/z
324.1752, found m/z 324.1755.
N-Benzyl-1-(2-bromophenyl)-3-phenylprop-2-yn-1-amine
N-Benzyl-1-(2-bromophenyl)-3-phenylprop-2-yn-1-amine was synthesized according to the general
procedure.28 The crude was purified by flash column chromatography using hexane/ethyl acetate (9:1) as
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eluent to give the desired amine (558 mg, 74% yield) as viscous pale orange oil. H NMR (400 MHz,
CDCl3) δ 7.92 (dd, J = 7.7, 1.7 Hz, 1H), 7.64 (dd, J = 8.0, 1.2 Hz, 1H), 7.61–7.56 (m, 2H), 7.50 (d, J =
6.9 Hz, 2H), 7.42–7.37 (m, 6H), 7.36–7.31 (m, 1H), 7.24–7.19 (m, 1H), 5.28 (s, 1H), 4.12–4.02 (m, 2H),
2.03 (bs, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 139.5, 139.4, 133.2, 131.8, 129.6, 129.4, 128.7, 128.4,
128.3 (2C), 127.8, 127.2, 123.8, 123.0, 88.4, 85.8, 53.7, 51.7. HRMS (ESI) calcd for C22H19BrN (M+H)+
m/z 376.0700, found m/z 376.0703.
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N-Benzyl-1-phenyl-3-(p-tolyl)prop-2-yn-1-amine
N-Benzyl-1-phenyl-3-(p-tolyl)prop-2-yn-1-amine was synthesized according to the general procedure.28
The crude was purified by flash column chromatography using hexane/ethyl acetate (9:1) as eluent to give
the desired amine (280 mg, 45% yield) as viscous yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J =
7.3 Hz, 2H), 7.48–7.41 (m, 5H), 7.40–7.35 (m, 3H), 7.35–7.26 (m, 2H), 7.17 (d, J = 7.9 Hz, 2H), 4.84 (s,
1H), 4.08–3.98 (m, 2H), 2.40 (s, 3H), 1.91 (bs, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 140.5, 139.9,
138.4, 131.8, 129.2, 128.61 (2C), 128.56, 127.9, 127.8, 127.2, 120.2, 88.5, 86.0, 53.8, 51.2, 21.6. HRMS
(ESI) calcd for C23H22N (M+H)+ m/z 312.1752, found m/z 312.1751.
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N-Benzyl-3-(4-chlorophenyl)-1-phenylprop-2-yn-1-amine
N-Benzyl-3-(4-chlorophenyl)-1-phenylprop-2-yn-1-amine was synthesized according to the general
procedure.28 The crude was purified by flash column chromatography using hexane/ethyl acetate (8:2) as
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eluent to give the desired amine (358 mg, 54% yield) as viscous dark yellow oil. H NMR (400 MHz,
CDCl3) δ 7.64 (d, J = 7.3 Hz, 2H), 7.47–7.38 (m,7H), 7.38–7.27 (m, 5H), 4.84 (s, 1H), 4.09–3.94 (m, 2H),
2.01 (bs, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 140.2, 139.8, 134.3, 133.1, 128.8, 128.7, 128.6, 128.5,
128.0, 127.7, 127.2, 121.6, 90.5, 84.7, 53.8, 51.3. HRMS (ESI) calcd for C22H19ClN (M+H)+ m/z
332.1206, found m/z 332.1207.
N-Benzyl-3-(4-fluorophenyl)-1-phenylprop-2-yn-1-amine
N-Benzyl-3-(4-fluorophenyl)-1-phenylprop-2-yn-1-amine was synthesized according to the general
procedure.28 The crude was purified by flash column chromatography using hexane/ethyl acetate (8:2) as
eluent to give the desired amine (265 mg, 42% yield) as viscous yellow oil. 1H NMR (400 MHz, CDCl3)
δ 7.69–7.62 (m, 2H), 7.54–7.48 (m, 2H), 7.48–7.34 (m, 7H), 7.33–7.28 (m, 1H), 7.10–7.01 (m, 2H), 4.84
(s, 1H), 4.11–3.96 (m, 2H), 1.89 (s, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 162.51 (d, JC,F = 249.2 Hz),
140.35, 139.84, 133.67 (d, JC,F = 8.3 Hz), 128.64, 128.55, 128.51, 127.93, 127.73, 127.23, 119.27 (d, JC,F
= 3.5 Hz), 115.62 (d, JC,F = 22.0 Hz), 89.05, 84.72, 53.73, 51.26. 19F{1H} NMR (376 MHz, CDCl3) δ -
111.03. HRMS (ESI) calcd for C22H19FN (M+H)+ m/z 316.1501, found m/z 332.1498.
1-(2-Methylbut-3-yn-2-yl)-3-phenylurea (1a)
Compound 1a was synthesized according to the general procedure.25 The crude was dried under vacuum
and used without purification. Compound 1a was obtained as white solid; m.p. (hexane) 116.3–117.6 °C.
1H NMR (400 MHz, DMSO-d6) δ 8.28 (bs, 1H), 7.36 (d further split, 2H), 7.26–7.17 (m, 2H), 6.95–6.83
(m, 1H), 6.38 (bs, 1H), 3.10 (s, 1H), 1.54 (s, 6H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 153.8, 140.2,
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128.6, 121.1, 117.5, 88.5, 70.7, 46.0, 29.3. HRMS (ESI) calcd for C12H14N2NaO (M+Na)+ m/z 225.1004,
found m/z 225.1008.
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1-(2-Methylbut-3-yn-2-yl)-3-(p-tolyl)urea (1b)
Compound 1b was synthesized according to the general procedure.25 The crude was dried under vacuum
and used without purification. Compound 1b was obtained as white solid; m.p. (hexane) 144.4–146.1 °C.
1H NMR (400 MHz, DMSO-d6) δ 8.19 (bs, 1H), 7.25 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 8.3 Hz, 2H), 6.34
(bs, 1H), 3.11 (s, 1H), 2.22 (s, 3H), 1.54 (s, 6H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 153.9, 137.7,
129.8, 129.0, 117.6, 88.7, 70.7, 46.0, 29.4, 20.3. HRMS (ESI) calcd for C13H16N2NaO (M+Na)+ m/z
239.1160, found m/z 239.1158.
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1-(4-Fluorophenyl)-3-(2-methylbut-3-yn-2-yl)urea (1c)
Compound 1c was synthesized according to the general procedure.25 The crude was dried under vacuum
and used without purification. Compound 1c was obtained as light purple solid; m.p. (hexane) 174.1–
174.8 °C. 1H NMR (400 MHz, DMSO-d6) δ 8.33 (bs, 1H), 7.41–7.30 (m, 2H), 7.09–7.01 (m, 2H), 6.38
(bs, 1H), 3.11 (s, 1H), 1.53 (s, 6H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 156.9 (d, JC,F = 237.2 Hz),
153.9, 136.6 (d, JC,F = 2.3 Hz), 119.1 (d, JC,F = 7.5 Hz), 115.1 (d, JC,F = 22.0 Hz), 88.6, 70.8, 46.0, 29.4.
19F{1H} NMR (376 MHz, DMSO-d6) δ -122.40. HRMS (ESI) calcd for C12H13FN2NaO (M+Na)+ m/z
243.0910, found m/z 243.0912.
Methyl 4-(3-(2-methylbut-3-yn-2-yl)ureido)benzoate (1d)
Compound 1d was synthesized according to the general procedure.25 The crude was dried under vacuum
and used without purification. Compound 1d was obtained as white solid; m.p. (hexane) 189.6–190.9 °C.
1H NMR (400 MHz, DMSO-d6) δ 8.73 (bs, 1H), 7.86–7.81 (m, 2H), 7.52–7.48 (m, 2H), 6.58 (bs, 1H),
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3.79 (s, 3H), 3.10 (s, 1H), 1.55 (s, 6H). C{1H} NMR (101 MHz, DMSO-d6) δ 166.0, 153.4, 144.9,
130.4, 121.9, 116.7, 88.3, 70.8, 51.6, 46.2, 29.2. HRMS (ESI) calcd for C14H16N2NaO3 (M+Na)+ m/z
283.1059, found m/z 283.1057.
1-(3-Ethylpent-1-yn-3-yl)-3-phenylurea (1e)
Compound 1e was synthesized according to the general procedure.25 The crude was dried under vacuum
and used without purification. Compound 1e was obtained as white solid; m.p. (hexane) 122.3–123.1 °C.
1H NMR (400 MHz, CDCl3) δ 7.98 (bs, 1H), 7.35 (d, J = 7.6 Hz, 2H), 7.21 (t, J = 7.9 Hz, 2H), 6.97 (t,
J=7.4 Hz, 1H), 5.85 (bs, 1H), 2.32 (s, 1H), 2.01–1.78 (m, 2H), 1.76–1.53 (m, 2H), 0.99 (t, J = 7.4 Hz,
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6H). 13C{1H} NMR (101 MHz, CDCl3) δ 155.5, 139.2, 128.9, 122.8, 119.8, 85.8, 71.8, 55.6, 31.4, 8.5.
HRMS (ESI) calcd for C14H18N2NaO (M+Na)+ m/z 253.1317, found m/z 253.1320.
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1-(1-Ethynylcyclohexyl)-3-phenylurea (1f)
Compound 1f was synthesized according to the general procedure.25 The crude was dried under vacuum
and used without purification. Compound 1f was obtained as white solid; m.p. (hexane) 157.2–157.8 °C.
1H NMR (400 MHz, DMSO-d6) δ 8.32 (bs, 1H), 7.36 (d, J = 7.6 Hz, 2H), 7.22 (t, J = 7.9 Hz, 2H), 6.89
(t, J = 7.3 Hz, 1H), 6.29 (bs, 1H), 3.15 (s, 1H), 2.08–1.92 (m, 2H), 1.81–1.69 (m, 2H), 1.62–1.43 (m, 5H),
1.34–1.22 (m, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 154.2, 140.8, 129.1, 121.5, 117.9, 87.6, 73.3,
50.6, 37.3, 25.3, 22.4. HRMS (ESI) calcd for C15H18N2NaO (M+Na)+ m/z 265.1317, found m/z 265.1319.
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1-Benzyl-1-(2-methylbut-3-yn-2-yl)-3-phenylurea (1g)
Compound 1g was synthesized according to the general procedure.27 Compound 1g was obtained as
colorless oil; 1H NMR (300 MHz, CDCl3) δ 7.47–7.41 (m, 4H), 7.37–7.31 (m, 2H), 7.29–7.23 (m, 4H),
6.95 (bs, 1H), 4.85 (s, 2H), 2.56 (s, 1H), 1.88 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 156.2, 139.3,
139.2, 129.2, 128.9, 127.6, 126.5, 123.1, 119.8, 88.1, 72.8, 54.8, 50.1, 29.2. HRMS (ESI) calcd for
C19H20N2NaO (M+Na)+ m/z 315.1473, found m/z 315.1476.
1-Benzyl-1-(2-methyldodec-3-yn-2-yl)-3-phenylurea (1h)
Compound 1h was synthesized according to the general procedure.26 The crude was purified by silica gel
column chromatography to obtain 1h with 78% yield (352 mg) as a yellowish oil. 1H NMR (400 MHz,
CDCl3) δ 7.51 (bs, 1H), 7.44–7.34 (m, 4H), 7.33–7.24 (m, 5H), 7.05–6.98 (m, 1H), 4.87 (s, 2H), 2.21 (t,
J = 7.0 Hz, 2H), 1.80 (s, 6H), 1.49–1.39 (m, 2H), 1.37–1.19 (m, 10H), 0.91 (t, J = 7.0 Hz, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ 156.4, 140.1, 139.5, 128.9, 128.8, 127.2, 126.6, 122.8, 119.6, 85.9, 84.6, 54.6,
49.4, 31.9, 29.8, 29.3, 29.2, 29.0, 28.6, 22.8, 18.8, 14.2. HRMS (ESI) calcd for C27H37N2O (M+H)+ m/z
405.2906, found m/z 405.2908.
1-(2-Methyl-4-phenylbut-3-yn-2-yl)-3-phenylurea (1i)
Compound 1i was synthesized according to the general procedure.26 The crude was purified by silica gel
column chromatography to obtain 1i with 78% yield (217 mg) as a yellowish solid; m.p. (hexane) 182.3–
183.7 °C. 1H NMR (400 MHz, DMSO-d6) δ 8.36 (bs, 1H), 7.45–7.30 (m, 7H), 7.23 (t, J = 7.9 Hz, 2H),
6.90 (t, J = 7.3 Hz, 1H), 6.53 (bs, 1H), 1.66 (s, 6H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 153.8, 140.2,
131.2, 128.6, 128.4, 128.1, 122.6, 121.0, 117.5, 94.5, 79.6, 46.6, 29.4. HRMS (ESI) calcd for
C18H18N2NaO (M+Na)+ m/z 301.1317, found m/z 301.1313.
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1-(2-Methyl-4-(4-(trifluoromethyl)phenyl)but-3-yn-2-yl)-3-phenylurea (1j)
Compound 1j was synthesized according to the general procedure.26 The crude was purified by silica gel
column chromatography to obtain 1j with 91% yield (315 mg) as a white solid; m.p. (hexane) 183.9–
185.2 °C. 1H NMR (400 MHz, DMSO-d6) δ 8.38 (bs, 1H), 7.68 (d, J = 8.3 Hz, 2H), 7.58 (d, J = 8.2 Hz,
2H), 7.43 (d, J = 7.6 Hz, 2H), 7.23 (t, J = 7.9 Hz, 2H), 6.90 (t, J = 7.3 Hz, 1H), 6.58 (bs, 1H), 1.68 (s,
6H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 153.9, 140.2, 132.0, 128.6, 128.3 (q, JC,F = 32.1 Hz), 127.1
(q, JC,F = 1.2 Hz), 125.4 (q, JC,F = 3.6 Hz), 124.0 ( q, JC,F = 271.9 Hz), 121.2, 117.7, 97.4, 78.5, 46.6, 29.3.
19F{1H} NMR (376 MHz, DMSO-d6) δ -61.47. HRMS (ESI) calcd for C19H17F3N2NaO (M+Na)+ m/z
369.1191, found m/z 369.1194.
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1-(4-(4-Methoxyphenyl)-2-methylbut-3-yn-2-yl)-3-phenylurea (1k)
Compound 1k was synthesized according to the general procedure.26 The crude was purified by silica gel
column chromatography to obtain 1k with 57% yield (176 mg) as pale yellow solid; m.p. (hexane) 178.2–
178.6 °C. 1H NMR (400 MHz, DMSO-d6) δ 8.35 (bs, 1H), 7.41 (d, J = 7.8 Hz, 2H), 7.32 (d, J = 8.7 Hz,
2H), 7.23 (t, J = 7.8 Hz, 2H), 6.95–6.86 (m, 3H), 6.51 (bs, 1H), 3.74 (s, 3H), 1.66 (s, 6H). 13C{1H} NMR
(101 MHz, DMSO-d6) δ 159.1, 153.9, 140.3, 132.8, 128.7, 121.1, 117.6, 114.7, 114.1, 93.0, 79.6, 55.1,
46.8, 29.6. HRMS (ESI) calcd for C19H20N2NaO2 (M+Na)+ m/z 331.1422, found m/z 331.1424.
1-(2-Methyl-4-(thiophen-2-yl)but-3-yn-2-yl)-3-phenylurea (1l)
Compound 1l was synthesized according to the general procedure.26 The crude was purified by silica gel
column chromatography to obtain 1l with 94% yield (267 mg) as a yellowish solid; m.p. (hexane) 210.3–
211.4 °C. 1H NMR (400 MHz, DMSO-d6) δ 8.36 (bs, 1H), 7.51 (d, J = 4.9 Hz, 1H), 7.41 (d, J = 7.9 Hz,
2H), 7.26–7.18 (m, 3H), 7.04–6.99 (m, 1H), 6.91 (t, J = 7.3 Hz, 1H), 6.55 (bs, 1H), 1.65 (s, 6H). 13C{1H}
NMR (101 MHz, DMSO-d6) δ 153.9, 140.2, 131.8, 128.7, 127.7, 127.4, 122.4, 121.2, 117.6, 98.3, 73.1,
46.8, 29.4. HRMS (ESI) calcd for C16H16N2NaOS (M+Na)+ m/z 307.0881, found m/z 307.0883.
Ethyl 2-(3-(2-methylbut-3-yn-2-yl)ureido)acetate (1m)
Compound 1m was synthesized according to the general procedure.25 The crude was dried under vacuum
and used without purification. Compound 1m was obtained as white solid; m.p. (hexane) 83.2–84.8 °C.
1H NMR (400 MHz, CDCl3) δ 4.19 (q, J = 7.1 Hz, 2H), 4.01 (s, 2H), 2.42 (s, 1H), 1.59 (s, 6H), 1.27 (t, J
= 7.1 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.3, 157.2, 87.5, 70.4, 61.4, 46.9, 42.2, 30.1, 14.3.
HRMS (ESI) calcd for C10H16N2NaO3 (M+Na)+ m/z 235.1059, found m/z 235.1058.
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1-Benzyl-1-(1,3-diphenylprop-2-yn-1-yl)-3-phenylurea (3a)
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Compound 3a was synthesized according to the general procedure.25 The crude was dried under vacuum
and used without purification. Compound 3a was obtained as yellow solid; m.p. (hexane) 96.2–97.7 °C.
The spectroscopic data of 3a were consistent with literature values.34 1H NMR (400 MHz, CDCl3) δ 7.86–
7.81 (m, 2H), 7.54–7.37 (m, 13H), 7.33–7.25 (m, 4H), 7.15 (s, 1H), 7.12–7.03 (m, 1H), 6.59 (bs, 1H),
4.76 (d, J = 17.1 Hz, 1H), 4.57 (d, J = 17.1 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 155.5, 138.7,
138.0, 137.1, 131.6, 129.1, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.0, 127.7, 127.0, 123.1, 122.3,
119.7, 86.9, 86.0, 51.3, 48.5. HRMS (ESI) calcd for C29H25N2O (M+H)+ m/z 417.1967, found m/z
417.1970.
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1-Benzyl-3-phenyl-1-(1-phenylundec-2-yn-1-yl)urea (3b)
Compound 3b was synthesized according to the general procedure.25 The crude was dried under vacuum
and used without purification. Compound 3b was obtained as orange oil. 1H NMR (400 MHz, CDCl3) δ
7.72 (d, J = 7.5 Hz, 2H), 7.48–7.35 (m, 8H), 7.33–7.12 (m, 4H), 7.03 (t, J = 7.1 Hz, 1H), 6.75 (s, 1H),
6.52 (s, 1H), 4.68 (d, J = 16.8 Hz, 1H), 4.48 (d, J = 16.9 Hz, 1H), 2.35 (t, J = 6.7 Hz, 2H), 1.63–1.52 (m,
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2H), 1.51–1.25 (m, 10H), 0.99 (t, J = 6.8 Hz, 3H). C{1H} NMR (101 MHz, CDCl3) δ 155.5, 138.8,
138.6, 137.4, 128.9, 128.7, 128.6, 128.0, 127.9, 127.6, 127.2, 123.0, 119.7, 87.8, 76.7, 51.1, 48.6, 31.8,
29.2, 29.1, 28.9, 28.5, 22.6, 18.7, 14.1. HRMS (ESI) calcd for C31H37N2O (M+H)+ m/z 453.2906, found
m/z 453.2909.
1-Butyl-1-(1,3-diphenylprop-2-yn-1-yl)-3-phenylurea (3c)
Compound 3c was synthesized according to the general procedure.25 The crude was dried under vacuum
and used without purification. Compound 3c was obtained as yellowish oil. 1H NMR (400 MHz, CDCl3)
δ 7.69–7.64 (m, 2H), 7.55–7.50 (m, 2H), 7.44–7.33 (m, 8H), 7.32–7.27 (m, 2H), 7.08–7.02 (m, 1H), 6.67
(s, 1H), 6.58 (s, 1H), 3.48–3.30 (m, 2H), 1.87–1.73 (m, 1H), 1.61–1.43 (m, 1H), 1.42–1.26 (m, 2H), 0.91
(t, J = 7.3 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 154.9, 139.0, 138.1, 131.8, 129.0, 128.8, 128.7,
128.5, 128.2, 127.5, 123.2, 122.6, 120.0, 86.8, 86.1, 51.3, 45.5, 31.5, 20.4, 13.9. HRMS (ESI) calcd for
C26H27N2O (M+H)+ m/z 383.2123, found m/z 383.2120.
1-(1,3-Diphenylprop-2-yn-1-yl)-3-phenyl-1-(1-phenylethyl)urea (3d)
Compound 3d was synthesized according to the general procedure.25 Compound 3d was obtained as
colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 7.6 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H), 7.55–7.45
(m, 4H), 7.45–7.30 (m, 6H), 7.29–7.22 (m, 3H), 7.14 (t, J = 7.8 Hz, 2H), 7.03 (t, J = 7.3 Hz, 1H), 6.92
(bs, 1H), 6.36 (s, 1H), 5.52–5.48 (m, 1H), 1.44 (d, J = 7.1 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
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154.6, 140.9, 138.8, 138.2, 131.6, 129.0, 128.7 (2C), 128.6, 128.45, 128.36, 128.3, 128.1, 127.7, 127.2,
122.9, 119.4, 86.9, 86.5, 52.0, 50.7, 17.2. HRMS (ESI) calcd for C30H27N2O(M+H)+ m/z 431.2123, found
m/z 431.2121.
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1-(1,3-Diphenylprop-2-yn-1-yl)-1-(4-methylbenzyl)-3-phenylurea (3e)
Compound 3e was synthesized according to the general procedure.25 Compound 3e was obtained as
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orange solid; m.p. (hexane) 109.8–111.2 °C. H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 7.5 Hz, 2H),
7.55–7.48 (m, 4H), 7.45 (d, J = 7.2 Hz, 1H), 7.41–7.35 (m, 5H), 7.32–7.29 (m, 4H), 7.26 (d, J = 7.9 Hz,
2H), 7.18 (s, 1H), 7.10–7.04 (m, 1H), 6.67 (bs, 1H), 4.72 (d, J = 16.9 Hz, 1H), 4.52 (d, J = 16.9 Hz, 1H),
2.43 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 155.5, 138.8, 138.0, 137.6, 134.0, 131.6, 129.7, 128.7,
128.6, 128.5, 128.2, 128.1, 127.6, 127.0, 123.0, 122.3, 119.6, 86.8, 86.1, 51.2, 48.1, 21.0. HRMS (ESI)
calcd for C30H27N2O (M+H)+ m/z 431.2123, found m/z 431.2119.
1-(1,3-Diphenylprop-2-yn-1-yl)-1-(4-fluorobenzyl)-3-phenylurea (3f)
Compound 3f was synthesized according to the general procedure.25 Compound 3f was obtained as light
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orange solid; m.p. (hexane) 125.6–126.8 °C. H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.6 Hz, 2H),
7.51–7.45 (m, 4H), 7.44–7.36 (m, 6H), 7.32–7.23 (m, 4H), 7.13–7.04 (m, 3H), 7.00 (s, 1H), 6.53 (bs, 1H),
4.70 (d, J = 17.0 Hz, 1H), 4.54 (d, J = 17.0 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 162.4 (d, J =
246.7 Hz), 155.4, 138.7, 137.9, 133.0 (d, J = 3.1 Hz), 131.7, 128.9 (d, J = 7.8 Hz), 128.8 (2C), 128.7,
128.4, 127.7, 123.4, 122.3, 119.9, 116.0 (d, J = 21.5 Hz), 87.1, 85.9, 51.5, 48.0. 19F{1H} NMR (376 MHz,
CDCl3) δ -113.93. HRMS (ESI) calcd for C29H24FN2O (M+H)+ m/z 435.1873, found m/z 435.1875.
1-Benzyl-3-phenyl-1-(3-phenyl-1-(p-tolyl)prop-2-yn-1-yl)urea (3g)
Compound 3g was synthesized according to the general procedure.25 Compound 3g was obtained as light
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yellow oil. H NMR (400 MHz, CDCl3) δ 7.68–7.61 (m, 2H), 7.54–7.46 (m, 6H), 7.45–7.37 (m, 5H),
7.33–7.25 (m, 5H), 7.12–7.05 (m, 2H), 6.60 (bs, 1H), 4.78 (d, J = 17.0 Hz, 1H), 4.59 (d, J = 17.1 Hz, 1H),
2.49 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 155.4, 138.8, 138.4, 137.9, 137.2, 131.6, 129.1, 129.0,
128.7, 128.6, 128.5, 128.4, 128.3, 128.0, 127.1, 124.8, 123.1, 122.4, 119.7, 86.8, 86.2, 51.3, 48.5, 21.5.
HRMS (ESI) calcd for C30H27N2O (M+H)+ m/z 431.2123, found m/z 431.2121.
1-Benzyl-1-(1-(4-methoxyphenyl)-3-phenylprop-2-yn-1-yl)-3-phenylurea (3h)
Compound 3h was synthesized according to the general procedure.25 Compound 3h was obtained as
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yellow oil. H NMR (400 MHz, CDCl3) δ 7.72–7.67 (m, 2H), 7.47–7.40 (m, 6H), 7.39–7.32 (m, 4H),
7.29–7.24 (m, 2H), 7.22–7.18 (m, 2H), 7.07–6.97 (m, 4H), 6.48 (bs, 1H), 4.71 (d, J = 17.0 Hz, 1H), 4.52
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(d, J = 17.0 Hz, 1H), 3.86 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 159.6, 155.6, 138.8, 137.3, 131.7,
130.2, 129.2, 129.1, 128.8, 128.6, 128.4, 128.1, 127.2, 123.2, 122.5, 119.8, 114.1, 86.8, 86.4, 55.3, 50.8,
48.5. HRMS (ESI) calcd for C30H27N2O2 (M+H)+ m/z 447.2072, found m/z 447.2075.
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1-Benzyl-1-(1-(3-chlorophenyl)-3-phenylprop-2-yn-1-yl)-3-phenylurea (3i)
Compound 3i was synthesized according to the general procedure.25 Compound 3i was obtained as orange
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oil. H NMR (400 MHz, CDCl3) δ 7.82 (s, 1H), 7.72–7.67 (m, 1H), 7.51–7.44 (m, 6H), 7.42–7.35 (m,
6H), 7.32–7.23 (m, 4H), 7.13 (s, 1H), 7.10–7.05 (m, 1H), 6.62 (bs, 1H), 4.73 (d, J = 17.2 Hz, 1H), 4.53
(d, J = 17.2 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 155.5, 140.2, 138.5, 136.8, 134.6, 131.6, 130.0,
129.1, 128.8, 128.7, 128.4, 128.3, 128.1, 127.8, 126.9, 125.9, 123.4, 122.0, 120.0, 87.4, 85.2, 50.8, 48.3.
HRMS (ESI) calcd for C29H24ClN2O (M+H)+ m/z 451.1577, found m/z 451.1578.
1-Benzyl-3-phenyl-1-(3-phenyl-1-(3-vinylphenyl)prop-2-yn-1-yl)urea (3j)
Compound 3j was synthesized according to the general procedure.25 Compound 3j was obtained as orange
oil. 1H NMR (400 MHz, CDCl3) δ 7.81 (s, 1H), 7.69 (d, J = 7.4 Hz, 1H), 7.50–7.35 (m, 12H), 7.30–7.25
(m, 2H), 7.24–7.21 (m, 2H), 7.09 (brs, 1H), 7.08–7.03 (m, 1H), 6.83 (dd, J = 17.6, 10.9 Hz, 1H), 6.53 (bs,
1H), 5.87 (d, J = 17.6 Hz, 1H), 5.36 (d, J = 11.2 Hz, 1H), 4.73 (d, J = 17.0 Hz, 1H), 4.54 (d, J = 17.1 Hz,
1H). 13C{1H} NMR (101 MHz, CDCl3) δ 155.6, 138.7, 138.4, 138.1, 137.1, 136.5, 131.7, 129.2, 129.0,
128.8, 128.6, 128.4, 128.1, 127.2, 127.1, 126.0, 125.8, 123.3, 122.4, 119.8, 114.6, 87.1, 85.9, 51.3, 48.6.
HRMS (ESI) calcd for C31H27N2O (M+H)+ m/z 443.2123, found m/z 443.2127.
1-Benzyl-1-(1-(2-bromophenyl)-3-phenylprop-2-yn-1-yl)-3-phenylurea (3k)
Compound 3k was synthesized according to the general procedure.25 Compound 3k was obtained as
yellow solid; m.p. (hexane) 124.7–126.1 °C. 1H NMR (400 MHz, CDCl3) δ 7.97 (dd, J = 7.7, 1.6 Hz, 1H),
7.68 (dd, J = 7.9, 1.2 Hz, 1H), 7.55–7.51 (m, 2H), 7.41–7.34 (m, 6H), 7.33–7.24 (m, 8H), 7.09 (s, 1H),
7.06–7.01 (m, 1H), 6.59 (bs, 1H), 4.62 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 155.5, 138.8, 137.2,
136.6, 133.6, 131.8, 130.8, 130.1, 129.1, 128.8, 128.7, 128.4, 127.9, 127.6, 126.9, 124.6, 123.1, 122.3,
119.7, 87.0, 85.8, 52.2, 48.3. HRMS (ESI) calcd for C29H24BrN2O (M+H)+ m/z 495.1072, found m/z
495.1074.
1-Benzyl-1-(1,3-diphenylprop-2-yn-1-yl)-3-propylurea (3l)
Compound 3l was synthesized according to the general procedure.25 Compound 3l was isolated as yellow
oil in 45% yield (172 mg). 1H NMR (300 MHz, CDCl3) δ 7.70–7.64 (m, 2H), 7.44–7.24 (m, 13H), 6.98
(bs, 1H), 4.54 (d, J = 17.1 Hz, 1H), 4.41–4.34 (m, 1H), 4.31 (d, J = 17.1 Hz, 1H), 3.26–3.04 (m, 2H),
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1.40–1.25 (m, 2H), 0.69 (t, J = 7.4 Hz, 3H). C{1H} NMR (75 MHz, CDCl3) δ 158.2, 138.6, 137.9,
131.7, 128.9, 128.7, 128.5, 128.4, 128.1, 127.8, 127.7, 126.9, 122.7, 86.7, 86.56, 51.4, 48.3, 42.8, 23.2,
11.1. HRMS (ESI) calcd for C26H27N2O (M+H)+ m/z 383.2123, found m/z 383.2126.
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Compound 3m was synthesized according to the general procedure.25 Compound 3m was isolated as
yellow oil in 62% yield (267 mg). 1H NMR (300 MHz, CDCl3) δ 7.77–7.70 (m, 2H), 7.48–7.30 (m, 12H),
7.28–7.22 (m, 3H), 7.06–7.00 (m, 3H), 4.84 (t, J = 5.5 Hz, 1H), 4.63 (d, J = 17.2 Hz, 1H), 4.54–4.35 (m,
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3H). C{1H} NMR (75 MHz, CDCl3) δ 157.9, 139.1, 138.4, 137.6, 131.7, 128.9, 128.7, 128.5, 128.4,
128.3, 128.1, 127.7, 127.6, 127.1, 127.0, 126.9, 122.6, 86.8, 86.3, 51.5, 48.3, 44.9. HRMS (ESI) calcd for
C30H27N2O (M+H)+ m/z 431.2123, found m/z 431.2121.
1-Benzyl-3-phenyl-1-(1-phenyl-3-(p-tolyl)prop-2-yn-1-yl)urea (3n)
Compound 3n was synthesized according to the general procedure.25 Compound 3n was obtained as
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yellowish solid; m.p. (hexane) 53.6–54.2 °C. H NMR (400 MHz, CDCl3) δ 7.79–7.72 (m, 2H), 7.49–
7.32 (m, 10H), 7.28–7.23 (m, 2H), 7.21–7.13 (m, 4H), 7.06–6.99 (m, 2H), 6.45 (bs, 1H), 4.71 (d, J = 17.0
Hz, 1H), 4.50 (d, J = 17.0 Hz, 1H), 2.40 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 155.6, 138.9, 138.8,
138.3, 137.3, 131.7, 129.3, 129.2, 128.9, 128.8, 128.3, 128.2, 127.8, 127.2, 123.2, 119.8, 119.4, 87.2,
85.4, 51.5, 48.7, 21.6. HRMS (ESI) calcd for C30H27N2O (M+H)+ m/z 431.2123, found m/z 431.2124.
1-Benzyl-1-(3-(4-chlorophenyl)-1-phenylprop-2-yn-1-yl)-3-phenylurea (3o)
Compound 3o was synthesized according to the general procedure.25 Compound 3o was obtained as
yellow viscous oil. 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.5 Hz, 2H), 7.50–7.29 (m, 12H), 7.28–
7.22 (m, 2H), 7.21–7.15 (m, 2H), 7.10–7.00 (m, 2H), 6.44 (bs, 1H), 4.68 (d, J = 17.1 Hz, 1H), 4.51 (d, J
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= 17.1 Hz, 1H). C{1H} NMR (101 MHz, CDCl3) δ 155.6, 138.8, 137.9, 137.2, 134.7, 133.0, 129.3,
128.9, 128.8, 128.4, 128.2, 127.8, 127.1, 123.3, 121.0, 119.9, 87.2, 85.9, 51.4, 48.6. HRMS (ESI) calcd
for C29H24ClN2O (M+H)+ m/z 451.1577, found m/z 451.1579.
1-Benzyl-1-(3-(4-fluorophenyl)-1-phenylprop-2-yn-1-yl)-3-phenylurea (3p)
Compound 3p was synthesized according to the general procedure.25 Compound 3p was obtained as
viscous yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 7.5 Hz, 2H), 7.56–7.35 (m, 10H), 7.33–
7.22 (m, 4H), 7.13 (s, 1H), 7.10–7.00 (m, 3H), 6.60 (bs, 1H), 4.74 (d, J = 17.1 Hz, 1H), 4.58 (d, J = 17.1
Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 162.6 (d, JC,F = 249.9 Hz), 155.5, 138.8, 137.9, 137.2, 133.6
(d, JC,F = 8.4 Hz), 129.1, 128.7 (2C), 128.2, 127.9, 127.7, 127.0, 123.2, 119.8, 118.5 (d, JC,F = 3.5 Hz),
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115.6 (d, JC,F = 22.1 Hz), 85.8 (2C), 51.2, 48.4. F{1H} NMR (376 MHz, CDCl3) δ -110.00. HRMS
(ESI) calcd for C29H24FN2O (M+H)+ m/z 435.1873, found m/z 435.1872.
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4,4-Dimethyl-5-methylene-1-phenylimidazolidin-2-one (2a)
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Compound 2a was obtained from 1a in 1 hour, according to the general procedure. The crude was purified
by flash column chromatography using hexane/ethyl acetate (1:1) as eluent to give 2a (78 mg, 97% yield)
as white solid; m.p. (hexane) 127.5–130.1 °C. 1H NMR (400 MHz, CDCl3) δ 7.48–7.42 (m, 2H), 7.35–
7.30 (m, 3H), 6.23 (bs, 1H), 4.03, 3.97 (2 partly overlapping bs, 2H), 1.46 (s, 6H). 13C{1H} NMR (101
MHz, CDCl3) δ 157.2, 154.68, 135.2, 129.4, 127.7, 127.6, 79.6, 56.7, 29.9. HRMS (ESI) calcd for
C12H15N2O (M+H)+ m/z 203.1184, found m/z 203.1182.
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4,4-Dimethyl-5-methylene-1-(p-tolyl)imidazolidin-2-one (2b)
Compound 2b was obtained from 1b in 16 hours, according to the general procedure. The crude was
purified by flash column chromatography using hexane/ethyl acetate (1:1) as eluent to give 2b (69 mg,
82% yield) as pale orange solid; m.p. (hexane) 195.2–197.3 °C. 1H NMR (400 MHz, CDCl3) δ 7.27 (d, J
= 8.0 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H), 5.83 (bs, 1H), 4.02 (d, J = 2.1 Hz, 1H), 3.97 (d, J = 2.3 Hz, 1H),
2.39 (s, 3H), 1.48 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 157.3, 154.9, 137.6, 132.5, 130.1, 127.6,
79.5, 56.7, 29.9, 21.3. HRMS (ESI) calcd for C13H17N2O (M+H)+ m/z 217.1341, found m/z 217.1344.
1-(4-Fluorophenyl)-4,4-dimethyl-5-methyleneimidazolidin-2-one (2c)
Compound 2c was obtained from 1c in 1 hour and 30 minutes, according to the general procedure. The
crude was purified by flash column chromatography using hexane/ethyl acetate (1:1) as eluent to give 2c
(86 mg, 97% yield) as orange solid; m.p. (hexane) 165.6–167.0 °C. 1H NMR (400 MHz, CDCl3) δ 7.33–
7.25 (m, 2H), 7.17–7.08 (m, 2H), 5.89 (bs, 1H), 4.03, 3.97 (2 bs, 2H), 1.46 (s, 6H). 13C{1H} NMR (101
MHz, CDCl3) δ 161.7 (d, JC,F = 247.1 Hz), 157.1, 154.7, 131.1 (d, JC,F = 3.1 Hz), 129.6 (d, JC,F = 8.6 Hz),
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116.4 (d, JC,F = 22.8 Hz), 79.9, 56.8, 29.9. F{1H} NMR (376 MHz, CDCl3) δ -113.93. HRMS (ESI)
calcd for C12H14FN2O (M+H)+ m/z 221.1090, found m/z 221.1086.
Methyl 4-(4,4-dimethyl-5-methylene-2-oxoimidazolidin-1-yl)benzoate (2d)
Compound 2d was obtained from 1d in 6 hours, according to the general procedure. The crude was
purified by flash column chromatography using hexane/ethyl acetate (1:1) as eluent to give 2d (102 mg,
98% yield) as yellowish solid; m.p. (hexane) 218.0–220.3 °C. 1H NMR (400 MHz, CDCl3) δ 8.14–8.07
(m, 2H), 7.48–7.40 (m, 2H), 6.34 (bs, 1H), 4.17 (dd, J = 2.6, 0.8 Hz, 1H), 4.04 (d, J = 2.6 Hz, 1H), 3.91
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(s, 3H), 1.45 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 166.5, 156.6, 153.5, 139.6, 130.7, 128.6, 127.0,
80.6, 56.8, 52.3, 29.8. HRMS (ESI) calcd for C14H17N2O3 (M+H)+ m/z 261.1240, found m/z 261.1242.
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Compound 2e was obtained from 1e in 3 hours, according to the general procedure. The crude was purified
by flash column chromatography using hexane/ethyl acetate (1:1) as eluent to give 2e (92 mg, 99% yield)
as pale orange solid; m.p. (hexane) 120.5–122.2 °C. 1H NMR (400 MHz, CDCl3) δ 7.48–7.42 (m, 2H),
7.36–7.31 (m, 1H), 7.30–7.27 (m, 2H), 5.32 (bs, 1H), 4.13 (dd, J = 2.3, 0.8 Hz, 1H), 3.87 (d, J = 2.3 Hz,
1H), 1.75–1.57 (m, 4H), 0.97 (t, J = 7.3 Hz, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 157.9, 150.9, 135.2,
129.5, 127.8, 127.7, 80.2, 63.6, 34.1, 7.8. HRMS (ESI) calcd for C14H19N2O(M+H)+ m/z 231.1497, found
m/z 231.1499.
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4-methylene-3-phenyl-1,3-diazaspiro[4.5]decan-2-one (2f)
Compound 2f was obtained from 1f in 16 hours, according to the general procedure. The crude was
purified by flash column chromatography using hexane/ethyl acetate (1:1) as eluent to give 2f (92 mg,
95% yield) as white solid; m.p. (hexane) 175.2–176.7 °C. 1H NMR (400 MHz, CDCl3) δ 7.47–7.41 (m,
2H), 7.34–7.29 (m, 3H), 6.07 (bs, 1H), 4.07 (d, J = 2.3 Hz, 1H), 3.96 (d, J = 2.3 Hz, 1H), 1.92–1.83 (m,
2H), 1.81–1.70 (m, 2H), 1.63–1.53 (m, 2H), 1.49–1.35 (m, 2H), 1.35–1.21 (m, 2H). 13C{1H} NMR (101
MHz, CDCl3) δ 157.2, 154.5, 135.1, 129.4, 127.7, 127.6, 80.2, 59.5, 38.6, 25.0, 22.4. HRMS (ESI) calcd
for C15H19N2O (M+H)+ m/z 243.1497, found m/z 243.1500.
3-Benzyl-4,4-dimethyl-5-methylene-1-phenylimidazolidin-2-one (2g)
Compound 2g was obtained from 1g in 16 hours, according to the general procedure. The crude was
purified by flash column chromatography using hexane/ethyl acetate (7:3) as eluent to give 2g (61 mg,
52% yield) as colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 7.2 Hz, 2H), 7.39–7.25 (m, 5H),
7.20–7.16 (m, 2H), 7.06–7.00 (m, 1H), 4.64 (d, J = 3.3 Hz, 1H), 4.63 (s, 2H), 4.20 (d, J = 3.3 Hz, 1H),
1.36 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 162.8, 149.2, 147.0, 139.0, 128.6, 128.5, 127.8, 127.3,
123.8, 122.3, 83.3, 61.1, 44.4, 27.6. HRMS (ESI) calcd for C19H21N2O (M+H)+ m/z 293.1654, found m/z
293.1652.
3-Benzyl-4,4-dimethyl-5-nonylidene-1-phenylimidazolidin-2-one (2h)
Compound 2h was obtained from 1h in 16 hours, according to the general procedure. The crude was
purified by flash column chromatography using hexane/ethyl acetate (7:3) as eluent to give a mixture of
E and Z (150 mg, 83%) in ca. 1 : 0.06 molar ratio. The major Z isomer characterized as follows: 1H NMR
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(400 MHz, CDCl3) δ 7.45–7.40 (m, 4H), 7.38–7.30 (m, 5H), 7.30–7.26 (m, 1H), 4.54 (s, 2H), 4.34 (t, J =
7.3 Hz, 1H), 1.47–1.41 (m, 2H), 1.35 (s, 6H), 1.32–1.27 (m, 2H), 1.25–1.04 (m, 10H), 0.91 (t, J = 7.1 Hz,
3H). 13C{1H} NMR (101 MHz, CDCl3) δ 157.4, 143.3, 139.6, 138.1, 128.7, 128.5, 127.9, 127.7, 127.2,
126.9, 99.4, 61.1, 43.4, 31.9, 30.0, 29.3, 29.2, 29.0, 27.9, 26.1, 22.7, 14.1.HRMS (ESI) calcd for
C27H37N2O (M+H)+ m/z 405.2906, found m/z 405.2904.
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5-Benzylidene-4,4-dimethyl-1-phenylimidazolidin-2-one (2i)
Compound 2i was obtained from 1i in 16 hours, according to the general procedure. The crude was
purified by flash column chromatography using hexane/ethyl acetate (1:1) as eluent to give two fractions,
one containing the pure 2i Z isomer (62 mg), the other containing a mixture of E and Z (35 mg, see 1H
NMR spectrum of the mixture in SI). The overall yield of Z and E isomers of 2i amounted at 87% (97
mg) with Z/E isomers in 1:0.25 molar ratio. The major isomer Z was isolated as yellowish solid (m.p.
from hexane: 216.5–217.8 °C) and characterized as follow: 1H NMR (400 MHz, CDCl3) δ 7.06–6.95 (m,
5H), 6.88–6.80 (m, 3H), 6.68 (dd, J = 7.2, 1.9 Hz, 2H), 5.81 (bs, 1H), 5.59 (s, 1H), 1.57 (s, 6H). 13C{1H}
NMR (101 MHz, CDCl3) δ 157.8, 145.0, 135.9, 134.6, 128.3, 128.1, 127.0, 126.2, 126.1, 125.2, 99.0,
57.6, 30.1. HRMS (ESI) calcd for C18H19N2O (M+H)+ m/z 279.1497, found m/z 279.1498.
4,4-Dimethyl-1-phenyl-5-(4-(trifluoromethyl)benzylidene)imidazolidin-2-one (2j)
Compound 2j was obtained from 1j in 4 hours, according to the general procedure. The crude was purified
by flash column chromatography using hexane/ethyl acetate (1:1) as eluent to give two fractions, one
containing the pure 2j Z isomer (85 mg), the other containing a mixture of E and Z (43 mg, see 1H NMR
spectrum of the mixture in SI). The overall yield of Z and E isomers of 2j amounted at 93% (128 mg)
with Z/E isomers in 1:0.3 molar ratio. The major isomer Z was isolated as white solid (m.p. from hexane:
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208.5–211.4 °C) and characterized as follow: H NMR (400 MHz, CDCl3) δ 7.54–7.47 (m, 4H), 7.41–
7.34 (m, 3H), 7.29 (d, J = 8.6 Hz, 2H), 5.61 (s, 1H), 5.49 (bs, 1H), 1.42 (s, 6H). 13C{1H} NMR (101 MHz,
CDCl3) δ 156.7, 149.5, 140.1 (q, JC,F = 0.9 Hz),134.9, 130.3, 129.8, 128.6 (q, JC,F = 29.5 Hz), 128.5,
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128.3, 125.0 (q, JC,F = 3.8 Hz), 124.3 (q, JC,F = 271.8 Hz), 99.9, 57.8, 29.2. F{1H} NMR (376 MHz,
CDCl3) δ -62.44. HRMS (ESI) calcd for C19H18F3N2O (M+H)+ m/z 347.1371, found m/z 347.1369.
5-(4-Methoxybenzylidene)-4,4-dimethyl-1-phenylimidazolidin-2-one (2k)
Compound 2k was obtained from 1k in 16 hours, according to the general procedure. The crude was
purified by flash column chromatography using hexane/ethyl acetate (1:1) as eluent to give two fractions,
one containing the pure 2k Z isomer (32 mg), the other containing a mixture of E and Z (71 mg, see 1H
NMR spectrum of the mixture in SI). The overall yield of Z and E isomers of 2k amounted at 84% (103
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mg) with Z/E isomers in 1:0.04 molar ratio. The major isomer Z was isolated as white solid (m.p. from
hexane: 182.4–184.7 °C) and characterized as follow: 1H NMR (400 MHz, CDCl3) δ 7.08–6.96 (m, 5H),
6.59 (d, J = 8.7 Hz, 2H), 6.39 (d, J = 8.7 Hz, 2H), 5.92 (bs, 1H), 5.54 (s, 1H), 3.65 (s, 3H), 1.55 (s, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 157.9, 157.3, 143.9, 135.9, 129.3, 128.0, 127.2, 126.1, 126.0, 112.6,
98.7, 57.5, 55.3, 30.1. HRMS (ESI) calcd for C19H21N2O2 (M+H)+ m/z 309.1603, found m/z 309.1607.
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4,4-Dimethyl-1-phenyl-5-(thiophen-2-ylmethylene)imidazolidin-2-one (2l)
Compound 2l was obtained from 1l in 1 hour and 30 minutes, according to the general procedure. The
crude was purified by flash column chromatography using hexane/ethyl acetate (1:1) as eluent to give a
mixture of E and Z (110 mg, 97%) in 1 : 0.8 molar ratio. E and Z isomers were characterized as follow:
1H NMR (400 MHz, CDCl3) δ 7.51–7.46 (m, 1H(Z)+1H(E)), 7.43–7.31 (m, 3H), 7.19–7.06 (m, 6H), 6.96–
6.85 (m, 1H(Z)+1H(E)), 6.77 (d, J = 3.4 Hz, 1H), 6.48 (dd, J = 5.0, 3.7 Hz, 1H), 6.13 (bs, 1H), 6.01 (bs,
1H), 5.98 (d, J = 3.5 Hz, 1H), 5.57 (s, 1H(E)), 5.51 (s, 1H(Z)), 1.57 (s, 6H(Z)), 1.55 (s, 6H(E)). 13C{1H}
NMR (101 MHz, CDCl3) δ 157.6, 156.8, 150.1, 145.6, 137.5, 136.8, 135.7, 134.9, 129.7, 128.7, 128.2,
127.3, 126.8, 126.6, 126.5, 126.5, 126.3, 124.8, 123.8, 93.1, 91.5, 57.9, 57.7, 29.9, 28.4. HRMS (ESI)
calcd for C16H17N2OS (M+H)+ m/z 285.1061, found m/z 285.1063.
3-(2-Methylbut-3-yn-2-yl)imidazolidine-2,4-dione (2m’)
Compound 2m’ was obtained from 1m in 16 hours at 50 °C, according to the general procedure. The
crude was purified by flash column chromatography using hexane/ethyl acetate (1:1) as eluent to give
2m’ (48 mg, 72% yield) as white solid; m.p. (hexane) 81.1–82.6 °C. 1H NMR (400 MHz, CDCl3) δ 6.33
(bs, 1H), 3.88 (d, J = 1.2 Hz, 2H), 2.47 (s, 1H), 1.89 (s, 6H). 13C{1H} NMR (101 MHz, CDCl3) δ 170.9,
158.1, 85.5, 71.2, 52.3, 46.2, 29.0. HRMS (ESI) calcd for C8H11N2O2 (M+H)+ m/z 167.0820, found m/z
167.0817.
(Z)-N-(4,4-dimethyl-5-methylenethiazolidin-2-ylidene)-4-fluoroaniline (2n’)
Compound 2n’ was synthesized as reported above, in the absence of catalyst.25 Expected acyclic thiourea
1i was not detected and (Z)-N-(4,4-dimethyl-5-methylenethiazolidin-2-ylidene)-4-fluoroaniline (2n’) was
instead isolated. Product 2n’ was recovered without purification in 98% yield (1 mmol, 231 mg) as yellow
solid; m.p. (hexane) 223.3–224.6 °C. 1H NMR (400 MHz, DMSO-d6, recorded at 80 °C) δ 8.73 (bs, 1H),
7.54–7.32 (m, 2H), 7.16–6.88 (m, 2H), 5.21 (d, J = 1.4 Hz, 1H), 5.14 (d, J = 1.4 Hz, 1H), 1.42 (s, 6H).
13C{1H} NMR (101 MHz, DMSO-d6, recorded at 80 °C) δ 157.0 (d, JC,F = 238.3 Hz), 154.7, 149.5, 139.
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8, 120.0 (d, JC,F = 7.1 Hz), 114.6 (d, JC,F = 22.2 Hz), 101.6, 74.4, 29.5. F{1H} NMR (376 MHz, DMSO-
d6) δ -121.82. HRMS (ESI) calcd for C12H13FN2NaS (M+Na)+ m/z 259.0681, found m/z 259.0683.
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1,4-Dibenzyl-3,5-diphenyl-1H-imidazol-2(3H)-one (4a)
Compound 4a was obtained from 3a in 1 minute, according to the general procedure. The crude was
purified by flash column chromatography using hexane/ethyl acetate (6:4) as eluent to give 4a (139 mg,
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83% yield) as pale yellow oil. The spectroscopic data of 4a were consistent with literature values.8a 1
H
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NMR (400 MHz, CDCl3) δ 7.43–7.36 (m, 3H), 7.35–7.23 (m, 8H), 7.20–7.15 (m, 2H), 7.14–7.08 (m, 5H),
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6.81–6.72 (m, 2H), 4.92 (s, 2H), 3.71 (s, 2H). C{1H} NMR (75 MHz, CDCl3) δ 153.6, 138.2, 137.9,
135.2, 130.4, 129.1, 129.0, 128.7, 128.6, 128.5, 128.2, 128.1, 128.0, 127.8, 127.8, 127.3, 126.3, 122.3,
119.1, 45.5, 29.8. HRMS (ESI) calcd for C29H25N2O (M+H)+ m/z 417.1967, found m/z 417.1970.
1-Benzyl-4-nonyl-3,5-diphenyl-1H-imidazol-2(3H)-one (4b)
Compound 4b was obtained from 3b in 1 minute, according to the general procedure. After 16 hours yield
of 4b did not improve and most of the starting material was recovered (70%). The crude was purified by
flash column chromatography using hexane/ethyl acetate (7:3) as eluent to give 4b (33 mg, 18% yield) as
pale orange oil. 1H NMR (400 MHz, CDCl3) δ 7.50–7.45 (m, 2H), 7.42–7.40 (m, 1H), 7.40–7.38 (m, 1H),
7.38–7.34 (m, 4H), 7.23–7.15 (m, 5H), 7.06–7.02 (m, 2H), 4.81 (s, 2H), 2.35–2.31 (m, 2H), 1.27–0.90
(m, 14H), 0.85 (t, J = 7.2 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 153.5, 138.0, 135.7, 130.6, 129.5,
129.3, 128.6, 128.4, 128.4, 127.9, 127.8 (2C), 127.3, 121.1, 120.8, 45.4, 31.9, 29.3, 29.2, 28.9, 28.7, 28.4,
23.5, 22.7, 14.2. HRMS (ESI) calcd for C31H37N2O (M+H)+ m/z 453.2906, found m/z 453.2902.
4-Benzyl-1-butyl-3,5-diphenyl-1H-imidazol-2(3H)-one (4c)
Compound 4c was obtained from 3c in 1 minute, according to the general procedure. The crude was
purified by flash column chromatography using hexane/ethyl acetate (7:3) as eluent to give 4c (108 mg,
71% yield) as white solid; m.p. (hexane) 112.6–113.7 °C. 1H NMR (400 MHz, CDCl3) δ 7.48–7.36 (m,
5H), 7.31–7.23 (m, 3H), 7.14–7.05 (m, 5H), 6.73 (dd, J = 6.6, 2.8 Hz, 2H), 3.75–3.70 (m, 2H), 3.68 (s,
2H), 1.56–1.47 (m, 2H), 1.28–1.17 (m, 2H), 0.81 (t, J = 7.4 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3)
δ 153.2, 138.3, 135.2, 130.0, 129.4, 128.9, 128.8, 128.5, 128.2, 128.0, 127.9, 127.7, 126.2, 122.2, 118.7,
41.5, 31.3, 29.7, 19.8, 13.6. HRMS (ESI) calcd for C26H27N2O(M+H)+ m/z 383.2123, found m/z 383.2126.
4-Benzyl-3,5-diphenyl-1-(1-phenylethyl)-1H-imidazol-2(3H)-one (4d)
Compound 4d was obtained from 3d in 1 minute, according to the general procedure. The crude was
purified by flash column chromatography using hexane/ethyl acetate (6:4) as eluent to give 4d (160 mg,
93% yield) as pale orange oil. 1H NMR (400 MHz, CDCl3) δ 7.40–7.35 (m, 3H), 7.35–7.26 (m, 8H), 7.24–
7.20 (m, 2H), 7.15 (dd, J = 7.9, 1.4 Hz, 2H), 7.13–7.08 (m, 3H), 6.74 (dd, J = 6.4, 2.6 Hz, 2H), 5.29 (q, J
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