Facile Electrochemical Intramolecular Amination of Urea-Tethered Terminal Alkenes for the Synthesis of Cyclic Ureas

Article abstract of DOI:10.1002/open.201800064

Facile intramolecular amination of unactivated alkenes has been achieved by using electricity as a catalyst that helps to generate an intermediate and accelerates formation of cyclic ureas in high yields. Using this method, no metal catalysts were used. D

Full text of DOI:10.1002/open.201800064

DOI: 10.1002/open.201800064
Facile Electrochemical Intramolecular Amination of Urea-
Tethered Terminal Alkenes for the Synthesis of Cyclic
Ureas
Nisar Ahmed*[a] and Saira Khatoon[a, b]
Facile intramolecular amination of unactivated alkenes has
been achieved by using electricity as a catalyst that helps to
generate an intermediate and accelerates formation of cyclic
ureas in high yields. Using this method, no metal catalysts
were used. During electrolysis, a nitrogen radical was formed
at the urea substrate that cyclized with the alkene and gener-
ated a terminal carbon radical which further formed a bond
with the 2,2,6,6-tetramethylpiperidine-N-oxyl radical (TEMPO).
This method of electrolysis not only gives cyclic ureas but also
functionalizes terminal unactivated alkenes. This method can
be considered to be environmentally friendly given that it
avoids the issues of toxicity or complicated metal ligands and
could therefore be potentially employed in green chemistry.
1. Introduction
The 1,2-difunctionalization of alkenes with heteroatoms is a
powerful organic transformation to prepare molecules with di-
verse new functionalities.[1] These functionalized hetero mole-
cules can be used further to investigate prominent biological
activities as well as in the synthesis of chiral reagents and natu-
ral products. Vicinal difunctionalization of alkenes and amina-
tion reactions mainly depend on transition metal catalysis, hy-
pervalent iodine reagents and photocatalysis.[2–5] The well-
known Sharpless asymmetric aminohydroxylation and dihy-
droxylation[6] catalysed by osmium metal is a famous route for
difunctionalisation of alkenes and this method has been fol-
lowed several decades. Palladium catalysts have been used for
intramolecular aminations of unfunctionalized alkenes to the
synthesis of bicylic ureas [Eq. (1)].[7] Progress has been made in
the application of expensive Pt[8a] and Ag[8b] catalysts or by
using excess amounts of Lewis acids[9] [Eq. (2)] to synthesize
fused bicyclic isoureas through intramolecular amino-oxylation
of alkenes. In 2015, Shi et al. reported the efficient chemoselec-
tive synthesis of ureas and isoureas in high yields by control-
ling O/N nucleophilic addition in urea-tethered alkenes by
using PhI(OAc)2 as the oxidant in the presence of Pd or Cu cat-
alyst [Eq. (3)].[10] Amination and functionalisation of unactivated
alkenes in synthesis is a continuing challenge. Several reagents
and reagent combinations have been developed for such reac-
tions, but most of them are dependent on oxidants and cata-
lysts. Moreover, electrochemical intramolecular amination of
urea-tethered terminal alkenes has not been reported.[11] How-
ever, a few cyclization reactions have been reported employing
allylcarbamates and amides as the substrates.[11b–f] Xu et al.
have been involved in developing sustainable CÀN bond-form-
ing reactions by employing electrochemically generated nitro-
gen-centered radical (NCR) intermediates. Difunctionalization
of a variety of alkenes with carbamates/amides and TEMPO af-
fords aminooxygenation products in good yields.[11b] Further-
more, they envisioned this approach for electrochemical intra-
molecular oxidative amination reaction of hindered tri- and tet-
rasubstituted alkenes to synthesis alkene-bearing cyclic carba-
mates, ureas and lactams [Eq. (4)].[11a] Wirth et al. developed an
electrochemical flow method for the intramolecular oxidative
amination of alkenes with TEMPO. They have demonstrated
the facile synthesis of amidyl radicals used in intramolecular
hydroaminations to produce isoindolinones.[11c] The electrically
catalysed organic reactions occur at the interface of electrodes
and an electrolyte. These reactions serve as powerful methods
for the synthesis of complex organic molecules as they provide
for an easy generation of highly reactive species, even under
very mild conditions, and can be consequently applied in
green chemistry.[12]
[a] N. Ahmed, S. Khatoon
School of Chemistry
Cardiff University
Cardiff, CF10 3AT (UK)
E-mail: AhmedN14@cardiff.ac.uk
[b] S. Khatoon
Department of Chemistry
Quaid-i-Azam University
Islamabad 45320 (Pakistan)
Supporting Information and the ORCID identification number(s) for the
author(s) of this article can be found under:
Cyclic ureas are heterocyclic motifs frequently observed in
biologically active molecules.[13] They are also involved in im-
portant organic transformations and are important precursors
for the synthesis of vicinal diamines and amino alcohols.[14] De-
spite their extensive utility, the development of a new method
allowing efficient preparation of these heterocycles continues
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608C and a constant current of 10 mA in a three-necked
round-bottom flask equipped with a reticulated vitreous
carbon (RVC) anode and a platinum wire cathode. A solution
of 0.1m Bu4NBF4 in CH3CN/H2O (19:1 v/v) was used as the sup-
porting electrolyte and 1.5 equivalents of TEMPO were includ-
ed. After 1.8 FmolÀ1 of electricity was passed through the elec-
trolysis process, the precursor was consumed and the desired
product 2a was isolated in 83% yield (Scheme 1). 1.1 equiva-
lents of Na2CO3 was used as a base in this reaction.
Scheme 1. Difunctionalization of alkenes. Reaction conditions: 1a
(0.35 mmol), TEMPO (0.53 mmol), H2O (0.5 mL), CH3CN (9.5 mL), 608C. 2a
was isolated in 83% yield.
After setting optimized conditions in electrolysis, the sub-
strate scope was examined on the anodically catalysed difunc-
tionalization of alkenes. The NH-phenyl ring of 1a was modi-
fied with various functional groups to investigate their effects
on alkene difuctionalization. All substrates were synthesized in
high yields (Scheme 2, Figure 1). For their synthesis, allylamine
Scheme 2. Substrates synthesis (1a–j). Reaction conditions: aryl isocyanate
(1.0 equiv), dry CH2Cl2 (25 mL), allylamine (1.1 equiv), 08C to rt, 4 h; yields of
isolated products are given in Figure 1.
to be a stimulating challenge in organic synthesis. Herein, we
have developed an electrochemical method for difunctionalisa-
tion of urea-tethered alkenes and report an economic, environ-
mentally friendly controlled intramolecular amination. This
method allows the construction of cyclic ureas in high yields
from urea nucleophiles [Eq. (5)]. In this electrochemical reac-
tion, the addition of the anodically generated nitrogen radi-
cal[15] to a tethered alkene leads to a new terminal carbon radi-
cal, which is trapped with 2,2,6,6-tetramethylpiperidine-N-oxyl
radical (TEMPO) to afford the final cyclic urea. This electro-
chemical method precludes the use of stoichiometric quanti-
ties of chemical oxidants. The interception of this carbon radi-
cal with a trapping reagent (TEMPO)[1f] would also lead to di-
functionalization of the alkene. Since no second oxidation
would be required in such a situation, the reaction might work
with an unactivated olefin.
(3, 1.1 equiv) was added to a stirred solution of corresponding
aryl isocyanate (4, 1.0 equiv) in dry CH2Cl2 (DCM) at 08C and
then reaction was allowed to warm to room temperature and
stirred for 4 h to obtain the desired urea substrate 1. The sub-
strate bearing functional groups, such as mono- and di-substi-
tuted Me, MeO, CF3, NO2, fluoro and benzyl, could proceed
smoothly in the electrochemical system (see Table 1, 2a–e,
2i,j). The introduction of a tosyl and naphthyl groups, howev-
er, led to dissatisfactory results, which was probably caused by
the decomposition of the product 2 f–h during the electrolysis
(Table 1) or due to the steric hindrance of bulky tosyl and
naphthyl groups which block the addition of TEMPO radical to
form a bond at the terminal carbon radical of alkenes. The
other possible reason could be the failure of 1 f–h to cyclize
due to the difficulty in forming the requisite nitrogen radical.
The possible mechanism for the electrosynthesis was pro-
posed using urea substrate R (Scheme 3). The process origi-
nates from anodic oxidation of TEMPO to oxoammonium ion,
and cathodic reduction of water (H2O) to hydroxide (OHÀ) and
H2. Then deprotonation of substrate R by electrogenerated hy-
2. Result and Discussion
N-allylic urea 1a was used as the first example and submitted
to electrochemical difunctionalization. The reaction was run at
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Figure 1. Substrates scope for the synthesis of urea-tethered alkenes (1a–j).
Scheme 3. Proposed mechanism for alkene difunctionalization.
droxide leads to a nitrogen-containing anion, which is a much
better electron donor than its neutral precursor. Single-electron
transfer (SET) between the nitrogen-containing anion substrate
RÀ and the oxoammonium ion affords the electron-deficient ni-
trogen-centered radical and regenerates the TEMPO radical
molecule. Subsequently, the nitrogen radical intermediate can
cyclize onto the cyclic urea group to give another radical at
the terminal carbon that reacts with the TEMPO radical mole-
cule to form the difunctionalized product P.[11f]
facilitator and in radical trapping. This intramolecular amina-
tion of urea-tethered alkenes represents an environmentally
friendly method that avoid the issues of toxicity or the compli-
cated ligands of many transition-metal-based systems. In this
procedure, catalyst- and oxidant-free conditions are used,
which deserves significant attention from the viewpoint of
green chemistry.
Experimental Section
All the solvent and chemicals were purchased from Sigma Aldrich,
Alfa Aesar, Acros Organic and FluoroChem and were used without
further purification. All air sensitive reactions were carried out
under an argon or nitrogen atmosphere. Thin-layer chromatogra-
phy (TLC) was performed on pre-coated aluminium sheets of
Merck silica gel 60 F254 (0.20 mm) and visualised by UV radiation
(254 nm). Automated column chromatography was performed on
a Biotageꢁ Isolera Four. 1H NMR and 13C NMR spectra were mea-
sured on Bruker DPX 300, 400 or 500 apparatus. Mass spectromet-
ric measurements were performed by the EPSRC Mass Spectrome-
try Facility in Swansea University on a Waters Xevo G2-S and on a
3. Conclusions
In conclusion, this is a facile and green approach to generate a
radical at the nitrogen center without the use of expensive
metal catalysts and by using only electricity, which is economi-
cally excellent. Then this nitrogen radical on addition to unacti-
vated/unsubstituted terminal alkenes in the presence of
TEMPO constitutes a general and mild approach to alkene di-
functionalization and construction of cyclic ureas in high
yields. In this procedure, TEMPO plays the dual role of redox
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and stirred for 4 hours. The reaction mixture was then diluted with
CH2Cl2, washed with water, HCl (1 N), NaHCO3 (sat.) and brine,
dried with anhydrous MgSO4. The mixture was filtered, and the fil-
trate was concentrated under vacuum. The residue was purified
through silica gel flash chromatography (eluents: hexanes and
ethyl acetate).
Table 1. Difunctionalization of alkenes.
General Procedure for the Electrolysis
The substrate (0.35 mmol, 1 equiv), TEMPO (0.53 mmol, 1.5 equiv),
Bu4NBF4 (1.0 mmol), Na2CO3 (0.39 mmol, 1.1 equiv) were placed in
a 25 mL three-necked round-bottom flask equipped with a RVC
anode and a platinum wire cathode. The flask was flushed with
argon. Acetonitrile (9.5 mL) and water (0.5 mL) were added. The re-
sulting mixture was sonicated for 0.5 min. The electrolysis was car-
ried out at 608C and a constant current of 10 mA until complete
consumption of the substrate (monitored by TLC or 1H NMR). The
reaction mixture was cooled to RT. Water (25 mL) and ethyl acetate
(25 mL) were added. The phases were separated and the aqueous
phase was extracted with ethyl acetate (2ꢂ25 mL). The combined
organic solution was dried over anhydrous MgSO4 and concentrat-
ed under reduced pressure. The residue was chromatographed
through silica gel eluting with ethyl acetate/hexanes to give the
product. Automated column chromatography was also performed
on a Biotageꢁ Isolera Four for purification of few products.
1-Allyl-1,3-diphenylurea (1a)
1
White crystalline solid, mp=(110–112)8C; H NMR (300 MHz, CDCl3)
d=7.43–7.00 (m, 10H), 6.84 (t, J=6.8 Hz, 1H), 6.16 (s, 1H), 5.82
(ddt, J=16.4, 10.5, 6.1 Hz, 1H), 5.14–4.90 (m, 2H), 4.21 ppm (d, J=
6.1 Hz, 2H); 13C NMR (101 MHz, Acetone) d=153.93, 142.06,
140.16, 134.93, 129.80, 128.68, 128.36, 128.15, 127.21, 122.11,
119.27, 118.50, 116.22, 52.09 ppm; ESI HRMS m/z: calcd
252.1263 gmolÀ1. Observed 253.1352 gmolÀ1
.
1-Allyl-1-phenyl-3-(4-(trifluoromethyl)phenyl)urea (1b)
White crystalline solid, mp=(116–117)8C; 1H NMR (300 MHz,
DMSO) d=8.56 (s, 1H), 7.70 (d, J=8.7 Hz, 2H), 7.60 (d, J=8.8 Hz,
2H), 7.50–7.39 (m, 2H), 7.31 (ddd, J=8.4, 4.9, 1.6 Hz, 3H), 5.93 (dtd,
J=15.8, 10.6, 5.5 Hz, 1H), 5.29–5.02 (m, 2H), 4.37 ppm (d, J=
5.5 Hz, 2H); 13C NMR (75 MHz, DMSO) d=192.51, 154.51, 144.39,
142.56, 134.95, 129.81, 127.50, 126.82, 125.99, 125.94, 122.55,
122.12, 119.68, 117.10, 52.53 ppm; 19F NMR (376 MHz, Acetone) d=
À62.08 ppm; ESI HRMS m/z [M+H]+calcd 320.1136 gmolÀ1 Ob-
served 321.1210 gmolÀ1
.
Thermo Scientific LTQ Orbitrap XL machine for high-resolution
mass spectroscopy (HRMS). The electrochemical reactions were car-
ried out in a galvanostatic mode using a GWINSTEK GPR-30H10D.
1-Allyl-3-(3,5-bis(trifluoromethyl)phenyl)-1-phenylurea (1c)
White crystalline solid, mp=(128–130)8C; 1H NMR (400 MHz,
DMSO) d=8.83 (s, 1H), 8.28 (s, 2H), 7.64 (s, 1H), 7.54–7.44 (m, 2H),
7.44–7.33 (m, 3H), 6.09–5.73 (m, 1H), 5.24–4.97 (m, 2H), 4.37 ppm
(d, J=5.6 Hz, 2H); 13C NMR (101 MHz, DMSO) d=154.40, 142.76,
141.87, 134.70, 131.16, 130.83, 130.51, 130.19, 129.95, 128.01,
127.36, 125.23, 122.52, 119.70, 117.33, 114.81, 114.77, 52.71 ppm;
19F NMR (376 MHz, Acetone) d=À63.59 ppm; ESI HRMS m/z: calcd
General Procedure for the Preparation of Allyl Ureas
To a stirred solution of an aryl isocyanate (1.0 equiv) in dry CH2Cl2
at 08C under N2, the corresponding allylamine (1.1 equiv) was
added. The reaction was allowed to warm to room temperature
388.1010 gmolÀ1. Observed 389.1108 gmolÀ1
.
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137.84, 135.34, 131.35, 129.76, 129.12, 127.46, 126.53, 120.44,
1-Allyl-3-(4-nitrophenyl)-1-phenylurea (1d)
116.87, 52.29, 20.79 ppm; ESI HRMS m/z [M+H]+ calcd
1
Yellow crystalline solid, mp=(123–125)8C; H NMR (400 MHz, Ace-
266.1419 gmolÀ1. Observed 367.1509 gmolÀ1
.
tone) d=8.00–7.95 (m, 1H), 7.89 (s, 1H), 7.61–7.54 (m, 1H), 7.38–
7.16 (m, 2H), 5.82 (ddt, J=17.2, 10.2, 6.0 Hz, 1H), 4.98 (ddq, J=
13.2, 10.2, 1.5 Hz, 1H), 4.23 ppm (dt, J=6.0, 1.4 Hz, 1H); 13C NMR
(75 MHz, Acetone) d=153.39, 146.67, 141.86, 141.31, 134.29,
129.88, 128.17, 127.61, 124.43, 118.39, 116.62, 52.46 ppm; ESI HRMS
m/z: calcd 297.1113 gmolÀ1. Observed 298.1210 gmolÀ1
1-Allyl-3-(4-methoxyphenyl)-1-phenylurea (1j)
White crystalline solid, mp=(111–112)8C; 1H NMR (500 MHz,
[D6]DMSO) d=7.85 (s, 1H), 7.42–7.23 (m, 7H), 6.82–6.79 (m, 2H),
5.88 (ddd, J=22.6, 10.6, 5.5 Hz, 1H), 5.11 (ddd, J=13.7, 11.4, 1.3 Hz,
2H), 4.31 (d, J=5.5 Hz, 2H) 3.68 ppm (s, 3H); 13C NMR (126 MHz,
[D6]DMSO) d=154.98, 143.07, 135.41, 133.41, 129.74, 127.49,
126.47, 122.31, 116.83, 113.91, 55.59, 52.28 ppm; ESI HRMS m/z
1-Allyl-3-(perfluorophenyl)-1-phenylurea (1e)
White crystalline solid, mp=(72–73)8C; 1H NMR (300 MHz, CDCl3)
d=7.43–7.00 (m, 10H), 6.84 (t, J=6.8 Hz, 1H), 6.16 (s, 1H), 5.82
(ddt, J=16.4, 10.5, 6.1 Hz, 1H), 5.14–4.90 ppm (m, 2H), 4.21 (d, J=
6.1 Hz, 2H); 13C NMR (75 MHz, CDCl3) d=153.34, 140.80, 133.24,
130.37, 128.63, 128.38, 118.12, 77.47, 77.04, 76.62, 52.89 ppm;
19F NMR (376 MHz, DMSO) d=À146.47, À146.52, À146.53,
À160.07, À160.13, À160.19, À164.14, À164.20, À164.25,
À164.26 ppm; ESI HRMS m/z [M+H]+calcd 342.0792 gmolÀ1 Ob-
[M+H]+ calcd 282.1368 gmolÀ1. Observed 283.1452 gmolÀ1
.
1,3-Diphenyl-4-(((2,2,6,6-tetramethylpiperidin-1-yl)oxy)me-
thyl)imidazolidin-2-one (2a)
White crystalline solid, mp=(133.4–134.7)8C; 1H NMR (300 MHz,
DMSO) d=7.66–7.46 (m, 4H), 7.35–7.17 (m, 4H), 7.05–6.83 (m, 2H),
4.84–4.50 (m, 1H), 4.05 (t, J=9.4 Hz, 1H), 3.81 (dd, J=9.7, 3.4 Hz,
1H), 3.73–3.62 (m, 2H), 1.56–0.99 (m, 6H), 0.94 (s, 1H), 0.82 (s, 1H),
0.66 (s, 1H), 0.59 ppm (s, 1H). 13C NMR (75 MHz, DMSO) d=154.88,
140.63, 139.09, 129.18, 128.97, 123.80, 122.69, 121.41, 117.98, 75.55,
59.93, 59.72, 51.60, 45.47, 33.22, 32.54, 19.91, 16.87 ppm. ESI HRMS
served 343.0866 gmolÀ1
.
1-Allyl-3-(naphthalen-2-yl)-1-phenylurea (1 f)
White crystalline solid, mp=(117–118)8C; 1H NMR (400 MHz, Ace-
tone) d=7.93 (d, J=2.0 Hz, 1H), 7.62 (d, J=8.5 Hz, 1H), 7.60–7.56
(m, 2H), 7.40–7.14 (m, 9H), 5.84 (ddt, J=17.2, 10.2, 6.0 Hz, 1H),
5.07–4.86 (m, 2H), 4.24 ppm (dt, J=6.0, 1.4 Hz, 2H); 13C NMR
(101 MHz, Acetone) d=154.02, 142.01, 137.82, 134.89, 134.11,
129.84, 129.82, 128.21, 127.91, 127.40, 127.29, 127.11, 126.08,
123.99, 120.46, 116.28, 114.85, 52.17 ppm; ESI HRMS m/z: calcd
302.1419 gmolÀ1. Observed 303.1493 gmolÀ1
m/z [M+H]+ calcd 407.2573 gmolÀ1 Observed 408.2643 gmolÀ1
.
1-Phenyl-4-(((2,2,6,6-tetramethylpiperidin-1-yl)oxy)methyl)-
3-(4 (trifluoromethyl)phenyl)imidazolidin-2-one (2b)
Off white crystalline solid, mp=(135–138)8C; 1H NMR (300 MHz,
CDCl3) d=7.64 (d, J=8.7 Hz, 2H), 7.56–7.48 (m, 4H), 7.35–7.27 (m,
2H), 7.08–6.99 (m, 1H), 4.61–4.46 (m, 1H), 4.04 (t, J=9.2 Hz, 1H),
3.90 (d, J=5.0 Hz, 2H), 3.79 (dd, J=9.1, 4.3 Hz, 1H), 1.50–1.11 (m,
6H), 1.03 (s, 3H), 0.95 (s, 3H), 0.82 ppm (s, 6H), 13C NMR (75 MHz,
CDCl3) d=154.65, 141.84, 139.61, 130.40, 128.98, 128.49, 125.97,
125.92, 125.47, 125.04, 123.41, 122.44, 120.13, 118.48, 118.34, 75.80,
60.03, 51.37, 45.80, 39.57, 33.02, 32.82, 20.03, 19.86, 16.90 ppm,
19F NMR (376 MHz, Acetone) d=À67.21 ppm. ESI HRMS m/z
N-(Allyl(phenyl)carbamoyl)-4-methylbenzenesulfonamide
(1g)
White crystalline solid, mp=(114–115)8C; 1H NMR (400 MHz, Ace-
tone) d=8.78 (s, 1H), 7.78–7.70 (m, 2H), 7.35–7.08 (m, 7H), 5.76–
5.54 (m, 1H), 5.02–4.78 (m, 2H), 4.04 (dt, J=6.1, 1.4 Hz, 2H),
2.30 ppm (s, 3H); 13C NMR (126 MHz, Acetone) d=150.73, 143.89,
140.53, 137.78, 133.43, 129.72, 129.10, 128.28, 128.26, 127.85,
[M+H]+ calcd 475.2447 gmolÀ1 Observed 476.2525 gmolÀ1
.
117.12, 52.32, 20.65 ppm.; ESI HRMS m/z: calcd 330.1038 gmolÀ1
Observed 331.1118 gmolÀ1
.
3-(3,5-Bis(trifluoromethyl)phenyl)-1-phenyl-4-(((2,2,6,6-tetra-
methylpiperidin-1-yl)oxy)methyl)imidazolidin-2-one (2c)
White crystalline solid, mp=(151–153)8C; 1H NMR (400 MHz,
CDCl3) d=8.05 (s, 2H), 7.60–7.45 (m, 3H), 7.39–7.23 (m, 2H), 7.13–
6.97 (m, 1H), 4.69–4.49 (m, 1H), 4.09 (t, J=9.2 Hz, 1H), 4.01–3.84
(m, 2H), 3.73 (dt, J=14.9, 7.5 Hz, 1H), 1.52–1.20 (m, 6H), 1.01 (s,
3H), 0.94 (s, 3H), 0.86 (s, 3H), 0.72 ppm (s, 3H), 13C NMR (101 MHz,
Acetone) d=154.27, 141.82, 139.99, 131.57, 131.24, 128.71, 125.01,
122.99, 122.30, 120.21, 120.18, 118.07, 115.49, 115.45, 115.41, 76.90,
59.71, 59.59, 51.19, 45.37, 39.46, 39.45, 32.51, 32.16, 19.21, 19.07,
16.65 ppm, 19F NMR (376 MHz, Acetone) d=À68.15 ppm. ESI HRMS
1-(2-Allylphenyl)-3-(1-(naphthalen-1-yl)ethyl)urea (1h)
Off white liquid; 1H NMR (300 MHz, CDCl3) d=8.09 (d, J=8.4 Hz,
1H), 7.75 (d, J=7.8 Hz, 1H), 7.65 (d, J=8.1 Hz, 1H), 7.52–7.35 (m,
2H), 7.34–7.04 (m, 7H), 5.92–5.66 (m, 2H), 5.02 (dd, J=2.9, 1.5 Hz,
1H), 4.97 (dt, J=4.6, 1.4 Hz, 1H), 4.52 (d, J=7.9 Hz, 1H), 4.22 (dt,
J=6.0, 1.3 Hz, 2H), 1.46 ppm (d, J=6.8 Hz, 3H); 13C NMR (75 MHz,
CDCl3) d=155.92, 141.79, 139.63, 134.62, 133.92, 130.99, 129.89,
128.71, 128.23, 127.91, 127.50, 126.28, 125.70, 125.17, 123.65,
122.09, 116.89, 52.32, 46.28, 21.94 ppm.; ESI HRMS m/z: calcd
330.1732 gmolÀ1. Observed 331.1807 gmolÀ1
m/z [M+H]+ calcd 543.2320 gmolÀ1 Observed 544.2419 gmolÀ1
.
3-(4-Nitrophenyl)-1-phenyl-4-(((2,2,6,6-tetramethylpiperidin-
1-yl)oxy)methyl)imidazolidin-2-one (2d)
1-Allyl-1-phenyl-3-(p-tolyl)urea (1i)
White crystalline solid, mp=(113–114)8C; 1H NMR (500 MHz,
[D6]DMSO) d=7.89 (s, 1H), 7.42–7.01 (m, 9H), 5.88 (m, 1H), 5.11
(ddq, J=17.1, 10.3, 1.5 Hz, 2H), 4.31 (dt, J=5.5, 1.4 Hz, 2H),
2.22 ppm (s, 3H); 13C NMR (126 MHz, [D6]DMSO) d=154.80, 143.04,
Yellow crystalline solid, mp=(163.5–167)8C; 1H NMR (300 MHz,
Acetone) d=8.13 (d, J=9.3 Hz, 2H), 7.95 (d, J=9.3 Hz, 2H), 7.61
(d, J=7.9 Hz, 2H), 7.26 (t, J=8.0 Hz, 2H), 6.97 (t, J=7.3 Hz, 1H),
4.88 (d, J=6.3 Hz, 1H), 4.20 (t, J=9.3 Hz, 1H), 4.05 (dd, J=9.9,
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3.3 Hz, 1H), 3.96–3.82 (m, 2H), 1.47–1.09 (m, 6H), 0.99 (s, 3H), 0.88
(s, 3H), 0.69 ppm (s, 6H), 13C NMR (101 MHz, Acetone) d=154.08,
145.84, 142.01, 140.03, 128.72, 124.35, 123.02, 118.76, 118.18, 75.61,
59.80, 59.61, 51.41, 45.44, 39.49, 32.74, 32.13, 29.74, 19.30, 19.23,
16.66, 12.99 ppm. ESI HRMS m/z [M+H]+ calcd 452.2424 gmolÀ1
Keywords: amination
oxidation · TEMPO · terminal alkenes
·
cyclic ureas
·
electrochemical
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Observed 453.2493 gmolÀ1
.
3-(Perfluorophenyl)-1-phenyl-4-(((2,2,6,6-tetramethylpiperi-
din-1-yl)oxy)methyl)imidazolidin-2-one (2e)
White crystalline solid, mp=(118–120)8C; 1H NMR (300 MHz, Ace-
tone) d=7.57–7.50 (m, 2H), 7.28–7.19 (m, 2H), 7.00–6.91 (m, 1H),
4.68–4.51 (m, 1H), 4.20 (t, J=9.5 Hz, 1H), 4.05–3.95 (m, 1H), 3.88
(dd, J=10.3, 3.3 Hz, 1H), 3.66 (dd, J=9.4, 7.1 Hz, 1H), 1.34–1.07 (m,
6H), 0.96 (s, 3H), 0.92 (s, 3H), 0.77 (s, 3H), 0.57 ppm (s, 3H),
13C NMR (75 MHz, Acetone) d=153.96, 139.94, 128.74, 122.89,
117.52, 79.52, 59.57, 59.54, 53.12, 45.43, 39.41, 39.32, 32.59, 32.24,
26.63, 18.87, 18.70, 16.66 ppm, 19F NMR (376 MHz, Acetone) d=
À143.50 (d, J=17.8 Hz), À147.06 (d, J=13.8 Hz), À159.14 (t, J=
21.0 Hz), À165.54 (s), À165.98 (s). ESI HRMS m/z [M+H]+ calcd
497.2102 gmolÀ1 Observed 498.2195 gmolÀ1
.
1-Phenyl-4-(((2,2,6,6-tetramethylpiperidin-1-yl)oxy)methyl)-
3-(p-tolyl)imidazolidin-2-one (2i)
White crystalline solid, mp=(137–138)8C; 1H NMR (500 MHz,
DMSO) d=7.42–7.26 (m, 9H), 4.60–4.58 (m, 1H), 4.09 (t, J=7.5 Hz,
1H), 3.93 (m, 2H) 3.75 (dt, J=13.3, 6.5 Hz, 1H), 2.22 (s, 3H, CH3),
1.30 (m, 6H), 1.03 (s, 3H), 0.95 (s, 3H), 0.82 ppm (s, 6H). 13C NMR
(126 MHz, DMSO) d=155.11, 140.73, 138.89, 129.44, 123.90, 122.78,
121.27, 117.60, 75.80, 59.72, 51.60, 45.32, 33.59, 32.19, 21.49,
20.34,17.08 ppm. ESI HRMS m/z [M+H]+ calcd 421.2729 gmolÀ1
Observed 422.2813 gmolÀ1
.
3-(4-Methoxyphenyl)-1-phenyl-4-(((2,2,6,6-tetramethylpiperi-
din-1-yl)oxy)methyl)imidazolidin-2-one (2j)
White crystalline solid, mp=(128–129)8C; 1H NMR (500 MHz,
DMSO) d=7.41–7.28 (m, 7H), 6.82–6.80 (m, 2H), 4.54 (m, 1H), 4.04
(t, J=9.1 Hz, 1H), 3.91 (d, J=5.6 Hz, 2H), 3.80 (dd, J=9.2, 3.6 Hz,
1H), 3.70 (s, 3H, OCH3) 1.31 (m, 6H), 1.03 (s, 3H), 0.95 (s, 3H),
0.82 ppm (s, 6H). 13C NMR (126 MHz, DMSO) d=154.29, 140.43,
138.89, 129.72, 129.44, 123.51, 122.78, 120.54, 118.41, 76.50, 59.99,
55.61, 51.24, 45.32, 33.22, 32.19, 19.63, 16.38 ppm. ESI HRMS m/z
[M+H]+ calcd 437.2678 gmolÀ1 Observed 438.2757 gmolÀ1
.
Acknowledgements
Marie Skłodowska-Curie Actions COFUND (Grant No 663830) to
N.A. gratefully acknowledged. We thank the Cardiff Chemistry
and Welsh Govt for their generous funding to COFUND Fellow
(N.A). We thank the Prof. Thomas Wirth from Cardiff School of
Chemistry for his continuous technical support. We thank the
Higher Education Commission (HEC) Pakistan for IRSIP Fellowship
to S.K. We also thank to Aggeliki Vgenopoulou (Erasmus student
from Greece) for technical support.
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Conflict of Interest
The authors declare no conflict of interest.
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Received: April 18, 2018
Revised manuscript received: June 5, 2018
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FULL PAPERS
N. Ahmed,* S. Khatoon
Go green: Several reagents and reagent
combinations have been developed for
the amination and functionalisation of
unactivated alkenes. However, most of
these are dependent on oxidants and
catalysts. Herein, we report a green ap-
proach for the intramolecular amination
of urea-tethered alkenes by generating
radicals without using expensive cata-
lysts and employing only electricity.
&& – &&
Facile Electrochemical Intramolecular
Amination of Urea-Tethered Terminal
Alkenes for the Synthesis of Cyclic
Ureas
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