A solvent-free method for substituted imidazolidin-4-ones synthesis

Article abstract of DOI:10.3987/com-03-9997

A new method of the solvent-free synthesis of substituted imidazolidin-4-ones is described. The method is developed for microwave-assisted solvent-free conditions and compared with classical thermally initiated solvent-free conditions. In both cases the reaction proceeds with good yields. However, the reaction under microwave conditions is accelerated six-times. Thermal effect of the microwaves is observed.

Full text of DOI:10.3987/com-03-9997

HETEROCYCLES, Vol. 63, No. 5, 2004, pp. 1165 - 1173
Received, 24th December, 2003, Accepted, 16th February, 2004, Published online, 24th February, 2004
A SOLVENT-FREE METHOD FOR SUBSTITUTED IMIDAZOLIDIN-4-
ONES SYNTHESIS
Jiří Pospíšil and Milan Potáček*
Department of Organic Chemistry, Faculty of Science, Masaryk University,
Kotlářská 2, CZ-611 37 Brno, Czech Republic, e-mail: potacek@chemi.muni.cz
Abstract – A new method of the solvent-free synthesis of substituted
imidazolidin-4-ones is described. The method is developed for microwave-assisted
solvent-free conditions and compared with classical thermally initiated
solvent-free conditions. In both cases the reaction proceeds with good yields.
However, the reaction under microwave conditions is accelerated six-times.
Thermal effect of the microwaves is observed.
Application of syntheses under solvent-free conditions belongs to one of the fast growing application in
organic synthesis.1 Higher environmental safety of such reactions as well as improvement of economy are
reflected in importance of these syntheses.
In our paper, we have focused on synthesis of substituted imidazolidin-4-ones (3). Such compounds are a
versatile synthons for syntheses of α-amino acids2 and di- or tripeptides.3 The most known skeleton
containing imidazolidin-4-one motive is Seebach’s reagent.4
Already published reactions leading to imidazolidin-4-ones (3) are carried out in different solvents
(generally CH2Cl2) and proceed usually within 1 and 11 h. The yields of the reactions vary from moderate
to good.5,6 Here, a new developed procedure of a simple, rapid and one-pot method for a conversion of
N-substituted α-amino acid amides (2) and aldehyde (1) into corresponding imidazolidin-4-one (3) at
solvent-free conditions is described (Scheme 1). The desired imidazolidin-4-ones (3) are under our reaction
conditions formed in good yields (Table).
Two different procedures under solvent-free conditions are found and compared. In the case of a classical
heating the yield of the reaction within 30 min always exceeded 90% .
Microwave irradiation was used as an alternative way of heating. Microwave irradiation (noted as MW)
employing commercially available equipment (PROLABO 402 Synthewave oven) was used. Under these
conditions the reactions with the comparable yields end in 5 min (reaction is six-time faster). The only

one exception was reaction with p-nitrobenzaldehyde. In that case the yield was only 68%. In this case the
reaction product was accompanied with products of decomposition.
R2
R2
HN
O
200oC, 30 min
O
N
R3
R1
+
R1
H
N
H
N
R3
or MW, 5 min
O
1
2
3
Scheme 1
Yield (%)
Compound
R1
R2
R3
Classical
heating
94
Microwaves
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
C6H5
p-Cl-C6H4
p-(CH3)2N-C6H4
p-NO2-C6H4
PhCH2 CH2=CHCH2
PhCH2 CH2=CHCH2
PhCH2 CH2=CHCH2
PhCH2 CH2=CHCH2
89
90
95
68
85
90
94
90
93
89
93
89
91
86
96
95
89
a
o-(CH2=CHCH2O)C6H4 PhCH2 CH2=CHCH2
p-Cl-C6H4
p-(CH3)2N-C6H4
H
PhCH2
PhCH2
PhCH2 CH2=CHCH2
PhCH2 CH2=CHCH2
Me
Me
Me
Me
Me
PhCH2
PhCH2
92
a
92
a
(CH3)2CH
p-Cl-C6H4
p-Cl-C6H4
(CH3)2CH
Me
a
cyclo-C6H11
(CH3)2CH
cyclo-C6H11
(CH3)2CH
93
a
a
Me
cyclo-C6H11
91
a Reaction has not been carried out
Table 1
We suppose that the reaction acceleration is caused by the different transfer of the heat by microwaves. The
reaction mixture is in that case heated up directly inside of the flask.7 On the contrary, during the classical
heating the heat is transferred from the outer medium (oil bath). Of course, the second type of heating must
be slower. It was found during our experiments carried out at oil bath. It takes from 5 to 6 min before the
internal temperature of the sample reaches 200°C. However, in the case of microwave assisted reactions it
takes from 1 to 1.5 min only. We assume that this observed acceleration of the reaction is due to a
microwave action and formation of hot spots in the reaction mixture.

We have found that the method is suitable for all alkyl as well as aryl aldehydes (1). Moreover, desired
substituents R2 and R3 on compounds (2) could be easily introduced by the reaction of α-bromoacetyl
bromide in two steps.8
In conclusion, a new procedure leading to 1,2,3-trisubstituted imidazolidin-4-ones (3) under solvent-free
conditions in good yields was discovered. It was found that this method can be carried out under both
classical and microwave heating. In case of the microwave irradiation acceleration of the reaction was
observed. A rapid internal heating of the sample and hot spots are probably a motor of the acceleration of
the reaction carried out under microwave conditions.
EXPERIMENTAL
Melting points were measured on a Kofler hot stage VEB Wägetechnik Rapido 79/2106. IR spectra were
recorded on a FTIR ATI MATTSON spectrophotometer in NaCl cell or KBr pallets. Microwave
irradiation was carried out in PROLABO 402 Synthewave oven (power 300W, frequency 2450 MHz).
NMR spectra were recorded on Bruker Avance 300 apparatus with working frequency 300 MHz for 1H
and 75 MHz for 13C in CDCl3 with TMS as an internal standard. Chemical shifts are given in ppm,
coupling constants J in Hz. MS were recorded on a FISONS INSTRUMENTS TRIO 1000 spectrometer
in positive mode with electron-ionization (70eV). Flash column chromatography was carried out on
Merck silica (63-100 µm) using petroleum ether:ethyl acetate mixture (ratio is given in procedure).
General procedure for preparation of compounds (2)8
Primary amine (4.0 mmol) was dissolved in dry acetonitrile (2 mL) and the solution was cooled to 0oC. 2-
Bromoacetic acid amide (1.0 mmol) was slowly added to vigorously stirred reaction mixture. The
temperature was kept bellow 10oC during the addition. Then reaction mixture was allowed to warm up to
rt and stirred for additional 4 h. The solvent was removed under vacuum and the residue was dissolved in
2M NaOH (2 mL). Aqueous solution was extracted with Et2O (3x3 mL). Organic layer was dried over
MgSO4 and the solvent together with an excess of primary amine was evaporated under vacuum. Final
product was usually sufficiently pure for following synthesis.
General procedure for preparation of compounds (3)
A mixture of aldehyde (1) (1.0 mmol) and amine (2) (1.0 mmol) was irradiated by microwaves for 5
minutes. Temperature of the reaction mixture was maintained at 200 °C. Then the reaction mixture was
allowed to cool down to rt and crude reaction mixture was purified by flash column chromatography.
For a comparison the reaction mixture of the same composition was placed into preheated oil bath.
Temperature of the oil bath was maintained at 200°C. Temperature of the reaction mixture reached 200oC

in 5 minutes after the reaction started (measured by optical fiber directly inside the reaction mixture).
After 30 minutes the reaction mixture was allowed to cool down to rt and crude reaction mixture was
separated by flash column chromatography.
3-Allyl-1-benzyl-2-phenylimidazolidin-4-one (3a): Flash chromatography (1:3) − Slightly yellow
crystals, mp 62-63oC (petroleum ether/ethyl acetate). IR (KBr): ν-1 = 3081 (w), 3064 (w),
Ph
9
3029 (w), 2921 (w), 2850 (w), 2800 (w), 1708 (s), 1432 (m), 1414 (m), 1371 (w),
1103 (w), 1025 (w), 700 (m). 1H NMR (300 MHz): δ 3.05 (dd, 1H, 2J6,6=15.3, 3J6,7=7.3
Hz, one of H-6), 3.18 (dd, 1H, 2J5a,5b=14.6, 5J5a,6=2.0 Hz, H-5a), 3.45 (d, 1H, 2J9,9=13.2
H5a
H2
R
N1
5
4
H5b
2
N3
O
H8b
6
2
2
Hz, one of H-9), 3.60 (d, 1H, J5b,5a=14.5 Hz, H-5b), 3.83 (d, 1H, J9,9=13.2 Hz, the
7
8
H8a
2
3
5
other of H-9), 4.23 (ddd, 1H, J6,6=15.4, J6,7=4.6, J6,5a=1.9 Hz, the other of H-6), 4.96
(dd, 1H, 3J8b,7=17.2, 2J8b,8a=1.3 Hz, H-8b), 5.01 (s, 1H, H-2), 5.10 (dd, 1H, 3J8a,7=10.2, 2J8a,8b=1.3 Hz, H-8a),
5.60 (m, 1H, H-7), 7.21–7.48 (m, 10H, arom. CH). 13C NMR (75 MHz): δ 42.8 (C-6), 54.9 (C-5), 56.4
(C-9), 81.6 (C-2), 118.4 (C-8), 127.7–146.2 (arom. CH and Cq), 132.1 (C-7), 170.8 (C-4, C=O). EI-MS;
m/z (%): 293.5 (1) [M++1], 292.5 (8) [M+], 291.3 (19), 216.5 (7), 215.2 (74), 201.1 (12), 117.6 (18), 117.6
(18), 91.0 (100), 64.9 (10), 40.8 (9). Anal. Calcd for C19H20N2O: C 78.05 H 6.89 N 9.58. Found C
78.01 H 6.93 N 9.52.
3-Allyl-1-benzyl-2-(4-chlorophenyl)imidazolidin-4-one (3b): Flash chromatography (1:1) – Slightly red
crystals, mp 71-72o C (petroleum ether/ethyl acetate). IR (KBr): ν-1 = 3064 (w), 3027 (w), 2923 (w),
2848 (w), 2807 (w), 1708 (s), 1419 (w), 1292 (m), 1082 (m), 644 (m), 584 (m). 1H NMR (300 MHz): δ
2.91 (dd, 1H, 2J6,6=15.5, 3J6,7=7.6 Hz, one of H-6), 3.04 (dd, 1H, 2J5a,5b=14.4, 5J5a,6=2.0 Hz, H-5a), 3.43
2
2
2
(d, 1H, J9,9=13.2 Hz, one of H-9), 3.47 (d, 1H, J5b,5a=14.5 Hz, H-5b), 3.68 (d, 1H, J9,9=13.2 Hz, the
other of H-9), 4.10 (ddd, 1H, 2J6,6=15.5, 3J6,7=4.6, 5J6,5a=1.7 Hz, the other of H-6), 4.83 (s, 1H, H-2), 4.84
3
2
3
2
(dd, 1H, J8b,7=16.2, J8b,8a=0.9 Hz, H-8b), 4.99 (dd, 1H, J8a,7=10.2, J8a,8b=0.7 Hz, H-8a), 5.47 (m, 1H,
H-7), 7.05–7.38 (m, 9H, arom. CH). 13C NMR (75 MHz): δ 42.7 (C-6), 54.9 (C-5), 56.4 (C-9), 80.9
(C-2), 118.5 (C-8), 127.7–137.2 (arom. CH and Cq), 132.0 (C-7), 170.7 (C-4, C=O). EI-MS; m/z (%): 328.4
(4) [M++1], 326.5 (12) [M+], 325.5 (17), 235.1 (18), 215.2 (61), 178.2 (12), 124.9 (19), 92.0 (11), 90.9
(100), 88.9 (12), 64.9 (8), 40.9 (15). Anal. Calcd for C19H19N2OCl: C 69.83 H 5.86 N 10.85. Found C
69.78 H 5.88 N 10.84.
3-Allyl-1-benzyl-2-[4-(N,N-dimethylamino)phenyl]imidazolidin-4-one (3c): Flash chromatography
(1:3) – White crystals, mp 84-86o C (petroleum ether/ethyl acetate). IR (KBr): ν-1 = 3079 (w), 3027 (w),
2922 (m), 2852 (w), 2802 (w), 1707 (s), 1612 (m), 1434 (m), 1415 (m), 1164 (m), 1120 (m), 808 (w), 700

(w). 1H NMR (300 MHz): δ 3.00 (s, 6H, N(CH3)2), 3.09 (dd, 1H, 2J6,6=15.5, 3J6,7=7.3 Hz, one of H-6),
2
5
2
3.11 (dd, 1H, J5a,5b=14.5, J5a,6=2.1 Hz, H-5a), 3.37 (d, 1H, J9,9=13.2 Hz, one of H-9), 3.54 (d, 1H,
2
2
3
2J5b,5a=14.5 Hz, H-5b), 3.86 (d, 1H, J9,9=13.2 Hz, the other of H-9), 4.20 (ddd, 1H, J6,6=15.5, J6,7=4.7,
5J6,5a=1.9 Hz, the other of H-6), 4.90 (s, 1H, H-2), 5.00 (dd, 1H, 3J8b,7=16.8, 2J8b,8a=0.9 Hz, H-8b), 5.10
(dd, 1H, 3J8a,7=9.9, 2J8a,8b=0.7 Hz, H-8a), 5.63 (m, 1H, H-7), 6.72–7.36 (m, 9H, arom. CH). 13C NMR (75
MHz): δ 40.6 (N(CH3)2), 42.6 (C-6), 55.1 (C-5), 56.1 (C-9), 81.6 (C-2), 112.2–137.2 (arom. CH and Cq),
118.0 (C-8), 132.4 (C-7), 170.8 (C-4, C=O). EI-MS; m/z (%): 335.5 (1) [M+], 293.5 (3), 292.5 (8), 291.3
(17), 216.5 (11), 215.2 (88), 201.0 (17), 117.6 (13), 92.1 (6), 90.9 (100), 64.8 (8), 40.8 (9). Anal. Calcd
for C21H25N3O: C 75.19 H 7.51 N 12.53. Found C 75.11 H 7.48 N 12.50.
3-Allyl-1-benzyl-2-(4-nitrophenyl)imidazolidin-4-one (3d): Flash chromatography (1:1) – White
crystals, mp 93-94o C (petroleum ether/ethyl acetate). IR (KBr): ν-1 = 3080 (w), 3064 (w), 3029 (w), 2924
(w), 2811 (w), 1711 (s), 1524 (s), 1434 (m), 1348 (s), 1315 (m), 801 (m), 701 (m). 1H NMR (300 MHz):
δ 3.04 (dd, 1H, 2J6,6=15.5, 3J6,7=7.6 Hz, one of H-6), 3.26 (dd, 1H, 2J5a,5b=14.5, 5J5a,6=2.0 Hz, H-5a), 3.58
2
2
2
(d, 1H, J9,9=13.2 Hz, one of H-9), 3.69 (d, 1H, J5b,5a=14.5 Hz, H-5b), 3.81 (d, 1H, J9,9=13.2 Hz, the
2
3
5
other of H-9), 4.29 (ddd, 1H, J6,6=15.5, J6,7=4.6, J6,5a=1.7 Hz, the other of H-6), 4.96 (dd, 1H,
3J8b,7=17.2, 2J8b,8a=0.8 Hz, H-8b), 5.11 (s, 1H, H-2), 5.15 (dd, 1H, 3J8a,7=10.2, 2J8a,8b=0.7 Hz, H-8a), 5.62
(m, 1H, H-7), 7.17–8.28 (m, 9H, arom. CH). 13C NMR (75 MHz): δ 42.9 (C-6), 55.0 (C-5), 57.0 (C-9),
80.6 (C-2), 119.0 (C-8), 124.0–145.0 (arom. CH and Cq), 131.8 (C-7), 170.6 (C-4, C=O). EI-MS; m/z
(%): 337.4 (1) [M+], 291.5 (41), 263.2 (6), 216.3 (9), 215.1 (100), 201.1 (15), 118.0 (12), 90.9 (84), 64.8
(7), 40.9 (11). Anal. Calcd for C19H19N3O3: C 67.64 H 5.68 N 12.46. Found C 67.44 H 5.59 N 12.32.
3-Allyl-2-(2-allyoxyphenyl)-1-benzylimidazolidin-4-one (3e): Flash chromatography (1:3) – Slightly
yellow oil. IR (NaCl): ν-1 = 3079 (w), 3066 (w), 3029 (w), 2919 (w), 2852 (w), 2804 (w), 1707 (s), 1598
1
(w), 1490 (m), 1434 (m), 1284 (w), 1240 (m), 1097 (w), 1020 (w), 755 (m), 700 (m). H NMR (300
2
3
2
5
MHz): δ 3.24 (dd, 1H, J6,6=15.5, J6,7=7.8 Hz, one of H-6), 3.22 (dd, 1H, J5a,5b=14.5, J5a,6=1.7 Hz,
H-5a), 3.56 (d, 1H, 2J9,9=13.2 Hz, one of H-9), 3.63 (d, 1H, 2J5b,5a=14.5 Hz, H-5b), 3.87 (d, 1H, 2J9,9=13.2
2
3
5
Hz, the other of H-9), 4.20 (ddd, 1H, J6,6=15.5, J6,7=5.3, J6,5a=1.7 Hz, the other of H-6), 4.58 (d, 1H,
3J=5.0 Hz, OCH2CH=CH2), 5.01 (d, 1H, 3J8b,7=17.2 Hz, H-8b), 5.06 (d, 1H, 3J8a,7=10.9 Hz, H-8a), 5.34
(dd, 1H, 3J=10.6, 2J=1.7 Hz, OCH2CH=CH2), 5.46 (dd, 1H, 3J=17.5, 2J=1.7 Hz, OCH2CH=CH2), 5.67 (s,
13
1H, H-2), 6.10 (m, 1H, OCH2CH=CH2), 6.91–7.57 (m, 9H, arom. CH). C NMR (75 MHz): δ 42.8
(C-6), 55.1 (C-5), 56.7 (C-9), 69.1 (OCH2CH=CH2), 74.7 (C-2), 111.9–157.7 (arom. CH and Cq), 117.6 and
117.7 (C-8 and OCH2CH=CH2), 132.3 and 133.1 (C-7 and OCH2CH=CH2), 171.1 (C-4, C=O). EI-MS;

m/z (%): 348.5 (1) [M+], 291.3 (28), 288.0 (6), 215.2 (100), 201.1 (17), 117.5 (16), 92.1 (7), 90.9 (100),
64.8 (9), 40.8 (15). Anal. Calcd for C22H24N2O2: C 75.83 H 6.94 N 8.04. Found C 75.81 H 6.89 N 7.99.
3-Allyl-1-benzylimidazolidin-4-one (3h): Flash chromatography (1:1) – Yellow oil. IR (NaCl): ν-1 =
3081 (w), 3062 (w), 3027 (w), 2919 (m), 2848 (w), 2802 (w), 1706 (s), 1496 (w), 1456 (m), 1373 (m),
1342 (m), 1139 (m), 931 (w), 746 (m), 701 (m). 1H NMR (300 MHz): δ 3.04 (dd, 1H, 2J6,6=15.5, 3J6,7=7.6
Hz, one of H-6), 3.26 (dd, 1H, 2J5a,5b=14.5, 5J5a,6=2.0 Hz, H-5a), 3.58 (d, 1H, 2J9,9=13.2 Hz, one of H-9),
2
2
3.69 (d, 1H, J5b,5a=14.5 Hz, H-5b), 3.81 (d, 1H, J9,9=13.2 Hz, the other of H-9), 4.29 (ddd, 1H,
2J6,6=15.5, 3J6,7=4.6, 5J6,5a=1.7 Hz, the other of H-6), 4.96 (dd, 1H, 3J8b,7=17.2, 2J8b,8a=0.8 Hz, H-8b), 5.11
(s, 1H, H-2), 5.15 (dd, 1H, 3J8a,7=10.2, 2J8a,8b=0.7 Hz, H-8a), 5.62 (m, 1H, H-7), 7.17–8.28 (m, 9H, arom.
13
CH). C NMR (75 MHz): δ 43.8 (C-6), 56.3 (C-5), 59.3 (C-9), 69.4 (C-2), 118.4 (C-8), 127.7–137.4
(arom. CH and Cq), 132.1 (C-7), 171.0 (C-4, C=O). EI-MS; m/z (%): 217.4 (7) [M++1], 216.4 (11) [M+],
215.2 (15), 175.2 (7), 174.0 (8), 131.9 (8), 75.0 (30), 92.1 (14), 90.9 (100), 64.8 (14), 41.9 (56). Anal.
Calcd for C13H16N2O: C 72.19 H 7.46 N 12.95. Found C 72.15 H 7.39 N 12.92.
3-Allyl-1-benzyl-2-(2-propyl)imidazolidin-4-one (3i): Flash chromatography (1:3) – Yellow oil. IR
(NaCl): ν-1 = 3062 (w), 3027 (w), 2964 (m), 2925 (m), 2873 (w), 1691 (s), 1525 (w), 1452 (w), 1263 (w),
1078 (w), 742 (w), 700 (m). 1H NMR (300 MHz): δ 0.85 (d, 3H, 3J=6.9 Hz, one of CH(CH3)2), 0.96 (d,
3H, 3J=6.9 Hz, the other of CH(CH3)2), 1.92 (m, 1H, CH(CH3)2), 3.13 (dd, 1H, 2J5,5=16.5 Hz one of H-5),
3.41 (dd, 1H, 2J6,6=15.5, 3J6,7=8.0 Hz, one of H-6), 3.51 (d, 1H, 2J5,5=16,5 Hz, the other of H-5), 3.70 (d,
1H, 3J9,9=13.2 Hz, one of H-9), 3.92 (d, 1H, 2J9,9=13.2 Hz, the other of H-9), 4.22 (s, 1H, H-2), 4.44 (dd,
1H, 2J6,6=15.5, 3J6,7=4.6 Hz, the other of H-6), 5.24 (d, 1H, 3J8a,7=10.6 Hz, H-8a), 5.25 (d, 1H, 3J8b,7=15.2
Hz, H-8b), 5.75 (m, 1H, H-7), 7.27–7.49 (m, 5H, arom. CH). 13C NMR (75 MHz): δ 14.8 (one of
CH(CH3)2), 18.4 (the other of CH(CH3)2), 31.3 (CH(CH3)2), 42.9 (C-6), 56.9 (C-5), 62.9 (C-9), 83.8 (C-2),
118.6 (C-8), 127.6–138.6 (arom. CH and Cq), 132.5 (C-7), 171.7 (C-4, C=O). EI-MS; m/z (%): 259.2
(6) [M++1], 257.2 (4), 216.5 (11), 215.3 (100), 91.0 (95), 64.9 (13), 40.8 (18). Anal. Calcd for
C16H22N2O: C 74.38 H 8.58 N 10.84. Found C 74.41 H 8.52 N 10.80.
1,3-Dibenzyl-2-(4-chlorophenyl)imidazolidin-4-one (3f): Flash chromatography (1:2) – Slightly yellow
Ph
crystals, mp 81-82o C (petroleum ether/ethyl acetate). IR (KBr): ν-1 = 3080 (m), 3064
7
H5a
H2
R
(m), 3029 (m), 2850 (w), 1710 (s), 1431 (m), 1411 (m), 1371 (w), 1098 (w), 701 (m). 1H
N1
5
4
H5b
O
2
2
5
N3
NMR (300 MHz): δ 3.28 (dd, 1H, J5,5=14.5, J=1.9 Hz, one of H-5), 3.59 (d, 1H,
2J5,5=14.5 Hz, the other of H-5), 3.77 (d, 1H, 2J7,7=13.2 Hz, H-7), 4.03 (d, 1H, 2J7,7=13.2
6
Ph

Hz, the other of H-7), 4.25 (d, 1H, 2J6,6=15.5, one of H-6), 4.63 (d, 1H, 2J6,6=15.5 Hz, the other of H-6),
4.83 (s, 1H, H-2), 7.20–7.49 (m, 14H, arom. CH). 13C NMR (75 MHz): δ 45.3 (C-6), 56.7 (C-5), 58.6 (C-9),
81.4(C-2), 126.6–147.3 (arom. CH and Cq), 171.8 (C-4, C=O). Anal. Calcd for C23H21N2OCl: C 73.30 H
5.62 N 7.43. Found C 73.25 H 5.64 N 7.41.
1,3-Dibenzyl-2-[4-(N,N-dimethylamino)phenyl]imidazolidine-4-one (3g): Flash chromatography (1:2)
– Slightly yellow crystals, mp 93-94o C (petroleum ether/ethyl acetate). IR (KBr): ν-1 = 3079 (m), 3063
1
(m), 3028 (m), 2851 (w), 1708 (s), 1439 (m), 1404 (m), 1375 (w), 1105 (w), 708 (m). H NMR (300
MHz): δ 3.00 (s, 6H, N(CH3)2), 3.34 (dd, 1H, 2J5,5=14.6, 5J=2.1 Hz, one of H-5), 3.62 (d, 1H, 2J5,5=14.6
Hz, the other of H-5), 3.77 (d, 1H, 2J7,7=13.1 Hz, H-7), 4.03 (d, 1H, 2J7,7=13.1 Hz, the other of H-7), 4.32
(d, 1H, 2J6,6=15.5, one of H-6), 4.69 (d, 1H, 2J6,6=15.5 Hz, the other of H-6), 4.87 (s, 1H, H-2), 7.19–7.49
(m, 14H, arom. CH). 13C NMR (75 MHz): δ 41.2 (N(CH3)2), 45.3 (C-6), 56.9 (C-5), 58.1 (C-9), 80.7(C-2),
126.1–147.7 (arom. CH and Cq), 171.4 (C-4, C=O). Anal. Calcd for C25H27N3O: C 77.89 H 7.06 N 10.90.
Found C 77.85 H 7.09 N 10.86.
3-Cyclohexyl-1-methyl-2-(4-chlorophenyl)imidazolidine-4-one (3j): Flash chromatography (1:1) –
Yellow oil. IR (NaCl): ν-1 = 2963 (s), 2853 (w), 1701 (s), 1412 (w), 1261 (w), 1086 (w),
H3C6
1
H
H2
1017 (m), 801 (m). H NMR (300 MHz): δ 0.88-1.74 (m, 10H, CH2 from cyclohexyl),
N1
5
4
3
5
2
H
O
2.20 (s, 3H, H-6), 3.12 (dd, 1H, J5,5=14.2, J=1.7 Hz, one of H-5), 3.40 (m, 1H, CH
R
N3
from cyclohexyl), 3.63 (dd, 1H, 3J5,5=14.2, 5J=1.7 Hz, the other of H-5), 4.70 (s, 1H, C-2),
R
13
7.34–7.37 (m, 4H, arom. CH). C NMR (75 MHz): δ 25.4 (CH2), 26.0 (CH2), 30.4 (CH2), 38.7 (C-6),
53.3 (CH from cyclohexyl), 57.6 (C-5), 82.7 (C-2), 128.9–137.8 (arom. CH and Cq), 171.4 (C-4, C=O).
EI-MS; m/z (%): 293.5 (3) [M++1], 292.4 (5) [M+], 291.3 (6), 182.4 (7), 181.2 (100), 166.1 (42), 99.0
(52), 55.0 (13), 43.9 (24). Anal. Calcd for C16H21N2OCl: C 65.63 H 7.23 N 9.57. Found C 65.59 H 7.25 N
9.55.
1-Methyl-2-(4-chlorophenyl)-3-(2-propyl)imidazolidin-4-one (3k): Flash chromatography (1:2) –
White crystals, mp 25-26° C (not recrystallized). IR (KBr): ν-1 = 2964 (m), 2852 (w), 2790 (w), 1704 (s),
1411 (w), 1261 (m), 1089 (m), 1018 (m), 800 (m). 1H NMR (300 MHz): δ 0.95 and 1.18 (d, 6H, 3J=6.9
3
5
Hz, NCH(CH3)2), 2.22 (s, 3H, H-6), 3.10 (dd, 1H, J5,5=14.2, J=1.7 Hz, one of H-5), 3.67 (dd, 1H,
3J5,5=14.2, 5J=1.0 Hz, the other of H-5), 3.69 (m, 1H, NCH(CH3)2), 4.67 (s, 1H, C-2), 7.34–7.37 (m, 4H,
13
arom. CH). C NMR (75 MHz): δ 20.0 and 20.5 (NCH(CH3)2), 38.6 (C-6), 45.0 (NCH(CH3)2), 57.7
(C-5), 82.9 (C-2), 128.9–137.6 (arom. CH and Cq), 171.4 (C-4, C=O). EI-MS; m/z (%): 253.4 (6) [M++1],

252.6 (7) [M+], 251.4 (8), 141.2 (100), 91.0 (58), 64.9 (16), 40.8 (28). Anal. Calcd for C13H17N2OCl: C
61.78 H 6.78 N 11.08. Found C 61.80 H 6.75 N 11.10.
3-Cyclohexyl-1-methyl-2-(2-propyl)imidazolidin-4-one (3l): Flash chromatography (1:3) – Yellow oil .
IR (NaCl): ν-1 = 2968 (m), 2930 (m), 2871 (w), 1695 (s), 1535 (w), 1445 (w), 1261 (w), 1075 (w), 740
(w), 700 (m). 1H NMR (300 MHz): δ 0.88-1.85 (m, 17H, CH(CH3)2 and CH2 from cyclohexyl), 2.20 (s,
3H, H-6), 3.12 (dd, 1H, 3J5,5=14.3, 5J=1.8 Hz, one of H-5), 3.40 (m, 1H, CH from cyclohexyl), 3.49 (d,
1H, 2J5,5=14.3 Hz, the other of H-5), 4.25 (s, 1H, H-2). 13C NMR (75 MHz): δ 14.7 (one of CH(CH3)2),
18.3 (the other of CH(CH3)2), 25.4 (CH2), 26.0 (CH2), 30.4 (CH2), 31.4 (CH(CH3)2), 53.3 (CH from
cyclohexyl), 42.9 (C-6), 57.4 (C-5), 83.8 (C-2), 172.1 (C-4, C=O). Anal. Calcd for C10H20N2O: C 65.18 H
10.94 N 15.20. Found C 65.11 H 10.91 N 15.24.
1,2-Dimethyl-3-(2-propyl)imidazolidin-4-one (3m): Flash chromatography (1:2) – Yellow oil. IR
(NaCl): ν-1 = 2964 (m), 2852 (w), 2790 (w), 1705 (s, C=O), 1411 (w), 1261 (m), 1089 (m), 1018 (m), 800
1
3
3
(m). H NMR (300 MHz): δ 0.95 and 1.17 (d, 6H, J=6.9 Hz, NCH(CH3)2), 1.68 (d, 3H, J=7.2 Hz,
CH3), 2.25 (s, 3H, H-6), 3.14 (dd, 1H, 3J5,5=14.2, 5J=1.7 Hz, one of H-5), 3.69 (dd, 1H, 3J5,5=14.2, 5J=0.9
3
13
Hz, the other of H-5), 3.75 (m, 1H, NCH(CH3)2), 4.62 (d, 1H, J=7.1 Hz, C-2). C NMR (75 MHz): δ
20.1 and 20.5 (NCH(CH3)2), 28.1 (CH3), 38.7 (C-6), 45.8 (NCH(CH3)2), 57.1 (C-5), 82.1 (C-2). Anal.
Calcd for C8H16N2OCl: C 61.50 H 10.32 N 17.93. Found C 61.48 H 10.34 N 17.91.
3-Cyclohexyl-1,2-dimethylimidazolidin-4-one (3n): Flash chromatography (1:3) – Yellow oil. IR
(NaCl): ν-1 = 2964 (m), 2929 (m), 2870 (w), 1701 (s), 1534 (w), 1446 (w), 1271 (w), 1071 (w), 741 (w),
701 (m). 1H NMR (300 MHz): δ 0.88-1.85 (m, 10H, CH2 from cyclohexyl and CH3), 2.21 (s, 3H, H-6),
3
5
3.12 (dd, 1H, J5,5=14.2, J=1.7 Hz, one of H-5), 3.40 (m, 1H, CH from cyclohexyl), 3.49 (d, 1H,
3
2J5,5=14,2 Hz, the other of H-5), 4.27 (d, 1H, J=7.2 Hz, H-2). 13C NMR (75 MHz): δ 14.7 (one of
CH(CH3)2), 18.3 (the other of CH(CH3)2), 25.4 (CH2), 25.4 (CH3), 26.0 (CH2), 30.4 (CH2), 31.4
(CH(CH3)2), 38.4 (C-6), 53.5 (CH from cyclohexyl), 57.4 (C-5), 82.8 (C-2), 171.7 (C-4, C=O). Anal.
Calcd for C11H20N2O: C 67.31 H 10.27 N 14.27. Found C 67.34 H 10.25 N 14.30.
ACKNOWLEDGEMENTS
The research has been supported by a grant of Ministry of Education (OC D29.002).
Dedicated to Professor Milan Kratochvíl on the occasion of his 80th birthday anniversary.

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