Oxidation of substituted imidazolidin-4-ones: New alternative method preparation of 4,5-dihydro-1H-imidazol-5-ones

Article abstract of DOI:10.1002/jhet.454

The reaction of aldehydes (pentanal, benzaldehyde, 4-methoxybenzaldehyde, 4-nitrobenzaldehyde, salicylaldehyde, pyridin-2-carbaldehyde) with 1-aminocyclopentancarboxamide or (S)-2-amino-2,3-dimethylbutanamide has been used to prepare substituted imidazolidin-4-ones 1a-g (a: R¹ = CH ₃(CH₂)₃; b: R¹ = C₆H ₅; c: R¹ = 4-CH₃OC₆H₄; d: R¹ = 4-NO₂C₆H₄; e: R¹ = 2-HOC₆H₄; f: R¹ = 2-pyridyl; for R² = R³ = (CH₂)₄), and g: R¹ = 2-pyridyl; for R² = CH₃; R³ = CH(CH ₃)₂) in the yields of 53-83%. Subsequent oxidations with various reagents gave the corresponding 4,5-dihydro-1H-imidazol-5-ones 2a-g: Pd/C (72-93%), DDQ (25-80%), and MnO₂ (30-77%). Structure of the prepared compounds 1a-g and 2a-g was verified by ¹H NMR and ¹³C NMR spectroscopy, EI-MS and elemental analysis. X-ray diffraction was performed in the case of compounds 1e and 2e.

Full text of DOI:10.1002/jhet.454

1356
Oxidation of Substituted Imidazolidin-4-ones: New Alternative
Method Preparation of 4,5-Dihydro-1H-imidazol-5-ones
Vol 47
a
Illia Panov, Pavel Drabina, Zdenka Padelkova, Jirı Hanusek,
a
b
a
ˇ
ˇ
´
ˇ´
a
and Milos Sedlak *
ˇ
´
aInstitute of Organic Chemistry and Technology, Faculty of Chemical Technology,
´
University of Pardubice, Studentska 573, Pardubice 532 10, Czech Republic
bDepartment of General and Inorganic Chemistry, Faculty of Chemical Technology,
´
University of Pardubice, Studentska 573, Pardubice 532 10, Czech Republic
*E-mail: Milos.Sedlak@upce.cz
Received December 23, 2009
DOI 10.1002/jhet.454
Published online 24 August 2010 in Wiley Online Library (wileyonlinelibrary.com).
The reaction of aldehydes (pentanal, benzaldehyde, 4-methoxybenzaldehyde, 4-nitrobenzaldehyde,
salicylaldehyde, pyridin-2-carbaldehyde) with 1-aminocyclopentancarboxamide or (S)-2-amino-2,3-dime-
thylbutanamide has been used to prepare substituted imidazolidin-4-ones 1a–g (a: R1 ¼ CH3(CH2)3; b:
R1 ¼ C6H5; c: R1 ¼ 4-CH3OC6H4; d: R1 ¼ 4-NO2C6H4; e: R1 ¼ 2-HOC6H4; f: R1 ¼ 2-pyridyl; for R2
¼ R3 ¼ (CH2)4), and g: R1 ¼ 2-pyridyl; for R2 ¼ CH3; R3 ¼ CH(CH3)2) in the yields of 53–83%. Sub-
sequent oxidations with various reagents gave the corresponding 4,5-dihydro-1H-imidazol-5-ones 2a–g:
Pd/C (72–93%), DDQ (25–80%), and MnO2 (30–77%). Structure of the prepared compounds 1a–g and
1
2a–g was verified by H NMR and 13C NMR spectroscopy, EI-MS and elemental analysis. X-ray dif-
fraction was performed in the case of compounds 1e and 2e.
J. Heterocyclic Chem., 47, 1356 (2010).
INTRODUCTION
A number of substituted 4,5-dihydro-1H-imidazol-5-
ones belong among still applied selective and non-toxic
herbicides [1]. Our previous articles dealt with their syn-
thesis, characterisation, and study of mechanism of their
formation [2]. Other possible applications of 4,5-dihy-
dro-1H-imidazol-5-ones lie in their use as ligands that
form coordination compounds with selected metal ions
[3]. Some of such complexes have been successfully
adopted as catalysts of deallylation reactions of diallyl
malonates [3b,f] in the Henry reaction [3c,e], or in allyl
oxidation [3i]. Another example of application of this
heterocyclic system is represented by 2-butyl-1,3-diazas-
piro[4.4]non-1-en-4-one, which is an important starting
compound for the synthesis of medical drug Irbesartan
(2-butyl-3-[[20-(1H-tetrazol-5-yl)-[1,10-biphenyl]-4-yl]methyl]-
1,3-diazaspiro[4.4]-nonen-4-on). Irbesartan is an antago-
nist of angiotensin II and is clinically applied in the
treatment of hypertension [4].
The existing methods of synthesis of 2-butyl-1,3-dia-
zaspiro[4.4]non-1-en-4-one use the acylation of amide
or nitrile of 1-aminocyclopentancarboxylic acid with
pentanoic acid chloride followed by ring closure reaction
[5]. Another method of preparation of 2-butyl-1,3-
C
V
2010 HeteroCorporation

November 2010
Oxidation of Substituted Imidazolidin-4-ones: New Alternative
Method Preparation of 4,5-Dihydro-1H-imidazol-5-ones
1357
Table 1
diazaspiro[4.4]non-1-en-4-one consists in acid catalyse
condensation of ethyl 1-aminocyclopentancarboxylate with
ethyl pentanimidate [6]. The third synthetic way described
is based on the reaction of 1-aminocyclopentanecarboxa-
mide with trimethyl orthopentanoate [7]. The described
variant of synthesis of 2-butyl-1,3-diazaspiro[4.4]non-1-
en-4-one is the reaction of pentanoic acid with 1-aminocy-
clopentannitrile [8]. The aim of the research described
here is to elaborate a new alternative synthetic method for
2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one and other sub-
stituted 4,5-dihydro-1H-imidazol-5-ones. This alternative
adopts oxidation of substituted imidazolidin-4-ones to give
4,5-dihydro-1H-imidazol-5-ones.
Oxidations 1 ! 2, yields obtained with individual reagents.
Catalyst/yield [%]
Entry
Product
Pd/C
DDQ
MnO2
1
2
3
4
5
6
7
2a
2b
2c
2d
2e
2f
80
87
83
93
72
90
72
25
40
73
80
77
75
38
65
75
77
30
67
70
64
2g
lowing oxidizing agents were used for this oxidation reac-
tion: palladium on carbon carrier (Pd/C), 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ), and activated manga-
nese (IV) oxide (MnO2). The results presented in the fol-
lowing table show that the first method (Pd/C) gives the
highest yields; however, in most cases the other two
(cheaper) variants are also applicable (Table 1).
RESULTS AND DISCUSSION
The reaction of aldehydes (pentanal, benzaldehyde, 4-
methoxybenzaldehyde, 4-nitrobenzaldehyde, salicylalde-
hyde, pyridin-2-carbaldehyde) with 1-aminocyclopentan-
carboxamide [5] or (S)-2-amino-2,3-dimethylbutanamide
[1] was used to prepare cyclic aminals, i.e., the corre-
sponding imidazolidin-4-ones 1a–g (a: R1 ¼ CH3(CH2)3;
b: R1 ¼ C6H5; c: R1 ¼ 4-CH3OC6H4; d: R1 ¼ 4-
NO2C6H4; e: R1 ¼ 2-HOC6H4; f: R1 ¼ 2-pyridyl; for R2
¼ R3 ¼ (CH2)4) and g: R1 ¼ 2-pyridyl; for R2 ¼ CH3;
R3 ¼ CH(CH3)2) (Scheme 1). The ring closure reaction
was performed with acid catalysis (acetic acid) by heating
the starting substances in methanol. Recrystallization gave
the respective imidazolidin-4-ones 1a–i in the yields of
53–83%. In the case of (5S)-4-isopropyl-4-methyl-2-(pyri-
din-2-yl)imidazolidine-4-one (1g), the reaction creates
another chiral centre at the carbon atom at 2-position of
the imidazolidin-4-one cycle. In this case, the reaction
produces a diastereomeric mixture with the configurations
2S, 5S and 2R, 5S, in the ratio of 1:1, which resulted in
doubling of signals in the NMR spectra.
Structures of the prepared products 1a–i and 2a–i
1
were verified by H NMR and 13C NMR spectroscopy,
EI-MS and elemental analysis. In the case of 2-(4-nitro-
phenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (2d), the
NMR spectra revealed the presence of two tautomeric
forms; a similar case was described and discussed in
Ref. 2b,c. The structure of product 2-(2-hydroxyphenyl)-
1,3-diazaspiro[4.4]nonan-4-one (1e) and its oxidation
product 2-(2-hydroxyphenyl)-1,3-diazaspiro[4.4]non-1-
en-4-one (2e) was also verified using X-ray diffraction.
In molecule 1e (Fig. 1), the bond distances in the central
heterocyclic ring clearly show that all of them are single
bonds. The only shortening of bond length is found in
the case of N3AC1 bond, which can be attributed to the
The second reaction step leading to the substituted 4,5-
dihydro-1H-imidazol-5-ones 2a-g was the oxidation of the
prepared imidazolidin-4-ones 1a–g (Scheme 1). The fol-
Scheme 1
Figure 1. Molecular structure of 1e, ORTEPꢀ 30% probability level.
˚
Selected interatomic distances [A] and angles [ ]: O(2)AC(1) 1.242(2),
C(1)AC(3) 1.516(3), C(3)AN(4) 1.483(3), N(4)AC(2) 1.465(3),
C(2)AN(3) 1.475(2), N(3)AC(1) 1.323(3), O(2)AC(1)AC(3) 124.91(19),
C(1)AC(3)AN(4) 102.51(15), C(3)AN(4)AC(2) 105.38(14), N(4)A
C(2)AN(3) 102.97(16), C(2)AN(3)AC(1) 111.82(17), N(3)AC(1)AC(3)
108.12(17), N(3)AC(1)AO(2) 126.94(18).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

ˇ ´ ´
I. Panov, P. Drabina, Z. Padelkova, J. Hanusek, and M. Sedlak
1358
Vol 47
Figure 2. Molecular structure of 2e, ORTEP 30% probability level.
ꢀ
˚
Selected interatomic distances [A] and angles [ ]:O(2)AC(2) 1.222(2),
C(2)AC(3) 1.522(3), C(3)AN(1) 1.476(3), N(1)AC(1) 1.285(3), C(1)A
N(2) 1.392(3), N(2)AC(2) 1.369(3), O(2)AC(2)AC(3) 128.50(19),
C(2)AC(3)AN(1) 103,75(16), C(3)AN(1)AC(1) 107.77(17), N(1)A
C(1)AN(2) 114.03(18), C(1)AN(2)AC(2) 108,72(17), N(2)AC(2)
AC(3) 105.73(17), N(2)AC(2)AO(2) 125.8(2).
Figure 4. Crystal packing diagram of 2e with hydrogen bonding
system.
and only dimers are formed by the connection of amido
group, and the imidazole nitrogen atom is connected to
the OAH group via the intramolecular H-bond which
fixed up the coplanarity of the aromatic ring (Fig. 4).
amido-character of the whole NHAC¼¼O group. Also
the C1AO2 interatomic distance corresponds to this
character. From the values of bond angles and interpla-
nar angles in this molecule is seen that the central ring
is fairly deformed by a distortion of N4 atom from the
ring core, and only five atoms (C1, C2, C3, N3, and
O2) tend to lie in a plane.
EXPERIMENTAL
If not stated otherwise, the starting substances were purchased
from Sigma-Aldrich. The melting point temperatures have not
been corrected. 1H NMR and 13C NMR spectra were recorded
on a Bruker Avance 500 instrument (500.13 MHz for 1H, and
125.77 MHz for 13C). Chemical shifts d are referenced to sol-
Both molecules 1e and 2e are mutually similar. The
main difference between them consists in the significant
shortening of N1AC1 distance in the case of 2e (Fig. 2),
which corresponds to a typical double bond [9]. This
fact the absence of the hydrogen atom at N1 atom and
high degree of planarity of the central heterocyclic ring
in this molecule are a proof of the oxidation of 1e–2e.
The molecules of compound 1e are interconnected to
the layered supramolecular structure via H-bonding
(Fig. 3). In the case of compound 2e, two independent
molecules were found in the crystal unit cell. The
H-bonding in compound 2e is slightly less extensive,
1
vent residual peak (2.50 ppm H, 39.43 ppm 13C for DMSO–d6,
1
and 7.26 ppm H, 77.00 ppm 13C for CDCl3). The mass spectra
were measured with a set of Agilent Technologies (gas chroma-
tograph 6890 N with mass detector 5973 Network); (the samples
were dissolved in dichloromethane or acetone). The elemental
microanalysis was carried out using an apparatus of FISONS
Instruments EA 1108 CHN. The optical rotation was measured
on a Perkin–Elmer 341 instrument; the concentration c was
given in g/100 mL (Optical rotatory power determination).
Crystallography. The X-ray data for colorless crystals of
1e and 2e were obtained at 150 K using an Oxford Cryostream
low-temperature device on a Nonius KappaCCD diffractometer
˚
with Mo Ka radiation (k ¼ 0.71073 A), a graphite monochro-
mator, and the / and v scan mode. Data reductions were per-
formed with DENZO-SMN [10]. The absorption was corrected
by integration methods [11]. Structures were solved by direct
methods (Sir92) [12] and refined by full matrix least-square
based on F2 (SHELXL97) [13]. Hydrogen atoms were mostly
localized on a difference Fourier map; however, to ensure uni-
formity of treatment of crystal, all the hydrogen atoms were
recalculated into idealized positions (riding model) and
assigned temperature factors Hiso (H) ¼ 1.2 Ueq(pivot atom) or
of 1.5 Ueq for the methyl moiety with CAH ¼ 0.96, 0.97,
˚
0.98, and 0.93 A for methyl, methylene, methane, and aro-
˚
˚
matic-ring hydrogen atoms, respectively; 0.86 A or 0.93 A for
˚
NAH, and 0.82 A for OAH bonds. The crystallographic data
for structural analysis have been deposited with the Cambridge
Crystallographic Data Centre, CCDC no. 757,260 and 757,259
Figure 3. Crystal packing diagram of 1e with hydrogen bonding
system.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Oxidation of Substituted Imidazolidin-4-ones: New Alternative
Method Preparation of 4,5-Dihydro-1H-imidazol-5-ones
1359
for 1e and 2e, respectively. [(Copies of this information may
be obtained free of charge from The Director, CCDC, 12
Union Road, Cambridge CB2 1EY, UK (fax: þ44-1223-
336033; e-mail: deposit@ccdc.cam.ac.uk or www: http://www.
ccdc.cam.ac.uk.)] In Figure 2, there is a disordered cyclopentane
ring. The disorder was treated by splitting of carbon atoms into
two positions with similar occupancy.
General method of preparation of imidazolidin-4-ones
(1a–g). A mixture of 1-aminocyclopentancarboxamide [5a]
(4.35 g; 34 mmol) or (S)-2-amino-2,3-dimethylbutanamide [1]
(4.40 g; 34 mmol) and the respective aldehyde (37 mmol), in
methanol (20 mL) with a drop of acetic acid was refluxed
12 h. The mixture was evaporated, and the residue was recrys-
tallized from the solvent given.
2-Butyl-1,3-diazaspiro[4.4]nonan-4-one (1a). Yield: 6.3 g
(96%); mp 72–74ꢀC (hexane). 1H NMR (CDCl3): d 0.85–0.87
(m; 3H, CH3), 1.25–1.32 (m; 4H, (CH2)2), 1.36–1.54 (m; 2H,
CH2), 1.55–1.64 (m; 6H, (CH2)3), 1.82–1.88 (m; 2H, CH2), 4.23
(t; 1H; J ¼ 6 Hz; CH), 8.13 (s; 1H; NH). 13C NMR (CDCl3,
ppm): d 13.7, 22.4, 25.1, 25.2, 26.7; 36.1; 36.5; 37.5; 68.5; 69.2;
182.0. Anal. Calcd. for C11H20N2O (196) (%): C, 67.31; H,
10.27; N, 14.27; found: C, 67.22; H, 10.38; N, 14.58.
(CDCl3) d 1.48–1.55 (m, 1H), 1.62–1.72 (m, 6H), 1.87–1.91 (m,
1H), 5.38 (s, 1H, CH), 7.34–7.37 (m, 1H, ArH), 7.49 (d, J ¼
7.69 Hz, 2H, Py), 7.82–7.85 (m, 1H, Py), 8.54–8.56 (m, 2H, Py
þ NH). 13C NMR (CDCl3) d 24.9, 36.7, 37.5, 68.4, 70.4, 121.7,
123.7, 137.3, 149.0, 159.9, 179.9; EI-MS: m/z 217, 188, 174
(100%), 145, 107, 79. Anal. Calcd. for C12H15N3O (217) (%):
C, 66.34; H, 6.96; N, 13.34. Found: C, 66.21; H, 6.85; N, 13.22.
(E + 2)(5S)-4-Isopropyl-4-methyl-2-(pyridin-2-yl)imidazolidin-
4-one (1g). Yield 1.51 g (74%); mp 113–118ꢀC (ethyl acetate/
1
hexane); [a]D ꢁ14.2 (c 1, CH3OH) H NMR (CDCl3) d 0.80–
0.99 (m, 12H, 2 ꢂ i.Pr), 1.20 (s, 3H, CH3), 1.26 (s, 3H, CH3),
1.83–1.91 (m, 2H, 2 ꢂ CH), 2.95 (br, 2H, NH), 5.48 (s, 1H, CH),
5.56 (s, 1H, CH), 7.15–7.18 (m, 2H, Py), 7.28 (d, J ¼ 7.6 Hz, 1H,
Py), 7.43 (d, J ¼ 7.6 Hz, 1H, Py), 7.62–7.65 (m, 2H, Py), 8.25 (s,
1H, NHCO), 8.37 (s, 1H, NHCO), 8.45–8.48 (m, 2H, Py). 13C
NMR (CDCl3) d 16.6, 16.7, 17.5, 17.6, 21.6, 23.2, 33.1, 34.5,
64.6, 64.7, 69.6, 71.1, 121.0, 123.3, 123.4, 136.8, 136.9, 148.9,
149.1, 158.7, 158.9, 180.5, 180.8. EI-MS: m/z 219, 204, 176
(100%), 133, 107, 92, 42. Anal. Calcd. for C12H17N3O (219) (%):
C, 65.73; H, 7.81; N, 19.16; found: C, 65.38; H, 7.56; N, 19.51.
General methods of preparation of 4,5-dihydro-1H-imi-
dazol-5-ones (2a–g)
2-Phenyl-1,3-diazaspiro[4.4]nonan-4-one (1b). Yield 2.49 g
(79%); mp 136–138ꢀC (ethyl acetate/hexane); 1H NMR
(CDCl3): d 1.49–1.76 (m, 7H), 1.81–1.90 (m, 1H), 3.13 (d, J
¼ 8.0 Hz, 1H, NH), 5.35 (d, J ¼ 8.0 Hz, 1H, CH), 7.30–7.44
(m, 5H, Ar), 8,55 (s, 1H, NHCO).13C NMR (CDCl3): d: 25.1,
25.2, 36.4, 37.2, 68.9, 69.7, 127.0, 128.4, 128.5, 142.1, 180.3.
EI-MS: m/z 216, 187, 173 (100%), 144, 106, 84. Anal. Calcd.
for C13H16N2O2 (216) (%): C, 72.19; H, 7.46; N, 12.95; found:
C, 72.01; H, 7.59; N, 13.12.
2-(4-Methoxyphenyl)-1,3-diazaspiro[4.4]nonan-4-one (1c). Yield
1.47 g (81%); mp 182–183ꢀC (ethyl acetate); 1H NMR
(CDCl3): d 1.47–1.70 (m, 7H), 1.82–1.87 (m, 1H), 3.71 (s, 3H,
OCH3), 5.27 (s, 1H, CH), 6.88–6.90 (m, 2H, Ar), 7.29–7.31
(m, 2H, Ar), 8.44 (s, 1H, NHCO). 13C NMR (CDCl3, ppm): d:
24.9, 36.1, 36.7, 55.2, 68.7, 69.1, 113.7, 128.1, 133.7, 159.4,
180.0; EI-MS: m/z 246, 217, 203 (100%), 134, 121, 84. Anal.
Calcd. for C14H18N2O2 (246) (%): C, 68.27; H, 7.37; N,
11.37; found: C, 68.45; H, 7.51; N, 11.50.
Method A (Pd/C). A mixture of the respective imidazoli-
din-4-one (5 mmol) and Pd/C (5%, 0.2 g) in methanol (50
mL) was refluxed 24 h. The final product was isolated after fil-
tration, evaporation, and (sometimes) recrystallisation from the
solvent given. In the case of isolation of compound 2d the
reaction mixture was evaporated, the residue was dissolved in
NaOH solution (5%, 25 mL), the solution was filtered and the
filtrate acidified to pH ꢃ 7–8. The separated crystals of com-
pound 2d were collected by filtration and dried. The final
product was recrystallized from DMF.
Method B (DDQ). A mixture of the respective imidazolidin-
4-one (5 mmol) and 2,3-dichloro-5,6-dicyano-1,4-benzoqui-
none (DDQ) (1.3 g, 5.7 mmol) in dioxane (50 mL) was
refluxed 10 min. The reaction mixture was filtered through a
silica gel layer (2 cm), evaporated and (sometimes) recrystal-
lized from the solvent given. In the case of isolation of com-
pound 2d the reaction mixture was evaporated, the residue was
dissolved in NaOH solution (5%, 25 mL), the solution was fil-
tered and the filtrate acidified to pH ꢃ 7–8. The separated
crystals of compound 2d were collected by filtration and dried.
The final product was recrystallized from DMF.
Method C (MnO2). A mixture of the respective imidazolidin-
4-one (5 mmol) and activated manganese (IV) oxide (5 g, 91
mmol) in acetone (100 mL) was refluxed 24 h. The final product
was isolated after filtration with kieselguhr, evaporation, and
(sometimes) recrystallization from the solvent given. In the case
of isolation of compound 2d, the reaction mixture was evapo-
rated, the residue was dissolved in NaOH solution (5%, 25 mL),
the solution was filtered and the filtrate acidified to pH ꢃ 7–8.
The separated crystals of compound 2d were collected by filtra-
tion and dried. The final product was recrystallized from DMF.
The yields of individual compounds are presented in Table 1.
2-Butyl-1,3-diazaspiro[4.4]non-1-en-4-one (2a). Colorless
oil, TLC: (silika gel plates, Merck), chloroform/methanol 10:1,
RF ¼ 0.51; 1H NMR (CDCl3) d 0.90 (t, 3H, CH3, J ¼ 7.3
Hz); 1.31–1.40 (m, 2H, CH2); 1.58–1.66 (m, 2H, CH2); 1.72–
1.80 (m, 3H); 1.83–1.93 (m, 5H, CH2); 2.42 (t, 2H, CH2, J ¼
7,4 Hz); 8.83 (bs, 1H, NHCO). 13C NMR (CDCl3) d 13.7;
23.1; 25.9; 27.9; 30.0; 37.2; 77.5; 190.2. Anal. Calcd. for
2-(4-Nitrophenyl)-1,3-diazaspiro[4.4]nonan-4-one (1d). Yield
0.92 g (53%); mp 178–180ꢀC (ethyl acetate); 1H NMR
(CDCl3): d 1.39–1.42 (m, 1H), 1.58–1.76 (m, 7H), 3.54 (d, J
¼ 7.5 Hz, 1H, NH), 5.46 (d, J ¼ 7.5 Hz, 1H, CH), 7.64–7.66
(m, 2H, Ar), 8.21–8.22 (m, 2H, Ar), 8.71 (s, 1H, NHCO). 13C
NMR (CDCl3): d 24.9, 25.0, 36.5, 37.6, 68.4, 68.5, 123.6,
128.2, 147.4, 150.0, 180.0; EI-MS: m/z 261, 232, 218 (100%),
151, 105, 84. Anal. Calcd. for C13H15N3O3 (261) (%): C,
59.76; H, 5.79; N, 16.08; found: C, 60.02; H, 5.95; N, 16.25.
2-(2-Hydroxyphenyl)-1,3-diazaspiro[4.4]nonan-4-one (1e). Yield
1
3.15 g (83%); mp 179–181ꢀC (ethyl acetate); H NMR(CDCl3)
d 4.48–1.56 (m, 1H), 1.59–1.80 (m, 6H), 1.85–1.90 (m, 1H),
5.60 (s, 1H, CH), 6.75–6.80 (m, 2H, Ar), 7.14 (t, J ¼ 7.5 Hz,
1H, Ar), 7.23 (d, J ¼ 7.5 Hz, 1H, Ar), 8.51 (s, 1H, NHCO),
10.96 (br, 1H, OH). 13C NMR (CDCl3) d 24.6, 24.8, 35.6,
36.8, 66.3, 67.9, 115.9, 118.6, 125.1, 127.7, 129.2, 156.4,
178.5. EI-MS: m/z 232, 188, 171 (100%), 113, 77, 44. Anal.
Calcd. for C13H16N2O2 (232) (%): C, 67.22; H, 6.94; N,
12.06; found: C, 67.35; H, 7.11; N, 12.31.
2-(2-Pyridyl)-1,3-diazaspiro[4.4]nonan-4-one (1f). Yield 1.62
g (80%); mp 109–111ꢀC (ethyl acetate/hexane); 1H NMR
Journal of Heterocyclic Chemistry
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I. Panov, P. Drabina, Z. Padelkova, J. Hanusek, and M. Sedlak
1360
Vol 47
REFERENCES AND NOTES
C11H18N2O (194) (%): C 68.01; H 9.34; N 14.42; Found: C
67.89; H 9.46; N 14.68.
[1] (a) Wepplo, P. J. Pestic Sci 1990, 31, 293; (b) Harris, J. E.;
Gagne, J. A.; Fischer, J. E.; Sharma, R. R.; Traul, K. A.; Scot, J. D.;
Hess, F. G. In The Imidazole Herbicides; Shaner, D. L.; O’Connor, S.
L., Eds.; CRC Press: Boca Raton, FL, 1991; p 179.
2-Phenyl-1,3-diazaspiro[4.4]non-1-en-4-one (2b). mp 202–
203ꢀC. 1H NMR (DMSO-d6) d 1.78–1.89 (m, 8H), 7.52–7.55
(m, 2H, Ar), 7.58–7.62 (m, 1H, Ar), 7.97–7.99 (m, 2H, Ar),
11.41 (br, 1H, NHCO). 13C NMR (DMSO-d6) d 25.6, 37.2,
77.6, 126.9, 128.7, 128.9, 131.5, 157.6, 188.1. EI-MS: m/z
214, 185, 171 (100%) 104, 83, 77, 54. Anal. Calcd. for
C13H14N2O (214) (%): C, 72.87; H, 6.59; N, 13.07. Found: C,
72.81; H, 6.52; N, 13.12.
´ ´
[2] (a) Sedlak, M.; Halama, A.; Kavalek, J.; Machacek, V.;
´ˇ
ˇ
Sterba, V. Collect Czech Chem Commun 1995, 60, 150; (b) Sedlak,
ˇ
´
ˇ
M.; Halama, A.; Kavalek, J.; Machacek, V.; Mitas, P.; Sterba, V. Col-
´
´ˇ
ˇ
ˇ
´
lect Czech Chem Commun 1996, 61, 910; (c) Sedlak, M.; Halama, A.;
ˇ
´ ´ˇ
Mitas, P.; Kavalek, J.; Machacek, V. J Heterocycl Chem 1997, 34,
2-(4-Methoxyphenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (2c). mp
236–237ꢀC. 1H NMR (CDCl3) d 1.92–2.09 (m, 8H), 3.87 (s,
3H, OCH3), 6.98–7.00 (m, 2H, Ar), 7.86–7.88 (m, 2H, Ar),
10.20 (br, 1H, NHCO). 13C NMR (CDCl3) d 25.6, 37.3, 55.6,
75.3, 114.3, 120.2, 129.6, 162.5, 162.7, 189.0. EI-MS: m/z
244, 215, 201, 134 (100%), 91, 83, 54. Anal. Calcd. for
C14H16N2O2 (244) (%): C, 68.83; H, 6.60; N, 11.47. Found: C,
68.78; H, 6.52; N, 11.55.
ˇ ´ ´
1227; (d) Mitas, P.; Sedlak, M.; Kavalek, J. Collect Czech Chem
´ ´ ˇ ´
Commun 1998, 63, 85; (e) Sedlak, M.; Kavalek, J.; Mitas, P.; Macha-
ˇ ´
cek, V. Collect Czech Chem Commun 1998, 63, 394; (f) Sedlak, M.;
´ ´ ´ˇ
Hanusek, J.; Bına, R.; Kavalek, J.; Machacek, V. Collect Czech Chem
´
Commun 1999, 64, 1629; (g) Sedlak, M.; Hanusek, J. Molecules 2000,
´
5, M177; (h) Sedlak, M.; Drabina, P.; Hanusek, J. Heterocycl Commun
2003, 9, 129.
´ ´ ˇ ´
˚ˇ ˇ
[3] (a) Sedlak, M.; Drabina, P.; Cısarova, I.; Ruzicka, A.;
´ˇ
Hanusek, J.; Machacek, V. Tetrahedron Lett 2004, 45, 7723; (b) Tur-
´
2-(4-Nitrophenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (2d). mp
>300ꢀC (dec.); 1H NMR (DMSO-d6) d 1.72–1.96 (m, 16H),
8.09–8.49 (m, 8H, 2 ꢂ 2Ar), 11.48 (s, 1H, NHCO), 11.58 (s,
1H, NHCO). 13C NMR (TFA þ DMSO-d6) d 28.9, 41.0, 77.4,
77.7, 124.0, 127.5, 130.0, 133.5, 133.9, 153.4, 156.5, 169.4,
169.7, 181.9, 182.1. Anal. Calcd. for C13H13N3O3 (259) (%):
C, 60.23; H, 5.05; N, 16.21. Found: C, 60.15; H, 4.98; N,
16.29.
ˇ ´
sky, M.; Necas, D.; Drabina, P.; Sedlak, M.; Kotora, M. Organometal-
´
lics 2006, 25, 901; (c) Sedlak, M.; Drabina, P.; Keder, R.; Hanusek, J.;
´
´ ˇ
˚ˇ ˇ
Cısarova, I.; Ruzicka, A. J Organomet Chem 2006, 691, 2623; (d) Dra-
´ ´
bina, P.; Hanusek, J.; Jirasko, R.; Sedlak, M. Transition Met Chem
´
2006, 31, 1052; (e) Keder, R.; Drabina, P.; Hanusek, J.; Sedlak, M.
ˇ ´
Chem Pap 2006, 60, 324; (f) Necas, D.; Drabina, P.; Sedlak, M.;
ˇ
Kotora, M. Tetrahedron Lett 2007, 45, 4539; (g) Mikysek, T.; Svan-
ˇ ˇ ´ ´
cara, I.; Bartos, M.; Vytras, K.; Drabina, P.; Sedlak, M.; Klıma, J.;
2-(2-Hydroxyphenyl)-1,3-diazaspiro[4.4]non-1-en-4-one (2e). mp
232–233ꢀC. 1H NMR (CDCl3) d 1.90–2.09 (m, 8H), 6.91 (t,
J ¼ 7.50 Hz, 1H, Ar), 7.01 (d, J ¼ 8.00 Hz, 1H, Ar), 7.35 (t,
J ¼ 8.00 Hz, 1H, Ar), 7.49 (d, J ¼ 7.50 Hz, 1H, Ar), 10.46
(vbs, 1H, NHCO), 12.46 (vbs, 1H, OH). 13C NMR (CDCl3)
d 25.4 37.4, 76.1, 110.7, 117.3, 118.9, 127.7, 133.5, 160.3,
161.3, 185.5. EI-MS: m/z 230, 189, 173 (100%), 120, 102, 84,
54. Anal. Calcd. for C13H14N2O2 (230) (%): C, 60.81; H, 6.13;
N, 12.17. Found: C, 60.78; H, 6.09; N, 12.24.
´ ´
Urban, J.; Ludvık, J. Electroanalysis 2007, 19, 2529; (h) Sedlak, M.;
´
´
Drabina, P.; Lansky, V.; Svoboda, J. J Heterocycl Chem 2008, 45,
˚ˇ ˇ
´ ˇ
859; (i) Drabina, P.; Sedlak, M.; Ruzicka, A.; Malkov, A.; Kocovsky,
´
P. Tetrahedron Asymmetry 2008, 19, 384.
[4] O’Neil, M. J. In The Merck Index—An Encyclopedia of
Chemicals, Drugs, and Biologicals, 13th ed.; O’Neil, M. J.; Smith, A.;
Hackelman, P. E., Eds.; Merck & Co.: Rahway, NJ, 2001; p 914.
[5] (a) Kavitha, C. V.; Gaonkar, S. L.; Narendra Sharath
Chandra, J. N.; Sadashiva, C. T.; Rangappa, K. S. Bioorg Med
`
Chem 2007, 15, 7391; (b) Cousaert, N.; Willand, N.; Gesquiere,
2-(1,3-Diazaspiro[4.4]non-1-en-4-one-2-yl)pyridine (2f). mp
120–122ꢀC. 1H NMR (DMSO-d6 þ TFA) d 1.96–2.12 (m,
8H), 7.45 (t, J ¼ 5.5 Hz, 1H, Py), 7.85 (t, J ¼ 7.5 Hz, 1H,
Py), 8.27 (d, J ¼ 7.50 Hz, 1H, Py), 8.67 (d, J ¼ 5.5 Hz, 1H,
Py), 10.12 (s, 1H, NHCO).13C NMR (DMSO-d6 þ TFA)
d 25.6, 37.1, 76.8, 122.7, 126.9, 137.6, 146.4, 149.4, 161.3,
187.4. EI-MS: m/z 215, 187 (100%), 159, 105, 78, 41. Anal.
Calcd. for C12H13N3O (215) (%): C, 66.96; H, 6.09; N, 19.52.
Found: C, 66.87; H, 6.02; N, 19.65.
(S)-2-(4-Isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-
2-yl)pyridine (2g). Colorless oil; [a]D ꢁ17.4 (c 2, CH3OH).
1H NMR (DMSO-d6 þ TFA) d 0.85 (d, 3H, J ¼ 6.8 Hz
i-PrCH3), 0.92 (d, 3H, J ¼ 6.8 Hz i-PrCH3), 1.23 (s, 3H,
CH3), 1.91 (m, 1H, i-PrCH), 7.57 (m, 1H, Py), 7.87 (m, 1H,
Py), 8.09 (d, 1H, J ¼ 7.4 Hz, Py), 8.18 (d, 1H, J ¼ 7.4 Hz,
Py), 10.87 (bs, 1H, NHCO).13C NMR (DMSO-d6 þ TFA)
d 16.8, 17.0, 21.4, 34.2, 74.6, 121.5, 126.5, 137.6, 147.4,
149.1, 159.0, 186.7. EI-MS: m/z 217, 202, 189, 174 (100%),
146, 105, 78. Anal. Calcd. for C12H15N3O (217) (%): C,
66.34; H, 6.96; N, 19.34. Found: C, 66.15; H, 6.85; N, 19.30.
J.-C.; Tartar, A.; Deprez, B.; Deprez-Poulain, R. Tetrahedron Lett
2008, 49, 2743.
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Wang, Q.-J. Zhongguo Yaowu Huxae Zazhi 2003, 13, 311;Chem Abstr
2005, 144, 88216.
[7] Huszar, C.; Kis-Tamas, A.; Nemeth, A.; Gajary, A.; Pali, L.
PCT Int Appl, WO 9905118, 1999; Chem Abstr 1999, 130, 168371.
[8] Huszar, C.; Kis-Tama, A.; Nemeth, A.; Gajary, A.; Kollar,
E.; Aranyosi, P.; Gyure, K.; Meszaros, I.; Csetrine, H. Z.; Supic, A.;
Dervalicsne, Z. I.; Dubovszki, K.; Pali, L.; Kunsztne, K. A.; Bognar,
E. PCT Int Appl, WO 9905120 A1 19990204, 1999; Chem Abstr
1999, 130, 139344.
[9] Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.;
Orpen, A. G.; Taylor, R. J Chem Soc Perkin Trans 1987, 2, S1.
[10] Otwinowski, Z.; Minor, W. Methods Enzymol 1997, 276,
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Hall, S. R.; Huber, C. P., Eds.; Munksgaard: Copenhagen, 1970;
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[12] Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi,
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[13] Sheldrick, G. M. SHELXL-97; University of Gottingen:
Acknowledgment. The authors acknowledge the financial sup-
port from the MSM 002 162 7501.
¨
Gottingen, 1997.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet