Two-step α-ureidoalkylation of ureas with 4,5-dihydroxyimidazolidin- 2-ones

Article abstract of DOI:10.1007/s11172-007-0024-1

Two-step α-ureidoalkylation of ureas with various 4,5-dihydroxyimidazolidin-2-ones gave novel 1,3-dialkyl-4,5-bis(3-alkylureido)-, 1,3-dialkyl-4,5-bis[3-(2-pyrimidyl)ureido]-, or 1,3-dialkyl-4,5-bis(3,3- dialkylureido)imidazolidin-2-ones and ensembles of three imidazolidine rings. The structure of 4,5-bis(2-oxoimidazolidin-1-yl)imidazolidin-2-one was confirmed by X-ray diffraction data. Springer Science+Business Media, Inc. 2007.

Full text of DOI:10.1007/s11172-007-0024-1

Russian Chemical Bulletin, International Edition, Vol. 56, No. 1, pp. 148—153, January, 2007
148
Twoꢀstep αꢀureidoalkylation of ureas
with 4,5ꢀdihydroxyimidazolidinꢀ2ꢀones
A. N. Kravchenko,aꢀ G. A. Gazieva,a A. S. Sigachev,a E. Yu. Maksareva,a K. A. Lyssenko,b and N. N. Makhovaa
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (495) 135 5328. Eꢀmail: kani@ioc.ac.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (495) 135 5508. Eꢀmail: kostya@xrlab.ineos.ac.ru
Twoꢀstep αꢀureidoalkylation of ureas with various 4,5ꢀdihydroxyimidazolidinꢀ2ꢀones gave
novel 1,3ꢀdialkylꢀ4,5ꢀbis(3ꢀalkylureido)ꢀ, 1,3ꢀdialkylꢀ4,5ꢀbis[3ꢀ(2ꢀpyrimidyl)ureido]ꢀ, or
1,3ꢀdialkylꢀ4,5ꢀbis(3,3ꢀdialkylureido)imidazolidinꢀ2ꢀones and ensembles of three imidazolidine
rings. The structure of 4,5ꢀbis(2ꢀoxoimidazolidinꢀ1ꢀyl)imidazolidinꢀ2ꢀone was confirmed by
Xꢀray diffraction data.
Key words: twoꢀstep αꢀureidoalkylation, 4,5ꢀdihydroxyimidazolidinꢀ2ꢀones; 1,3ꢀdialkylꢀ
4,5ꢀbis(3ꢀalkylureido)ꢀ, 1,3ꢀdialkylꢀ4,5ꢀbis[3ꢀ(2ꢀpyrimidyl)ureido]ꢀ, and 1,3ꢀdialkylꢀ4,5ꢀ
bis(3,3ꢀdialkylureido)imidazolidinꢀ2ꢀones; ensembles of three imidazolidine rings, Xꢀray difꢀ
fraction analysis.
It is known1 that ureidoalkylation reactions of ureas
DHI 2 with aminoguanidine hydrochloride leads to
4,5ꢀbis(3ꢀaminoguanidino)imidazolidinꢀ2ꢀone dihydroꢀ
chlorides (6) (see Ref. 9). Reactions of DHI with thiosemiꢀ
carbazide give both 4,5ꢀdi(thiosemicarbazido)imidazoꢀ
lidinꢀ2ꢀones (7) and 5,7ꢀdialkylꢀ3ꢀthioxoperhydroimidꢀ
azo[4,5ꢀe][1,2,4]triazinꢀ6ꢀones (8).8,9
with glyoxal afford 2,4,6,8ꢀtetraazabicyclo[3.3.0]octaneꢀ
3,7ꢀdiones (glycolurils) 1, 4,5ꢀdihydroxyimidazolidinꢀ2ꢀ
ones (DHI) 2, and imidazolidinꢀ2,4ꢀdiones (hydanꢀ
toins) 3.
In recent years, we have extensively studied αꢀureidoꢀ
alkylation of ureas,2 sulfamides,3—5 sulfonamides,4,5
ureido alcohols,6 ureido acids,6,7 thiosemicarbazide, and
aminoguanidine (in the hydrochloride form)8,9 with cyꢀ
clic vicinal ureidobis(αꢀcarbinols) 2 containing two poꢀ
tential αꢀureidoalkylating sites. We have developed genꢀ
eral methods for the targeted synthesis of various Nꢀsubꢀ
stituted glycolurils 1, including those containing hydrꢀ
oxy(carboxy)alkyl substituents, and their sulfur analogs.
Enantiomerically pure glycolurils have been first obtained
by diastereoselective or diastereospecific αꢀureidoalkylaꢀ
tion of optically pure Nꢀcarbamoylꢀαꢀamino acids.10,11
We have found that αꢀureidoalkylation of sulfamide, sulꢀ
fonamides, and aminoguanidine hydrochloride gives,
via unusual formation of the C=N bond, 4(5)ꢀsulfonylꢀ
iminoꢀ (4) and guanidinoiminoimidazolidinꢀ2ꢀones (5)
(see Refs 4, 5, 9). The second pathway of the reaction of
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 140—145, January, 2007.
1066ꢀ5285/07/5601ꢀ0148 © 2007 Springer Science+Business Media, Inc.

Twoꢀstep αꢀureidoalkylation of ureas
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 1, January, 2007
149
Here we systematically investigated twoꢀstep αꢀureidoꢀ
alkylation of various ureas (1ꢀalkylꢀ, 1ꢀarylꢀ, 1ꢀ(2ꢀpyriꢀ
midyl)ꢀ, and 1,1ꢀdialkylureas and imidazolidinꢀ2ꢀone
(ethyleneurea)12) with DHI.
bis[3ꢀ(2ꢀpyrimidyl)ureido]imidazolidinꢀ2ꢀones 9. The
yields of these compounds were 3—17% (9a—d,f,g,i,j),
70% (9e), and 92% (9h). In the case of cyclohexylurea
(10d), 2ꢀpyrimidylurea (10f), and phenylurea (10h), comꢀ
pounds 9e,g,h,j were the sole reaction products. Reacꢀ
tions of 1,3ꢀdiethylꢀDHI 2c with ureas 10c,g yielded only
glycolurils 1f,e, respectively. These facts suggest that the
structures of both DHI and ureas affect the pathway of the
ureidoalkylation of ureas 10. At the same time, ureas 10f,h
did not react with DHI 2c, being recovered unchanged.
Hydantoins 3a—c were obtained as byꢀproducts produced
by the pinacolꢀtype rearrangement9 of DHI (Scheme 1).
An increase in the reaction time to 1.5 h did not affect
the yields of the reaction products, only leading to inꢀ
creased amounts of the corresponding hydantoins 3.
Based on the aforesaid results, one can assume that
the predominant formation of 4,5ꢀbis(alkylureido)imidꢀ
azolidinꢀ2ꢀones 9 occurs with ureas containing a bulky
substituent at the N atom, which prevents possible cloꢀ
sure of a second ring. A similar result can be attained by
employing 1,1ꢀdialkylureas 11a,b in these reactions. To
verify the above assumption, we studied the αꢀureidoꢀ
alkylation of 1,1ꢀdimethylꢀ or 1,1ꢀdiethylureas (11a,b)
with DHI 2a,b and found that the reaction gives
4,5ꢀbis(3,3ꢀdialkylureido)ꢀ1,3ꢀdimethylimidazolidinꢀ2ꢀ
ones 12a—c in 13—52% yields and hydantoins 3a,b
(Scheme 2).
To obtain 4,5ꢀdisubstituted imidazolidinꢀ2ꢀones 9,
first we used 1ꢀalkylꢀ, 1ꢀphenylꢀ, and 1ꢀ(2ꢀpyrimidyl)ureas
10a—h in reactions with DHI 2a—c in the ratio 1 : 2
(DHI was added in portions) under the conditions of the
formation of 4,5ꢀdi(thiosemicarbazido)imidazolidinꢀ2ꢀ
ones (pH 1, 80 °C, 1 h). These reactions yielded products
of two types: earlier reported glycolurils 1a—g (comꢀ
pound 1h was characterized for the first time) and comꢀ
pounds producing doublets at δ 4.30—4.92 (CH—CH)
1
and 6.40—6.87 (NH) in H NMR spectra. The 1H NMR
spectra obtained match earlier unknown monocyclic comꢀ
pounds: 4,5ꢀbis(3ꢀalkylureido)ꢀ1,3ꢀdimethylꢀ, 1,3ꢀdiꢀ
methylꢀ4,5ꢀbis(3ꢀphenylureido)ꢀ, and 1,3ꢀdimethylꢀ4,5ꢀ
Scheme 1
Scheme 2
Reagents and conditions: i. pH 1, water or H2O—PriOH,
reflux, 1 h.
R = H (2a, 3a, 9g), Me (2b, 3b, 9a—f,h,j), Et (2c, 3c, 9i)
Proꢀ
duct
R
R´
Yield
(%)
Proꢀ
duct
R
R´
Yield
(%)
1a
1b
1c
1d
Me
Me
Me
Me
Pr
45
40
38
77
1e
1f
1g
1h
Et
Et
Me
Et
Bus
But
Et
35
65
48
Bu
Bus
But
cycloꢀC6H11
5
R1 = R2 = Me (11a), Et (11b)
Comꢀ
pound
R´
Product
Comꢀ
pound
R´
cycloꢀC6H11
Product
Compound
R
R1
R2
Yield (%)
12a
12b
12c
H
Me
Me
Me
Me
Et
Me
Me
Et
20
13
52
10a
10b
10c
10e
10g
10h
Et
Pr
But
Bun
Bus
Ph
9f
10d
9e,
9i
9g,
9h
9a
9d
9b
9c
9j
10f
Reagents and conditions: i. pH 1, water or H2O—PriOH,
reflux, 1 h.

150
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 1, January, 2007
Kravchenko et al.
O(1)
C(2)
The course of αꢀureidoalkylation of ethyleneurea 13
with DHI 2a—c was monitored by 1H NMR spectroꢀ
scopy. In the reaction of compound 2a with ethyleneurea,
a precipitate formed after 15 min; the amount of the preꢀ
cipitate increased with an increase in the reaction time.
No precipitation was observed in the reactions of DHI
2b,c with ethyleneurea 13. In the first case, the precipitate
was filtered off after 1 h and recrystallized from water. In
the other two cases, the reaction mixtures were concenꢀ
trated to oils that solidified upon treatment with methaꢀ
N(3A)
C(10A)
N(3)
C(4)
C(10)
C(9)
C(4A)
C(9A)
N(6)
N(6A)
C(7A)
1
nol—acetone (2 : 1). In the H NMR spectra, the major
O(2)
N(8)
C(7)
signals were broadened multiplets at δ 3.35—3.40 for the
CH2—CH2 groups of ethyleneurea, singlets at δ 5.10—5.20
for the CH—CH groups, and singlets at δ 6.50—6.75 for
two NH groups of ethyleneurea. The ratio of their intenꢀ
sities was 4 : 1 : 1. Therefore, both hydroxy groups in the
starting compounds 2a—c are replaced during the reacꢀ
tion by the ethyleneurea residue to give 4,5ꢀbis(2ꢀoxoimidꢀ
azolidinꢀ1ꢀyl)imidazolidinꢀ2ꢀones 14a—c, which are first
representatives of ensembles of three imidazolidine rings.
The yields of compounds 14a—c were 32—44%. Hydanꢀ
toins 3a—c were also isolated from the reaction mixtures
(Scheme 3).9
O(2A)
N(8A)
Fig. 1. General view of structure 14a.
oligomers. The optimized conditions were applied to reꢀ
actions of ethyleneurea with DHI 2b,c. The yields of comꢀ
pounds 14b and 14c were 53 and 40%, respectively.
To confirm the structures of products 14, we perꢀ
formed singleꢀcrystal Xꢀray diffraction analysis of comꢀ
pound 14a (Fig. 1). According to Xꢀray diffraction data,
this compound is an ensemble of three imidazolidine
rings. Compound 14a crystallizes as a racemate (space
group C2/c) with two hydration water molecules and is
characterized by the C2 symmetry with the transꢀarranged
terminal imidazolidine rings relative to the central one
(torsion angle N(6)—C(4)—C(4A)—N(6A) is –142.5°).
The central ring is in the twist conformation with the C(4)
and C(4A) atoms deviating by 0.19 Å, while the terminal
rings are in the envelope conformation with the C(9) atom
deviating by 0.11 Å (Table 1).
Scheme 3
An analysis of the crystal packing showed that molꢀ
ecules of 14a in the crystal are united through N—H...O
bonds (N...O 2.897(2) Å) into Hꢀbonded homochiral
layers (Fig. 2) running parallel to the crystallographic
plane bc. The Hꢀbonded rings form cavities each containꢀ
ing two water molecules (O...O 2.796(2)—2.826(2) Å). In
addition, water molecules link adjacent homochiral layꢀ
ers by N—H...O bonds (N...O 2.861(2) Å).
Table 1. Selected bond lengths (d) and angles (ω) in strucꢀ
ture 14a
R = H (a), Me (b), Et (c)
Reagents and conditions: i. pH 1—2, water, reflux, 1.5 h.
Bond
d/Å
Angle
ω/deg
The duration of the condensation of DHI 2a with
ethyleneurea 13 was optimized with the synthesis of comꢀ
pound 14a as an example. With an increase in the reacꢀ
tion time to 1.5 h, the yield of compound 14a increased
from 44 to 64%. After separation of compound 14a and
evaporation of the mother liquor to dryness, the 1H NMR
spectra contained no signals for the protons of the
nonconsumed starting reagents 13 and 2a, showing only
signals for the protons of hydantoin 3a and unidentified
O(1)—C(2)
O(2)—C(7)
C(2)—N(3)
C(4)—N(3)
C(4)—N(6)
N(6)—C(7)
N(6)—C(10)
N(8)—C(7)
N(8)—C(9)
1.230(3)
1.248(4)
1.349(3)
1.454(3)
1.435(3)
1.365(3)
1.459(3)
1.340(3)
1.439(4)
C(2)—N(3)—C(4)
111.6(2)
C(4)—N(6)—C(10) 123.7(2)
C(7)—N(6)—C(4) 123.8(2)
C(7)—N(6)—C(10) 111.9(2)
C(7)—N(8)—C(9) 113.0(2)

Twoꢀstep αꢀureidoalkylation of ureas
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 1, January, 2007
151
Fig. 2. Fragment of an Hꢀbonded homochiral layer in crystalline structure 14a.
Thus, we studied the twoꢀstep αꢀureidoalkylation of
various ureas (10, 11, and 13) with DHI 2 and demonꢀ
Experimental
NMR spectra were recorded on Bruker AMꢀ250 (1H,
250 MHz) and Bruker AMꢀ300 spectrometers (13C, 75.5 MHz).
Chemical shifts are given on the δ scale with reference to Me4Si
as the internal standard. Melting points were determined on a
GALLENKAMP instrument (Sanyo). Mass spectra were reꢀ
corded on a Kratos MSꢀ30 mass spectrometer (70 eV). 4,5ꢀDiꢀ
hydroxyimidazolidinꢀ2ꢀones were prepared by reactions of apꢀ
propriate ureas with glyoxal according to published proceꢀ
strated that these reactions give earlier unknown 4,5ꢀdiꢀ
substituted imidazolidinꢀ2ꢀones: 4,5ꢀbis(3ꢀalkylureido)ꢀ,
4,5ꢀbis(3ꢀphenylureido)ꢀ, 4,5ꢀbis[3ꢀ(2ꢀpyrimidyl)ureꢀ
ido]ꢀ, or 4,5ꢀbis(3,3ꢀdialkylureido)imidazolidinꢀ2ꢀones
and ensembles of three imidazolidine rings. Their strucꢀ
tures were confirmed by spectroscopic and Xꢀray diffracꢀ
tion data.
Table 2. Yields, melting points, and elemental analysis data for 4,5ꢀdisubstituted imidazolidinꢀ2ꢀones 1h, 9a—j, 12a—c, and 14a—c
Comꢀ Yield
M.p.
/°C
Found
Calculated
*
Molecular
formula
Comꢀ Yield
M.p.
/°C
Found
Calculated
*
(%)
Molecular
formula
(%)
poꢀ
(%)
poꢀ
(%)
und
und
C
H
N
C
H
N
1h
9a
9b
9c
9d
9e
9f
4—6
4—6
6—8
3—5
222—224 60.01 8.61 19.95 C14H24N4O2
59.98 8.63 19.98
198—200 49.69 8.31 26.71 C13H26N6O3
49.67 8.34 26.73
203—204 52.58 8.82 24.55 C15H30N6O3
52.61 8.83 24.54
208—210 52.63 8.81 24.53 C15H30N6O3
52.61 8.83 24.54
9i
9j
4—6
228—230 59.69 9.06 19.89 C21H38N6O3
59.64 9.08 19.91
8—10 283—285 61.45 6.38 20.47 C21H26N6O3
61.47 6.40 20.41
12a 18—21 176—178 41.85 7.02 32.54 C9H18N6O3
41.83 6.99 32.56
12b 12—14 220—221 46.14 7.74 29.35 C11H22N6O3
46.17 7.79 29.36
12c 51—53 198—199 52.61 8.83 24.54 C15H30N6O3
52.57 8.86 24.56
14a 62—64 250—252 42.52 5.55 33.05 C9H14N6O3
42.55 5.51 33.08
8—10 210—212 52.60 8.84 24.51 C15H30N6O3
52.61 8.83 24.54
90—92 230—232 57.87 8.70 21.27 C19H34N6O3
57.85 8.69 21.30
6—8
215—217 46.16 7.71 29.34 C11H22N6O3
46.14 7.74 29.35
14b 51—53 263—264 46.80 6.43 29.77 C11H18N6O3
46.79 6.45 29.74
9g
9h
15—17 206—208 43.60 3.93 39.06 C13H14N10O3
43.58 3.94 39.09
68—70 234—235 46.61 4.72 36.24 C15H18N10O3
46.63 4.70 36.25
14c 38—40 270—273 50.31 7.15 27.08 C13H22N6O3
50.34 7.17 27.05
* All the compounds obtained were pulverized and dried to remove the hydration water.

152
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 1, January, 2007
Kravchenko et al.
dures.5,13,14 Ureas were synthesized from KOCN and appropriꢀ
ate amine hydrochlorides according to known procedures.15
Aqueous 40% glyoxal, amines, KOCN, and ethyleneurea (Acros)
were used.
MeOH. Compounds 1a—c,e,g,h were extracted with CHCl3
(10×10 mL) and the extracts were concentrated in vacuo to an
oily residue, which were triturated with acetone—ether (1 : 3,
10 mL). The resulting precipitates of compounds 1a—c,e,g,h
were filtered off and crystallized from MeOH. The yields and
physicochemical characteristics of compounds 1a—g have been
reported earlier;2 those of product 1h is given in Table 2.
After the isolation of compounds 1a—h, the reaction mixꢀ
tures were concentrated to an oily residue, which was trituꢀ
rated in acetone (10 mL). The resulting precipitates of comꢀ
pounds 9a—d,f,i were filtered off and crystallized from MeOH.
Hydantoin 3a was isolated by trituration of the concentrated
filtrate with MeOH and filtration of the resulting precipiꢀ
tate; hydantoins 3b,c were isolated by extraction with Et2O folꢀ
lowed by concentration in vacuo. The physicochemical characꢀ
teristics of compounds 3a—c were in agreement with the literaꢀ
ture data.4
Synthesis of 6ꢀcyclohexylꢀ2,4ꢀdiethylꢀ2,4,6,8ꢀtetraazabiꢀ
cyclo[3.3.0]octaneꢀ3,7ꢀdione (1h); 1,3ꢀdimethylꢀ4,5ꢀbis(3ꢀproꢀ
pylureido)ꢀ (9a), 4,5ꢀbis(3ꢀbutylureido)ꢀ1,3ꢀdimethylꢀ (9b),
4,5ꢀbis(3ꢀsecꢀbutylureido)ꢀ1,3ꢀdimethylꢀ (9c), 4,5ꢀbis(3ꢀtertꢀ
butylureido)ꢀ1,3ꢀdimethylꢀ (9d), 4,5ꢀbis(3ꢀcyclohexylureido)ꢀ1,3ꢀ
dimethylꢀ (9e), 4,5ꢀbis(3ꢀethylureido)ꢀ1,3ꢀdimethylꢀ (9f), 1,3ꢀdiꢀ
methylꢀ4,5ꢀbis[3ꢀ(2ꢀpyrimidyl)ureido]ꢀ (9h), and 1,3ꢀdimethylꢀ
4,5ꢀbis(3ꢀphenylureido)imidazolidinꢀ2ꢀones (9j); 4,5ꢀbis[3ꢀ(2ꢀ
pyrimidyl)ureido]imidazolidinꢀ2ꢀone (9g); and 4,5ꢀbis(3ꢀcycloꢀ
hexylureido)ꢀ1,3ꢀdiethylimidazolidinꢀ2ꢀone (9i) (general proceꢀ
dure). Concentrated HCl (0.2 mL; in aqueous medium, to pH 1)
was added to a solution of appropriate urea 10a—h (0.02 mol)
and appropriate DHI 2a—c (0.01 mol) in a minimum amount of
water or propanꢀ2ꢀol (depending on the solubilities of the startꢀ
ing reagents). The reaction mixture was refluxed for 1 h. In the
case of urea 10c, the reaction mixture was concentrated by half
and left in a refrigerator for 12 h. The precipitate of compound
1d or 1f that formed was filtered off and recrystallized from
In the reactions of ureas 10d,f,h with DHI 2a,b, the reaction
mixtures were cooled to 20 °C and the resulting precipitates of
compounds 9e,g,h,j were filtered off and washed with MeOH.
The yields and physicochemical characteristics of comꢀ
pounds 9a—j are given in Tables 2—4.
Table 3. 1H NMR spectra (DMSOꢀd6) of compounds 1h, 9a—j, 12a—c, and 14a—c
Comꢀ
pound
δ, J/Hz
1h
9a
9b
9c
9d
9e
9f
1.16 (m, 10 Н, 2 Me, 2 СН2); 1.65 (m, 6 Н, 3 СН2); 3.03, 3.20 (both m, 2 H each, NСН2); 3.38 (m, 1 Н, NСН);
5.19, 5.31 (both d, 1 H each, 2 СН, J = 8.1); 7.56 (s, 1 Н, NH)
0.82 (t, 6 Н, 2 Me, J = 7.7); 1.36 (m, 4 Н, 2 СН2); 2.55 (s, 6 Н, 2 NMe); 2.95 (m, 4 Н, 2 NCH2);
4.91 (d, 2 Н, 2 СН, J = 8.3); 6.00 (t, 2 Н, 2 NH, J = 5.5); 6.62 (d, 2 Н, 2 NH, J = 8.3)
0.87 (t, 6 Н, 2 Me, J = 7.4); 1.32 (m, 8 Н, 4 СН2); 2.56 (s, 6 Н, 2 NMe); 3.01 (m, 4 Н, 2 NCH2);
4.91 (d, 2 Н, 2 СН, J = 8.8); 5.97 (t, 2 Н, 2 NH, J = 5.9); 6.62 (d, 2 Н, 2 NH, J = 8.8)
0.80 (m, 6 Н, 2 Me); 1.13 (m, 6 Н, 2 Me); 1.45 (m, 4 Н, 2 СН2); 2.57 (s, 6 Н, 2 NMe); 3.59 (m, 2 Н, 2 NСН);
4.87 (d, 2 Н, 2 СН, J = 8.6); 5.97 (m, 2 Н, 2 NH); 6.64 (d, 2 Н, 2 NH, J = 8.6)
1.21 (s, 18 H, 2 But); 2.48 (s, 6 H, 2 NMe); 4.30 (d, 2 Н, 2 СН, J = 8.5); 5.75 (s, 2 Н, 2 NH);
6.87 (d, 2 H, 2 NH, J = 8.5)
1.12 (m, 6 Н, 3 СН2); 1.30 (m, 4 Н, 2 СН2); 1.61 (m, 6 Н, 3 СН2); 1.79 (m, 4 Н, 2 СН2); 2.59 (s, 6 Н, 2 NMe);
3.39 (m, 2 Н, 2 NСН); 4.85 (d, 2 Н, 2 СН, J = 8.5); 5.73 (d, 2 Н, 2 NH, J = 7.9); 6.40 (d, 2 Н, 2 NH, J = 8.5)
0.99 (t, 6 Н, 2 Me, J = 7.2); 2.56 (s, 6 Н, 2 NMe); 3.03 (m, 4 Н, 2 NCH2); 4.92 (d, 2 Н, 2 СН, J = 8.3);
5.97 (t, 2 Н, 2 NH, J = 5.0); 6.66 (d, 2 Н, 2 NH, J = 8.3)
9g
9h*
9i
5.58 (d, 2 Н, 2 СН, J = 7.7); 6.63 (t, 2 Н, 2 СН, J = 4.8); 6.96 (br.s, 2 H, 2 NH); 7.88 (d, 2 Н, 2 NH, J = 7.7);
8.27 (d, 4 Н, 4 СН, J = 4.8)
2.63 (s, 6 Н, 2 Me); 5.59 (d, 2 Н, 2 СН, J = 8.6); 6.65 (t, 2 Н, 2 СН, J = 4.9); 7.84 (d, 2 Н, 2 NH, J = 8.6);
8.28 (d, 4 Н, 4 СН, J = 4.9)
1.09 (m, 12 Н, 2 Me + 3 СН2); 1.25 (m, 4 Н, 2 СН2); 1.55 (m, 6 Н, 3 СН2); 1.69 (m, 4 Н, 2 СН2);
3.03, 3.19 (both m, 2 H each, NСН2); 3.39 (m, 2 Н, 2 NСН); 4.89 (d, 2 Н, 2 СН, J = 8.5); 5.92 (d, 2 Н, 2 NH,
J = 6.6); 6.50 (d, 2 Н, 2 NH, J = 8.5)
9j
2.62 (s, 6 Н, 2 Me); 5.35 (d, 2 Н, 2 СН, J = 7.5); 6.63 (d, 2 Н, 2 NH, J = 7.5); 6.92 (t, 2 Н, 2 СН, J = 6.7);
7.22 (t, 4 Н, 4 СН, J = 6.7); 7.38 (d, 4 Н, 4 СН, J = 6.7); 8.69 (s, 2 Н, 2 NH)
2.79 (s, 12 Н, 2 NMe2); 5.20 (d, 2 Н, 2 СН, J = 7.7); 6.70 (br.s, 2 Н, 2 NH); 6.93 (d, 2 Н, 2 NH, J = 7.7)
2.57 (s, 6 H, 2 NMe); 2.80 (s, 12 H, 2 NMe2); 5.12 (d, 2 H, 2 CH, J = 7.3); 6.95 (d, 2 H, 2 NH, J = 7.3)
1.00 (t, 12 Н, 4 Me, J = 7.1); 2.84 (s, 6 H, 2 NMe); 3.05 (m, 8 Н, 4 СН2); 5.06 (d, 2 H, 2 CH, J = 7.6);
6.88 (d, 2 H, 2 NH, J = 7.6)
12a
12b
12c
14a
14b
14c
3.35 (m, 8 H, 4 CH2); 5.17 (s, 2 H, 2 CH); 6.50 (br.s, 2 H, 2 NH); 6.90 (s, 2 H, 2 NH)
2.61 (s, 6 H, NMe); 3.40 (m, 8 H, 4 CH2); 5.10 (s, 2 H, 2 CH); 6.75 (br.s, 2 H, 2 NH)
1.10 (m, 6 H, 2 Me); 2.75 (m, 2 H, NCH2); 3.11 (m, 2 H, NCH2); 3.37 (m, 8 H, 4 CH2); 5.20 (s, 2 H, 2 CH);
6.70 (s, 2 H, 2 NH)
*
13C NMR (DMSOꢀd6), δ: 27.9 (NMe); 68.7 (CH—CH); 111.6 (CH); 161.9 (CO).

Twoꢀstep αꢀureidoalkylation of ureas
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 1, January, 2007
153
Table 4. Mass spectra of compounds 9e and 14a—c
I > 2σ(I )), wR2 = 0.1020, and GOOF = 0.917 (for all reflecꢀ
tions). All calculations were performed with the SHELXTL
PLUS 5.0 program package.
Comꢀ
pound
m/z (Irel (%))
This work was financially supported by the Russian
Academy of Sciences (Program OKhꢀ10).
9e
252 (39) [М – NH2C(O)NHC6H11]+, 154 (90),
153 (23), 142 (19), 127 (100), 113 (40), 99 (22),
70 (22), 61 (43)
References
14a
14b
168 (5) [М – C3H6N2O*]+, 86 (100), 69 (8), 56 (11)
196 (100) [М – C3H6N2O*]+, 141 (10), 128 (11),
112 (12), 97 (9), 86 (8), 70 (10)
224 (63) [М – C3H6N2O*]+, 196 (15), 168 (14),
140 (33), 127 (25), 113 (27), 97 (31), 86 (100),
83 (32), 70 (62), 69 (37), 60 (18)
1. H. Petersen, Synthesis, 1973, 5, 273.
2. A. N. Kravchenko, A. S. Sigachev, E. Yu. Maksareva, G. A.
Gazieva, N. S. Trunova, B. V. Lozhkin, T. S. Pivina, M. M.
Il´in, Yu. V. Nelyubina, V. A. Davankov, O. V. Lebedev, N.
N. Makhova, and V. A. Tartakovsky, Izv. Akad. Nauk, Ser.
Khim., 2005, 680 [Russ. Chem. Bull., Int. Ed., 2005, 54, 691].
3. G. A. Gazieva, A. N. Kravchenko, and O. V. Lebedev, Usp.
Khim., 2000, 69, 239 [Russ. Chem. Rev., 2000, 69, 221 (Engl.
Transl.)].
4. G. A. Orekhova, O. V. Lebedev, Yu. A. Strelenko, and A. N.
Kravchenko, Mendeleev Commun., 1996, 68.
5. G. A. Gazieva, A. N. Kravchenko, O. V. Lebedev, Yu. A.
Strelenko, and K. Yu. Chegaev, Izv. Akad. Nauk, Ser. Khim.,
1998, 1604 [Russ. Chem. Bull., 1998, 47, 1561 (Engl.
Transl.)].
14c
* C3H6N2O is ethyleneurea.
Synthesis of 4,5ꢀbis(3,3ꢀdimethylureido)ꢀ (12a), 4,5ꢀbis(3,3ꢀ
dimethylureido)ꢀ1,3ꢀdimethylꢀ (12b), and 4,5ꢀbis(3,3ꢀdiethylꢀ
ureido)ꢀ1,3ꢀdimethylimidazolidinꢀ2ꢀones (12c) (general proceꢀ
dure). Concentrated HCl was added dropwise down to pH 1 to a
solution of an appropriate urea 11a,b (0.04 mol) and DHI 2a,b
(0.02 mol) in water (50 mL). The reaction mixture was stirred at
60—70 °C for 1 h. The resulting precipitates of compounds
12a—c were filtered off and washed with MeOH. The yields and
physicochemical characteristics of compounds 12a—c are given
in Tables 2 and 3. Hydantoins 3a,b were isolated as described
above.
6. A. N. Kravchenko, E. Yu. Maksareva, P. A. Belyakov, A. S.
Sigachev, K. Yu. Chegaev, K. A. Lyssenko, O. V. Lebedev,
and N. N. Makhova, Izv. Akad. Nauk, Ser. Khim., 2003, 180
[Russ. Chem. Bull., Int. Ed., 2003, 52, 192].
Synthesis of 1,3ꢀunsubstituted (14a), 1,3ꢀdimethylꢀ (14b),
and 1,3ꢀdiethylꢀ4,5ꢀbis(2ꢀoxoimidazolidinꢀ1ꢀyl)imidazolidinꢀ2ꢀ
ones (14c) (ensemble of three imidazolidine rings) (general proceꢀ
dure). A catalytic amount of HCl (pH 1) was added to an aqueꢀ
ous solution of ethyleneurea (imidazolidinꢀ2ꢀone) 13 (0.02 mol)
and an appropriate DHI 2a—c (0.01 mol). The reaction mixture
was refluxed for 1.5 h. In the case of product 14a, the precipitate
that formed was filtered off and recrystallized from water. In the
case of products 14b,c, the reaction mixture was thickened to an
oil and triturated with methanol—acetone (1 : 1). The resulting
precipitates of compounds 14b,c were filtered off and crystalꢀ
lized from MeOH. The yields and physicochemical characterisꢀ
tics of compounds 14a—c are given in Tables 2—4. Hydantoins
3a—c were isolated as described above.
Xꢀray diffraction analysis of compound 14a. The crystals of
compound 14a (C9H18N6O5) are monoclinic, space group C2/c,
at T = 120 K a = 11.759(2) Å, b = 9.335(2) Å, c = 11.386(3) Å, β
= 92.977(6)°, V = 1248.2(5) Å3, Z = 4 (Z´ = 0.5), M = 290.29,
dcalc = 1.545 g cm–3, µ(MoꢀKα) = 1.27 cm–1, F(000) = 616. The
intensities of 2478 reflections were measured on a Smart
1000 CCD automatic diffractometer at 120 K (2θ < 54°) and
1285 independent reflections (Rint = 0.04711) were used in calꢀ
culations. The structure was solved by the direct method and
refined by the fullꢀmatrix leastꢀsquares method in the anisotroꢀ
picꢀisotropic approximation on F 2. Hydrogen atoms were loꢀ
cated from the electron density difference maps. Final residuals
were R1 = 0.0504 (on F for 684 observed reflections with
7. A. N. Kravchenko and I. E. Chikunov, Usp. Khim., 2006, 75,
217 [Russ. Chem. Rev., 2006, 75, 191 (Engl. Transl.)].
8. A. S. Sigachev, A. N. Kravchenko, K. A. Lyssenko, P. A.
Belyakov, O. V. Lebedev, and N. N. Makhova, Mendeleev
Commun., 2003, 190.
9. A. S. Sigachev, A. N. Kravchenko, K. A. Lyssenko, P. A.
Belyakov, O. V. Lebedev, and N. N. Makhova, Izv. Akad.
Nauk, Ser. Khim., 2006, 836 [Russ. Chem. Bull., Int. Ed.,
2006, 55, 865].
10. A. N. Kravchenko, K. Yu. Chegaev, I. E. Chikunov, P. A.
Belyakov, E. Yu. Maksareva, K. A. Lyssenko, O. V. Lebedev,
and N. N. Makhova, Mendeleev Commun., 2003, 269.
11. I. E. Chikunov, A. N. Kravchenko, P. A. Belyakov, K. A.
Lyssenko, V. V. Baranov, O. V. Lebedev, and N. N.
Makhova, Mendeleev Commun., 2004, 253.
12. A. S. Sigachev, A. N. Kravchenko, E. Yu. Maksareva, B. V.
Lozhkin, K. A. Lyssenko, and N. N. Makhova, Mendeleev
Commun., 2006, 80.
13. H. Petersen, Liebigs Ann. Chem., 1969, 726, 89.
14. S. Vail, R. Barker, and P. Mennitt, J. Org. Chem., 1965, 30,
2179.
15. F. Arndt, Organic Syntheses, J. Wiley and Sons, Inc., New
York, 1935, 15, 48.
Received September 19, 2006;
in revised form November 17, 2006