4,5-dihydroxyimidazolidin-2-ones in an α-ureidoalkylation reaction of N-(carboxyalkyl)-, N-(hydroxyalkyl)-, and N-(aminoalkyl)ureas 3. * α-Ureidoalkylation of N-[2-(dimethylamino)ethyl]urea

Article abstract of DOI:10.1007/s11172-009-0348-0

α-Ureidoalkylation of N-[2-(dimethylamino)ethyl]urea with 1,3-unsubstituted, 1,3-dialkyl-, and 1,3-dimethyl-4,5-diphenyl-4,5- dihydroxyimidazolidin-2-ones(thiones) was systematically studied. Hitherto unknown N-[2-(dimethylamino)ethyl]glycolurils and their hydrochlorides were synthesized. The yields of the target glycoluril hydrochlorides decreased on going from 1,3-H₂- to 1,3-dialkyl-4,5-dihydroxyimidazolidin-2-ones and increased with the introduction of phenyl groups at the positions 4 and 5 of the starting 4,5-dihydroxyimidazolidin-2-one. X-ray diffraction study showed that 2-[2-(dimethylamino)ethyl]glycoluril crystallizes in the form of a conglomerate.

Full text of DOI:10.1007/s11172-009-0348-0

Russian Chemical Bulletin, International Edition, Vol. 58, No. 12, pp. 2488—2493, December, 2009
2488
4,5ꢀDihydroxyimidazolidinꢀ2ꢀones in an αꢀureidoalkylation reaction
of Nꢀ(carboxyalkyl)ꢀ, Nꢀ(hydroxyalkyl)ꢀ, and Nꢀ(aminoalkyl)ureas
3.* αꢀUreidoalkylation of Nꢀ[2ꢀ(dimethylamino)ethyl]urea
G. A. Gazieva,a P. V. Lozhkin,a V. V. Baranov,a Yu. V. Nelyubina,b A. N. Kravchenko,a and N. N. Makhovaa
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: gaz@server.ioc.ac.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. Eꢀmail: unelya@xrlab.ineos.ac.ru
αꢀUreidoalkylation of Nꢀ[2ꢀ(dimethylamino)ethyl]urea with 1,3ꢀunsubstituted, 1,3ꢀdialkylꢀ,
and 1,3ꢀdimethylꢀ4,5ꢀdiphenylꢀ4,5ꢀdihydroxyimidazolidinꢀ2ꢀones(thiones) was systematically
studied. Hitherto unknown Nꢀ[2ꢀ(dimethylamino)ethyl]glycolurils and their hydrochlorides
were synthesized. The yields of the target glycoluril hydrochlorides decreased on going from
1,3ꢀH2ꢀ to 1,3ꢀdialkylꢀ4,5ꢀdihydroxyimidazolidinꢀ2ꢀones and increased with the introduction
of phenyl groups at the positions 4 and 5 of the starting 4,5ꢀdihydroxyimidazolidinꢀ2ꢀone.
Xꢀray diffraction study showed that 2ꢀ[2ꢀ(dimethylamino)ethyl]glycoluril crystallizes in the
form of a conglomerate.
Key words: αꢀureidoalkylation, Nꢀcarbamoylation, coupling, Nꢀ[2ꢀ(dimethylamino)ethyl]ꢀ
glycolurils, Nꢀ[2ꢀ(dimethylamino)ethyl]urea, 4,5ꢀdihydroxyimidazolidinꢀ2ꢀones, conglomerate,
Xꢀray diffraction study.
Glycolurils (tetrahydroimidazo[4,5ꢀd]imidazoleꢀ
tals) is one of the simplest ways for an access to enantioꢀ
pure compounds. As has been shown in previous reports,1,6
one of the approaches to glycolurils that are able to crysꢀ
tallize as conglomerates can be the introduction of funcꢀ
tional groups that could be involved in hydrogen bond
formation in the substituents at the nitrogen atoms.
Carboxy, hydroxy, and amino groups are the examples
of such groups. We developed this approach in detail
by the example of synthesis of Nꢀ(carboxyalkyl)ꢀ and
Nꢀ(hydroxyalkyl)glycolurils among which three conꢀ
glomerates have been revealed.1,6,7
The aim of the present work was the development of a
method for the synthesis of Nꢀ[2ꢀ(dimethylamino)ethyl]ꢀ
glycolurils by ureidoalkylation of Nꢀ[2ꢀ(dimethylamino)ꢀ
ethyl]urea with 4,5ꢀdihydroxyimidazolidinꢀ2ꢀones or
4,5ꢀdihydroxyimidazolidineꢀ2ꢀthiones (DHI) and the
studies of an ability of the obtained Nꢀ(aminoalkyl)ꢀ
glycolurils to form conglomerates.
2,5(1H,3H)ꢀdiones) are novel class of neurotropic
drugs.2—5 Recently, novel daytime tranquilizer mebicar2
(2,4,6,8ꢀtetramethylglycoluril) has been introduced to the
medical practice in Russia, some other derivatives are on
different stages of adoption.
Over last several years, we have developed methods
for the synthesis of Nꢀ(carboxyalkyl)ꢀ and Nꢀ(hydroxyꢀ
alkyl)glycolurils starting from 4,5ꢀdihydroxyimidazolidinꢀ
2ꢀones and ureido acids or ureido alcohols.1,6 It was
demonstrated that the introduction of the carboxypropyl
fragment to one of the nitrogen atoms of glycoluril leads
to the manifestation of anxiolytic, sedative, and nootropic
effects comparable with the analogous action of mebicar.4,5
Analysis of structures of the known drugs that contain the
dialkylaminoalkyl fragment linked with the heterocyclic
nitrogen atom (aminazine, propazine, dinezine, and
others)2, allows one to expect that compounds with
novel types of the neurotropic activity will appear among
Nꢀ[2ꢀ(dimethylamino)ethyl]glycolurils.
Cyclocondensation of Nꢀ[2ꢀ(dimethylamino)ethyl]ꢀ
urea hydrochloride 1 with DHI 2a—e (Scheme 1) was
carried out in water or methanol depending on the reacꢀ
tant solubility with addition of different amount of HCl
at 60—80 °С for 0.5—2 h.
The search for methods of resolution of chiral glycolꢀ
urils to individual enantiomers is necessary for future
development of enantiopure drugs. The formation of
conglomerates (mixture of enantiomerically pure crysꢀ
The use of HCl for catalysis of cyclocondensation
leads to the formation of a mixture of products: hydroꢀ
* For Part 2, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2408—2412, December, 2009.
1066ꢀ5285/09/5812ꢀ2488 © 2009 Springer Science+Business Media, Inc.

αꢀUreidoalkylation of dimethylaminoethylurea
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 12, December, 2009 2489
Scheme 1
Table 1. Dependence of yields of Nꢀ[2ꢀ(dimethylamino)ꢀ
ethyl]glycolurils 3a,d on duration of reaction (τ) and amount of
HCl per 5 mmol of the starting DHI
DHI τ/h
HCl/mmol
Glycoluril
Yield (%)
2a
2a
2a
2a
2a
2a
2d
2d
2d
2d
2d
2d
2d
1
1
1
1
0.5
2
1
1
1
—
1
2.5
5
2.5
2.5
—
1
2.5
5
3a
3a
3a
3a
3a
3a
Traces
46
52
42
23
35
5
63
71
64
3d•MeOH
3d•MeOH
3d•MeOH
3d•MeOH
3d•MeOH
3d•MeOH
3d•MeOH
0.5
1
2
5
5
6
83
62
82
1
5 mmol decreased the yield of compound 3a to 42% beꢀ
cause of the increase in the yield of hydantoin 4a. Hydroꢀ
chloride 3d•MeOH is formed in maximum yield (83%)
upon addition of 5 mmol of HCl; the yield almost does
not change when the amount of HCl is increased to
6 mmol. The yields of hydrochlorides of glycolurils 3a and
3d•MeOH increases from 23 to 52 and from 64 to 83%,
respectively, with the increase in the reaction time from
0.5 to 1 h; subsequent increase in the reaction time to 2 h
leads to a decrease in the yield of 3a to 35% and in the
yield of 3d•MeOH to 62%. Analysis of the reaction prodꢀ
ucts showed that not all DHI 2a (or 2d) underwent the
reaction after 0.5 h, and a part of it was isolated unꢀ
changed from the reaction mixture. Part of DHI 2a transꢀ
2—4: X = O, R´ = H; R = H (a), Me (b), Et (c), R´ = Ph; R = Me (d),
X = S, R´ = Ph; R = Me (e)
chlorides of Nꢀ[2ꢀ(dimethylamino)ethyl]glycolurils 3a—e,
among which compounds 3d and 3e crystallized in the
form of solvates with methanol molecule, and hydantoins
4a—e, which are formed, as is known,8 in acid medium
from 4,5ꢀDHI by a pinacolꢀlike rearrangement.
The dependence of the final product yields on the
amount of HCl and the reaction duration was investiꢀ
gated. As is seen from Table 1, the maximum yield of
hydrochloride 3a (52%) is observed when 2.5 mmol
of HCl are used, the increase in the amount of HCl to
Table 2. Yields, melting points, and elemental analysis data for compounds 3a—e and 5a—c
Comꢀ
pound
Yield
(%)
M.p./
°С
Found
Calculated
Molecular
formula
(%)
N
C
H
Cl
3a
3b
3c
51—53
40—42
25—27
255—257
261—263
225—227
299—301
287—289
229—231
267—269
281—283
38.51
38.48
43.22
43.24
47.16
47.13
59.76
59.80
57.77
57.79
45.01
45.06
67.19
67.15
64.49
64.52
6.45
6.46
7.28
7.26
7.88
7.91
7.04
6.98
6.80
6.75
7.08
7.09
6.88
6.92
6.66
6.64
28.09 14.17
28.05 14.20
C8H16ClN5O2
C10H20ClN5O2
C12H24ClN5O2
C23H32ClN5O3
C23H32ClN5O2S
C8H15N5O2
25.18
12.78
25.21 12.76
22.92 11.56
22.90 11.59
3d•MeOH 81—83
3e•MeOH 63—65
15.15
15.16
14.62
14.65
32.88
32.84
17.76
17.80
17.08
17.10
7.76
7.67
7.47
7.42
—
5a
5b
5c
87—89
92—94
84—86
—
—
C22H27N5O2
C22H27N5OS

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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 12, December, 2009
Gazieva et al.
Table 3. 1H and 13C NMR spectra for compounds 3a—e and 5a—c (in DMSOꢀd6)
Comꢀ
pound
1Н, δ, J/Hz
13С {[H6]DMSO}, δ
3a
3b
3c
2.76 (s, 6 Н, NМе2); 3.12—3.18 (m, 1 H, NCH2);
3.24—3.38 (m, 2 H, NCH2); 3.52—3.62 (m, 1 H, NCH2);
5.23 (d, 1 H, CH, J = 8.1); 5.40 (d, 1 H, CH, J = 8.1);
7.37, 7.45 and 7.58 (all s, 1 H, NH); 10.23 (br.s, 1 H, N+H)
2.65 (s, 3 Н, NМе); 2.78 (s, 6 Н, NМе2); 2.86 (s, 3 Н, NМе);
3.16—3.41 (m, 3 H, NCH2); 3.69—3.81 (m, 1 H, NCH2);
5.16 (d, 1 H, CH, J = 9.5); 5.34 (d, 1 H, CH, J = 9.5);
7.91 (s, 1 H, NH); 10.54 (br.s, 1 H, N+H)
35.63 (NMe2); 42.32 (NСН2); 53.34 (NСН2);
62.39 (СH); 67.53 (СH); 159.25 (СО);
160.86 (СО)
27.83 (NМе); 30.78 (NMe); 36.57 (NMe2);
42.46 (NСН2); 53.37 (NСН2); 65.81 (СH);
70.92 (СH); 158.43 (СО); 159.45 (СО)
1.01—1.07 (m, 6 Н, Me); 2.76 (s, 6 Н, NМе2);
—
3.01—3.43 (m, 7 H, NCH2); 3.70—3.82 (m, 1 H, NCH2),
5.28 (d, 1 H, CH, J = 8.2); 5.46 (d, 1 H, CH, J = 8.2);
7.90 (s, 1 H, NH); 10.79 (br.s, 1 H, N+H)
3d•MeOH 2.60 (s, 3 Н, NМе); 2.77 (s, 6 Н, NМе2); 2.87 (s, 3 Н, NМе);
3.15—3.40 (m, 6 H, NCH2 + Me (MeOH)); 3.70—3.82 (m,
1 H, NCH2); 6.80—6.90 (m, 4 H, Ph); 7.06—7.14 (m, 6 H,
Ph); 8.85 (s, 1 H, NH); 10.91 (br.s, 1 H, N+H)
26.59 (NМе); 28.72 (NMe); 37.81 (NMe2);
42.62 (NСН2); 48.87 (Me (MeOH));
55.26 (NСН2); 83.14 (С—Ph); 88.09 (С—Ph);
127.61, 128.24, 128.73, 128.99, 132.93
and 134.77 (all Ph); 158.79 (СО); 159.96 (СО)
30.82 (NМе); 32.91 (NMe); 37.24 (NMe2);
42.54 (NСН2); 48.56 (Me (MeOH)); 54.76 (NСН2);
86.85 (С—Ph); 90.67 (С—Ph); 127.06, 128.15,
128.56, 128.83, 129.01, 131.93 and 133.44 (all Ph);
158.85 (СО); 182.99 (СS)
3e•MeOH 2.77 (s, 6 Н, NМе2); 2.91 (s, 3 Н, NМе); 3.00—3.08 (m,
1 H, NCH2); 3.16 (br.s, 6 Н, NМе + Me (MeOH));
3.22—3.40 (m, 2 H, NCH2); 3.83—3.91 (m, 1 H, NCH2);
6.78 (br.s, 4 H, Ph); 7.10—7.16 (m, 6 H, Ph);
9.12 (s, 1 H, NH); 10.91 (br.s, 1 H, N+H)
5a
5b
5c
2.42 (s, 6 Н, NМе2); 2.61—2.80 (m, 2 H, NCH2);
3.12—3.43 (m, 2 H, NCH2); 5.21 (d, 1 H, CH, J = 8.2);
5.32 (d, 1 H, CH, J = 8.2); 7.29 (s, 1 H, NH);
36.96 (NMe2); 43.76 (NСН2); 55.30 (NСН2);
62.24 (СH); 67.75 (СH); 159.13 (СО); 161.00 (СО)
7.40 (br.s, 2 H, NH)
2.10 (s, 6 Н, NМе2); 2.29—2.39 (m, 1 H, NCH2); 2.58—2.68 (m,
1 H, NCH2); 2.59 (s, 3 Н, NМе); 2.77—2.89 (m, 1 H, NCH2);
2.81 (s, 3 Н, NМе); 3.35—3.45 (m, 1 H, NCH2); 6.76—6.88 (m,
4 H, Ph); 7.06—7.12 (m, 6 H, Ph); 8.49 (s, 1 H, NH)
2.11 (s, 6 Н, NМе2); 2.15—2.27 (m, 1 H, NCH2); 2.51—2.61 (m,
1 H, NCH2); 2.87—2.89 (m, 1 H, NCH2); 2.92 (s, 3 Н,
NМе); 3.09 (s, 3 Н, NМе); 3.46—3.58 (m, 1 H, NCH2)
—
—
formed to hydantoin 4a. When the reaction was carried
out for 2 h, the amount of hydantoin 4a increased, and
DHI 2d was isolated along with hydrochloride of glycoluril
3d•MeOH. The formation of DHI 2d is probably due to
acid hydrolysis of hydrochloride 3d•MeOH. The formaꢀ
tion of hydantoin 4d was observed only after reflux for
several hours.
hydrochlorides 3a,d,e with sodium hydrogen carbonate
(Scheme 2). The upfield shift of the signals for the proꢀ
tons of the dimethylaminoethyl fragment by 0.2—0.7 ppm
was observed in the H NMR spectra of free bases 5a—c
in comparison with hydrochlorides 3a,d,e (Table 3).
1
Scheme 2
Considering the obtained results, syntheses of all
glycoluril hydrochlorides were carried out for 1 h, using
2.5 mmol of HCl for 3a—c, and 5 mmol of HCl for d,e.
The yields of hydrochlorides decreased on going from
3a (52%) to 3b (41%) and 3с (26%), and increased when
phenyl substituents were introduced in the positions
4 and 5 of the starting DHI (yield of glycoluril 3d•MeOH
was 83%, of its thio analog was 64%, see Table 2). Probꢀ
ably, phenyl substituents stabilize carbocations that are
formed upon dehydration of the starting DHI.6
Free bases 5a—c were obtained in good yields
(85—93%) by neutralization of aqueous solutions of
X = O, R = R´ = H (3a, 5a), R = Me, R´ = Ph (3d, 5b),
X = S, R = Me, R´ = Ph (3e, 5c)

αꢀUreidoalkylation of dimethylaminoethylurea
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 12, December, 2009 2491
Table 4. Selected bond lengths (Å) in 3a and 3d
Processes of crystallization of glycolurils 3a—e and
5a—c from water and methanol were investigated with
the aim to find conglomerates. Crystals of compounds 3a
and 3d that were obtained after crystallization from water
or methanol, respectively, were investigated by Xꢀray
method. Judging from Xꢀray investigation (Fig. 1, Table
4), spontaneous division (space group P21) was observed
for glycoluril 3a. Compound 3a represented conglomerꢀ
ate with S,Rꢀconfiguration of the chiral carbon atoms
Bond
d/Å
3a
3d*
C(1)—C(3)
C(1)—N(1)
N(1)—C(2)
C(2)—N(2)
N(2)—C(3)
C(3)—N(3)
N(3)—C(4)
C(4)—N(4)
N(4)—C(1)
N(2)—C(5)
N(2)—C(17)
1.552(5)
1.438(5)
1.365(5)
1.386(5)
1.449(5)
1.435(5)
1.357(5)
1.350(5)
1.453(5)
1.450(5)
—
1.588(3), 1.583(3)
1.435(3), 1.436(3)
1.364(3), 1.371(3)
1.378(3), 1.373(3)
1.469(3), 1.471(3)
1.449(3), 1.454(3)
1.380(3), 1.377(3)
1.366(3), 1.359(3)
1.464(3), 1.465(3)
—
C(1) and C(3). Salt 3d crystallized in centrosymmetrical
–
space group (P1). The main geometrical parameters for
imidazolidinꢀ2ꢀone fragments fell in the range which is
characteristic of this class of compounds.1,6
1.466(3), 1.462(3)
C(7)
* For two independent molecules.
C(8)
O(1)
N(5)
C(6)
According to analysis of supramolecular organization,
cations 3a «are packed» in crystal into homochiral layers
due to the hydrogen bond N(1)—H(1N)...O(2) (N...O
2.826(5) Å, NHO 154(1)°) and a shortened contact
O(1)...N(4) (N...O 3.065(5) Å, N(4)H(4N)O(1) 62(1)°).
Hydrogen bonds N(3)—H(3N)...Cl(1) (N...Cl 3.209(5)
Å, NHO 162(1)°), and N(5)—H(5N)...Cl(1) (N...O
3.075(5) Å, NHO 162(1)°) with the anion additionally
stabilize the cationic layer. The formation of such homoꢀ
chiral associate apparently leads to spontaneous resoꢀ
lution of the given salt in the crystallization.7,9,10 The
hydrogen bonds N(4)—H(4N)...Cl(1) (N...O 3.230(5) Å,
NHO 173(1)°) similar in strength and also some weaker
contacts (C—H…O, O...πꢀ and C—H...πꢀtype) complete
the formation of the threeꢀdimensional core.
Salt 3d, in contrast to 3a, represented crystall solvate
with methanol (3d : methanol ratio is 1 : 1) and two indeꢀ
pendent molecules of the target compound, and this led
to the ion packing different in principle. Although, simiꢀ
larly, hydrogen bonds were the main binding element,
direct interactions between the cations in the crystal
of 3d were absent. Symmetrically nonequivalent cations
linked with each other due to hydrogen bonds with
methanol, namely, the bonds N(1)—H(1N)...O(2S)
and N(6)—H(6N)...O(1S) where O...N 2.837(4) distꢀ
ance was 2.870(4) Å (NHO 165(1) is 168(1)°), bonds
O(2S)—H(2SO)...O(4) and O(1S)—H(1SO)...O(2) where
O...O distance was 2.758(4) — 2.770(4) Å (OHO 158(1)
is 170(1)°) forming heterochiral chains. The cation —
anion hydrogen bonds did not contribute to the stabilizaꢀ
tion of the chains; the chloride anions participated in the
formation of the hydrogen bonds only with the quaternary
nitrogen atom (N...Cl 3.059(3) is 3.073(3) Å, NHCl
174(1)°). These chains are assembled by weaker contacts,
for example, of the C—H...Oꢀ and C—H...πꢀtypes.
C(2)
C(5)
N(1)
N(2)
C(3)
N(4)
Cl(1)
N(3)
C(4)
O(2)
A
C(19)
C(1S)
C(20)
N(5)
O(1)
O(1S)
C(18)
C(17)
C(2)
N(2)
Cl(1)
C(22)
N(1)
N(4)
C(4) O(2)
C(21)
C(1)
C(3)
C(16)
N(3)
C(11)
C(5)
C(6)
C(7)
C(12)
C(15)
C(10)
C(13)
C(14)
C(8)
C(9)
B
Fig. 1. Overall view of salts 3a (a) and 3d (b, one independent
formula unit is displayed), atoms represented in the form of
thermal ellipsoids (p = 50%). Hydrogen atoms, except for
hydrogen atoms of the NH and OH groups, are not shown.
Thus, the αꢀureidoalkylation of Nꢀ[2ꢀ(dimethylꢀ
amino)ethyl]urea with 4,5ꢀdihydroxyimidazolidineꢀ

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Gazieva et al.
the residue was triturated with propanꢀ2ꢀol until solid precipitate
formed. In the case of 3d,e, the reaction mixture was cooled and
kept at room temperature for 24 h. The precipitate that formed
was filtered off.
2ꢀones was investigated, the methods for the synthesis
of hitherto unknown hydrochlorides and free bases of
Nꢀ[2ꢀ(dimethylamino)ethyl]glycolurils were developed.
A new conglomerate in the glycoluril series was found.
Synthesis of 2ꢀ[2ꢀ(dimethylamino)ethyl]glycouril (5a),
6ꢀ[2ꢀ(dimethylamino)ethyl]ꢀ2,4ꢀdimethylꢀ1,5ꢀdiphenylglycouril
(5b), and 1ꢀ[2ꢀ(dimethylamino)ethyl]ꢀ4,6ꢀdimethylꢀ5ꢀthioxoꢀ
3а,6аꢀdiphenylhexahydroimidazo[4,5ꢀd]imidazolꢀ2(1Н)ꢀone (5c)
(general procedure). NaHCO3 (0.06 g, 1 mmol) was added with
stirring to a solution of hydrochloride 3a (3d,e) (1 mmol) in
water (5 mL), the mixture was stirred at room temperature for
15 min, the precipitate of glycourils 5d,e that formed was filtered
off. In the case of 5a, the mixture was concentrated, the residue
was extracted with chloroform, then chloroform was evaporated.
XꢀRay diffraction studies of compounds 3a and 3d were carried
out on a Bruker SMART 1000 CCD difractometer (MoꢀKαꢀ
radiation, graphite monochromator, ωꢀscan). The structures
were solved by the direct method and refined by the leastꢀsquares
method in anisotropic fullꢀmatrix approximation for F2hkl. The
hydrogen atoms of the NH groups in structures 3a and 3d and of
the OH groups of solvate alcohol molecules in 3d are located
from the difference Fourier synthesis of the electronic density.
The positions of the remaining hydrogen atoms are calculated
geometrically. All hydrogen atoms are refined in isotropic
approximation using the «rider» model. The main crystalloꢀ
graphic data and parameters of refinement for 3a and 3d are
presented in Table 5. All calculation were carried out with a
program complex SHELXTL PLUS.11
Experimental
NMR spectra were recorded on Bruker AMꢀ250 (1H,
250.13 MHz (1Н)) and Bruker AMꢀ300 (300.13 (1H) and
75.5 MHz (13C) spectrometers in DMSOꢀd6, chemical shifts
are given in a δꢀscale relative to Me4Si as the internal standard.
Melting points were determined on a Gallenkamp (Sanyo)
apparatus.
Synthesis of hydrochlorides of 2ꢀ[2ꢀ(dimethylamino)ethyl]ꢀ
glycoluril (3a), 2,4ꢀdialkylꢀ6ꢀ[2ꢀ(dimethylamino)ethyl]glycolurils
(3b,c), 6ꢀ[2ꢀ(dimethylamino)ethyl]ꢀ2,4ꢀdimethylꢀ1,5ꢀdiphenylꢀ
glycoluril (3d), and 1ꢀ[2ꢀ(dimethylamino)ethyl]ꢀ4,6ꢀdimethylꢀ
5ꢀthioxoꢀ3а,6аꢀdiphenylhexahydroimidazo[4,5ꢀd]imidazolꢀ
2(1Н)ꢀone (3e) (general procedure). Mixtures of DHI 2a—e
(5 mmol) and urea 1 (0.67 g, 5 mmol) were dissolved in water
(5 mL) (2a—с) or methanol (15 mL) (2d,e) with stirring at
50 °C. Concentrated HCl was added (0.21 mL (2.5 mmol) in
the case of 3a—c and 0.42 mL (5 mmol) in the case of 3d,e)
and the mixture was stirred at 80 °C (aqueous solution) or
refluxed (methanol) for 1 h. In the case of 3a—с, the solvent was
evaporated, the obtained oily residue was extracted with ether,
Table 5. Main crystallographic data and refinement parameters
for salts 3a and 3d
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 08ꢀ03ꢀ
01070a) and Division of Chemistry and Materails Science
of the Russian Academy of Sciences (Program OСꢀ9 «Meꢀ
dicinal and Biomolecular Chemistry»).
Parameter
3a
3d
Molecular formula
Molecular weight
T/K
C8H16ClN5O2
249.71
120
C23H32ClN5O3
461.99
120
References
Crystal system
Space group
Z
Monoclinic
P21
Triclinic
P–1
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2
4
a/Å
b/Å
c/Å
α/deg
6.4178(5)
14.2997(10)
6.7498(5)
—
112.236(5)
—
573.38(8)
1.446
3.29
11.286(2)
11.3573(19)
18.252(3)
86.251(17)
81.112(16)
89.912(13)
2306.4(7)
1.330
β/deg
γ/deg
V/Å3
dcalc/g cm–3
μ/cm–1
2.01
F(000)
264
984
2θmax/deg
Number of reflections
measured
independent
with I > 2σ(I)
Number of refined
parameters
R1
57
54
6231
2997
2827
147
21952
10011
5571
587
0.0592
0.1643
0.0538
0.1248
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Belyakov, M. M. Il´in, V. V. Baranov, Yu. V. Nelyubina,
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Antipin, Izv. Akad. Nauk, Ser. Khim., 2009, 58, 390 [Russ.
Chem. Bull., Int. Ed., 2009, 58, 395].
wR2
GOOF
1.003
1.009
Residual electron
density/e•Å–3 (ρmax/ρmin
0.683/–0.421
0.582/–0.291
)

αꢀUreidoalkylation of dimethylaminoethylurea
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Recieved June 8, 2009