Synthesis and structure of 1,3-dialkyl-4-(sulfonylimino)imidazolidin-2-ones

Article abstract of DOI:10.1007/s10593-007-0153-3

The reactions of 1,3-dialkyl-4,5-dihydroxyimidazolidin-2-ones with alkyl sulfamides have been studied and previously undescribed 1,3-dialkyl-4- (alkylaminosulfonylimino)imidazolidin-2-ones have been obtained. The structure of 1,3-dimethyl-4-(benzenesulfonylimino)imidazolidin-2-one was investigated by X-ray structural analysis.

Full text of DOI:10.1007/s10593-007-0153-3

Chemistry of Heterocyclic Compounds, Vol. 43, No. 8, 2007
SYNTHESIS AND STRUCTURE OF 1,3-DIALKYL-
4-(SULFONYLIMINO)IMIDAZOLIDIN-2-ONES
G. A. Gazieva1, P. V. Lozhkin1, A. N. Kravchenko1, K. A. Lysenko2,
N. G. Kolotyrkina1, and N. N. Makhova1
The reactions of 1,3-dialkyl-4,5-dihydroxyimidazolidin-2-ones with alkyl sulfamides have been studied
and previously undescribed 1,3-dialkyl-4-(alkylaminosulfonylimino)imidazolidin-2-ones have been
obtained. The structure of 1,3-dimethyl-4-(benzenesulfonylimino)imidazolidin-2-one was investigated by
X-ray structural analysis.
Keywords: 1-alkylsulfamides, 1,3-dialkyl-4-(alkylaminosulfonylimino)imidazolidin-2-ones, 4,5-dihydroxy-
imidazolidin-2-ones, 1,3-dimethyl-4-(benzenesulfonylimino)imidazolidin-2-one, X-ray structural
analysis.
Imidazolidin-2-one derivatives possess a broad spectrum of biological activity. In particular, hydantoins
are used in medicine and agrochemistry as anticonvulsants [1, 2], anticancer preparations [3], fungicides [4], and
herbicides [5]. On the other hand compounds containing a sulfamide fragment display bacteriostatic,
hypoglycemic, diuretic, and herbicidal action [2, 6-8]. For several years the reactions of 4,5-dihydroxy-
imidazolidin-2-ones (DHI) with ureas and their hetero analogues have been among our scientific interests.
Recently as a result of investigations carried out by us on the interaction of 1-alkyl and 1,3-dialkyl-DHI with
sulfamide and amides of sulfonic acids, an unusual reaction has been detected [9] leading to
4,4'-sulfonyldiiminobis(1,3-dialkylimidazolidin-2-one) 1 and 4(5)-aryl(or alkyl)-sulfonyliminoimidazolidin-
2-one 2, containing both pharmacophoric fragments. We later showed that the reaction of 1,3-dialkyl-DHI with
aminoguanidine proceeds analogously with the formation of 1,3-dialkyl-4-guanidinoiminoimidazolidin-2-ones 3
[10].
R
R1
N
R1
N
R
N
N
NH
O
O
O
O
.
HCl
N
R
N
R2
N
R2
NSO2R3
N
R
NNHCNH2
NSO2N
1
2
3
With the aim of broadening the scope of the discovery, the reaction of 1,3-dialkyl-DHI 4a,b with
1-alkylsulfamides 5a-d under conditions analogous to the conditions of obtaining compounds 2 and 3 (methanol,
HCl) (Scheme 1) has been investigated.
__________________________________________________________________________________________
1N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991; e-mail:
2
gaz@server.ioc.ac.ru. A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of
Sciences, Moscow 119991; e-mail: kostya@xrlab.ineos.ac.ru. Translated from Khimiya Geterotsiklicheskikh
Soedinenii, No. 8, pp. 1159-1166, August, 2007. Original article submitted October 19, 2006.
0009-3122/07/4308-0981©2007 Springer Science+Business Media, Inc.
981

Scheme 1
R1
N
R1
N
R1
N
OH
OH
H2NSO2NHR2
+
O
O
O
+
N
NSO2NHR2
N
N
R1
O
5a-d
R1
R1
6a-h
7a,b
4a,b
4a, 6a, c, e, g, 7a R1 = Me; 4b, 6b, d, f, h, 7b R1 = Et; 5a, 6a, b R2 = Pr;
5b, 6c, d R2 = Bu; 5c, 6e, f R2 = s-Bu; 5d, 6g, h R2 = cyclo-C6H11
1
Analysis of the reaction products was carried out by H NMR spectroscopy of the reaction mass after
evaporation to dryness. In these spectra characteristic signals were detected for the protons of the N-alkyl groups
(0.83-3.49), the CH2 group of the imidazolidine ring (4.44-4.48), and the NH group of the sulfamide fragment
(7.00-7.12 ppm), from the intensities of which it may be suggested that the reaction products are the previously
unknown 1,3-dialkyl-4-(alkylaminosulfonylimino)imidazolidin-2-ones 6a-h. In the 3.9-4.0 ppm region signals
were also recorded for the CH2 group protons of hydantoins 7a,b, which are formed as byproducts. Hydantoins
7a,b were not isolated.
After isolation in a pure state the structures of compounds 6a-h were confirmed by a combination of
data of elemental analysis, IR, 1H NMR, and mass spectra (Tables 1, 2).
TABLE 1. Characteristics of Compounds 6a-h
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
mp, °C
Yield, %
С
H
N
S
6a
6b
6c
6d
6e
6f
C8H16N4O3S
C10H20N4O3S
C9H18N4O3S
C11H22N4O3S
C9H18N4O3S
C11H22N4O3S
C11H20N4O3S
C13H24N4O3S
38.72
38.70
43.45
43.46
41.22
41.21
45.52
45.50
41.18
41.21
45.53
45.50
45.78
45.82
49.38
49.35
6.52
6.49
7.31
7.29
6.88
6.92
7.67
7.64
6.91
6.92
7.64
7.64
7.03
6.99
7.67
7.65
22.55
22.56
20.31
20.27
21.39
21.36
19.26
19.29
21.38
21.36
19.27
19.29
19.51
19.43
17.69
17.71
12.88
12.91
11.55
11.60
12.17
12.22
10.99
11.04
12.19
12.22
11.01
11.04
11.07
11.12
10.10
10.13
64-66
71-73
37-39
50-52
43-45
51-53
29-31
36-39
33-35
41-44
72-74
65-67
89-91
86-88
6g
6h
117-119
120-124
In the IR spectra of compounds 6a-h a broad absorption peak is observed for the sulfamide NH bond at
3244-3292 cm-1, and also intense absorption for the C=O bond at 1728-1760 cm-1. Stretching vibrations for the
C=N bond are displayed at 1612-1624, and for the S=O bond at 1248-1344 cm-1 (Table 2).
Analysis of the mass spectra of sulfonylimines 6a,b,d,f-h showed the general character of the
fragmentation. Peaks were present for molecular ions in the spectra of all the investigated compounds. The
positive charge is localized predominantly on the sulfamide nitrogen atoms.
982

TABLE 2. Spectral Characteristics of Compounds 6a-h
IR spectrum,
Com-
pound
Mass spectrum,
m/z (I, %)
1Н NMR spectrum, δ, ppm (J, Hz)
ν, cm-1
6a
6b
3284, 1736,
1618, 1320,
1260
0.85 (3H, t, J = 7.3, CH3); 1.45 (2H, m, CH2); 248 (5), 219 (48),
2.70 (3H, s, NCH3), 2.74 (3H, s, NCH3);
2.84 (2H, m, NCH2), 4.48 (2H, s, CH2);
6.97 (1H, br. s, NH)
190 (100), 140 (35),
127 (36), 126 (32),
112 (29), 98 (10), 97 (13),
83 (41)
3292, 1728,
1612, 1340,
1316, 1248
0.86 (3H, t, J = 7.5, CH3);
1.09 (6H, t, J = 7.0, 2CH3);
1.47 (2H, m, CH2), 2.85 (2H, m, NCH2);
3.33, 3.49 (both 2H, m, NCH2);
4.48 (2H, s, CH2), 7.12 (1H, t, J = 6.5, NH)
276 (12), 247 (19),
218 (100), 154 (67),
153 (84), 140 (62),
127 (25), 112 (30),
109 (47), 97 (18), 83 (79)
6c
3266, 1754,
1622, 1344,
1316, 1252
0.83 (3H, t, J = 6.7, CH3);
1.27 (2H, m, CH2); 1.39 (2H, m, CH2);
2.84 (3H, s, NCH3); 2.90 (3H, s, NCH3);
4.44 (2H, s, CH2); 7.08 (1H, br. s, NH)
6d
3276, 1736,
1624, 1320,
1252
0.83 (3H, t, J = 7.3, CH3);
1.06 (6Н, t, J = 7.0, 2CH3);
1.27 (2H, m, CH2); 1.40 (2H, m, CH2);
2.87 (2H, m, NCH2); 3.30 (2H, m, NCH2);
3.47 (2H, m, NCH2); 4.45 (2H, s, CH2);
7.06 (1H, t, J = 5.8, NH)
290 (5), 247 (23),
218 (100), 155 (48),
154 (74), 140 (15),
127 (17), 112 (15),
99 (7), 83 (46)
6e
6f
3268, 1760,
1624, 1318,
1252
0.83 (3H, t, J = 7.3, CH3);
1.07 (3Н, d, J = 6.1, CH3);
1.40 (2H, m, CH2); 2.85 (3H, s, NCH3);
2.90 (3H, s, NCH3); 3.16 (1H, m, NCH);
4.45 (2H, s, CH2); 7.00 (1H, d, J = 8.0, NH)
3252, 1760,
1620, 1344,
1304, 1252
0.82 (3H, t, J = 7.3, CH3);
290 (2), 261 (64),
218 (100), 154 (18),
153 (52), 127 (13),
111 (16), 83 (44)
1.06 (9Н, m, 3CH3); 1.38 (2H, m, CH2);
3.17 (1H, m, NCH); 3.28 (2H, m, NCH2);
3.45 (2H, m, NCH2); 4.45 (2H, s, CH2);
7.01 (1H, d, J = 7.9, NH)
6g
6h
3264, 1760,
1624, 1312,
1296
1.09-1.91 (10H, m, 5CH2);
288 (30), 245 (49),
190 (100), 127 (35),
126 (39), 112 (16),
98 (53), 97 (21), 83 (45)
2.88 (3H, s, NCH3); 2.93 (3H, s, NCH3);
3.10 (1H, m, CH); 4.47 (2H, s, CH2);
7.04 (1H, d, J = 7.3, NH)
3244, 1760,
1624, 1344,
1316, 1296,
1252
1.04-1.86 (16H, m, 2CH3 + 5CH2);
3.05 (1H, m, CH); 3.31 (2H, m, NCH2);
3.46 (2H, m, NCH2); 4.46 (2H, s, CH2);
7.09 (1H, d, J = 7.9, NH)
316 (9), 273 (43),
235 (15), 218 (100),
154 (56), 153 (74),
140 (9), 127 (25),
112 (13), 111 (13),
98 (59), 83 (56)
A characteristic of the mass spectra of all compounds 6 was the primary alkylamine splitting of radical
R2 (ions F1, Scheme 2), and also elimination of fragments R2NH with the formation of ions F2, the peaks of
which were maximal in the mass spectra of all the investigated compounds. Primary routes of breakdown of the
molecular ions of compounds 6 were also characterized by splitting of the second N-S bond with elimination of
the sulfamide substituent, and the process was accompanied by the partial transfer of hydrogen to the imine
nitrogen atom (ions F3 and F4). One further unusual route of fragmentation of the molecular ions of
imidazolidinones 6 was linked with the splitting off entirely of all the sulfodiamide fragment (possibly from the
resonance form B) with the formation of the odd-electron ion F5. The initial fragment ions F2-F5 of compounds 6
with radicals R1 = C2H5 eliminate a molecule of ethylene by a 1,5-sigmatropic transfer of hydrogen (McLafferty
rearrangement).
983

984

During the investigation a dependence was discovered of the yields of compound 6 on the length of the
carbon chain of substituents at the nitrogen atom of the DHI. Unsubstituted DHI does not react with sulfamides
with the formation of a C=N bond, but on going from 1,3-dimethyl (6a,c,e,g) to 1,3-diethyl DHI (6b,d,f,h) the
yields of the corresponding products 6 increased (see Table 1).
The new direction for the reaction of N-alkyl-DHI with urea heteroanalogs therefore has a fairly general
character. Under acid catalysis conditions several types of imino derivatives of imidazolidin-2-one 1-3, 6 were
obtained. For unequivocal proof of structure of the obtained compounds an X-ray diffraction analysis was
carried out in the present work on the example of 4-(benzenesulfonylimino)-1,3-dimethylimidazolidin-2-one 2a,
synthesized by the procedure of [9].
Fig. 1. General form of compound 2a.
Fig.2. O…π and C-H…O bonded dimer in the 2a crystal.
985

In the crystal of 2a, according to X-ray crystallographic data, the imidazolidine ring is in fact planar with
the maximum deviation by atom C(2) of 0.088(7) Å [atoms N(1), N(3), C(4), and C(5) are coplanar with a
precision of 0.007 Å] (Fig. 1).
Analysis of the ring bond lengths in the 2a crystal showed that the N(3) atom is involved in conjugation
with the C(4)–N(6) double bond, while the unshared electron pair of the N(1) atom on the other hand, is coupled
with the C=O bond. In reality, the C(2)–N(1) bond is appreciably shorter [1.345(2) Å] than the C(2)–N(3) bond
[1.414(2) Å] and in fact is not distinguished from the N(3)–C(4) bond [1.360(2) Å] (Table 3). The observed
differences also lead to variation of the configuration of the ring nitrogen atoms. Atom N(3) is characterized by a
planar configuration, while atom N(1) deviates insignificantly from the plane of its substituents. The sum of the
valence angles for the N(1) and N(3) nitrogen atoms are equal to 355.7(1) and 359.6(1)° respectively.
Analysis of the intermolecular interactions in the 2a crystal showed that the O(2) atom of the sulfo group
forms fairly unusual interactions with the π-system of the imidazolidine ring, and there is also C–H…O contact
[O(2)…H(5BA) 2.43 Å] with the hydrogen atom on atom C(5). The indicated contacts unite the molecules in a
centrosymmetric dimer (Fig. 2).
The presence of fairly short intermolecular contacts O(2)…C [3.114(3)-3.153(3) Å and O(2)…N
[3.001(3)-3.252(3) Å], and also the size of the O(2)…ring centroid (2.854 Å) distance indicate with a high
probability the presence of a specific O…π interaction [11]. However (see for example [12]) it is impossible to
exclude that the indicated combination of intermolecular contacts is obligatory and the formation of the dimer is
caused solely by the C–H…O contact.
TABLE 3. Main Bond Lengths (d) in the Compound 2a Molecule
Bond
d, Å
Bond
d, Å
S(1)–O(2)
1.4363(15)
1.4404(15)
1.6408(14)
1.2195(19)
1.299(2)
C(4)–N(3)
1.3600(19)
1.506(2)
1.414(2)
1.345(2)
1.457(2)
S(1)–O(3)
S(1)–N(6)
O(1)–C(2)
C(4)–N(6)
C(4)–C(5)
N(3)–C(2)
N(1)–C(2)
N(1)–C(5)
TABLE 4. Main Valence Angles (ω) in the Compound 2a Molecule.
Angle
ω, deg
Angle
ω, deg
O(2)–S(1)–O(3)
O(2)–S(1)–N(6)
O(3)–S(1)–N(6)
O(2)–S(1)–C(7)
O(3)–S(1)–C(7)
N(6)–S(1)–C(7)
N(6)–C(4)–N(3)
N(6)–C(4)–C(5)
N(3)–C(4)–C(5)
C(4)–N(3)–C(2)
117.6(1)
106.72(9)
112.55(8)
108.03(8)
108.01(8)
102.83(7)
120.7(1)
132.5(1)
106.8(1)
111.5(1)
C(4)–N(3)–C(14)
C(2)–N(3)–C(14)
C(2)–N(1)–C(13)
C(2)–N(1)–C(5)
C(13)–N(1)–C(5)
O(1)–C(2)–N(1)
O(1)–C(2)–N(3)
N(1)–C(2)–N(3)
C(4)–N(6)–S(1)
125.4(1)
122.70(1)
122.43(1)
111.63(1)
121.72(1)
128.7(2)
124.2(1)
107.1(1)
120.4(1)
986

EXPERIMENTAL
The 1H NMR spectra were recorded on a Bruker AM 300 (300 MHz) spectrometer in DMSO-d6, internal
standard was TMS. Mass spectra were obtained on a MS 30 mass spectrometer, and IR spectra on a Specord M
82 spectrometer (in KBr disks).
X-Ray Structural Investigation of Compound 2a. Crystals of compound 2a, grown in methanol, were
triclinic at 110 K: a = 8.0462(10), b = 8.2895(10), c = 9.2004(11) Å, α = 88.276(2), β = 84.394(2),
γ = 85.481(2)°, V = 608.67(13) Å3, dcalc = 1.458 g.cm-3, space group P , Z = 2. The intensities of 6003
1
reflections were measured on a Smart 1000 CCD automatic diffractometer at 110 K (MoKα radiation, graphite
monochromator, ω-scanning, 2θmax = 58°) and 3358 (Rint = 0.0163) observed reflections were used in the
subsequent calculations. The structure was interpreted by the direct method and was refined by the full matrix
least squares method in an anisotropic-isotropic approach on F2. The hydrogen atoms were located in electron
density difference syntheses and were refined with a rider model. Final divergence factors: wR2 = 0.1057,
GOF = 1.037 according to the reflections (R1 = 0.0466 calculated on 2279 reflections with I >2σ(I)) with the
SHELXTL PLUS set of programs.
1,3-Dimethyl- [13], 1,3-diethyl-DHI [9], and 1-alkylsulfamides were synthesized by reported methods.
1,3-Dialkyl-4-(alkylaminosulfonylimino)imidazolidin-2-ones 6a-h (General Method). The
appropriate 1,3-dialkyl-4,5-dihydroxyimidazolidin-2-one 4a,b and 1-alkylsulfamide 5a-d (about 5 mmol of
each) were dissolved in methanol (5 ml). Conc. HCl (2 drops) was added and the mixture boiled for 30 min.
After cooling the reaction mass the precipitated solid compound 6e-h was filtered off and recrystallized from
methanol–water, 1:4. To obtain products 6a-d the solvent was distilled off on a rotary evaporator. Compounds
6a (Rf = 0.74), 6b (Rf = 0.77), 6c (Rf = 0.84), 6d (Rf = 0.80) were isolated by column chromatography on SiO2
(40 x 100), using an acetone–chloroform, 1:3 mixture.
The work was carried out with the support of the Russian Academy of Sciences OKh-10 program.
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