X-ray crystal structure of 2,5-dioxo-4-imidazolidineethanesulfonamide, C5H9N3O4S

Article abstract of DOI:10.1023/A:1023833211325

The crystal structure of 2,5-dioxo-4-imidazolidineethanesulfonamide or homocysteine sulfonamide hydantoin, C₅H₉N ₃O₄S (1) was obtained by single-crystal X-ray diffraction. Crystallization of 1 occurs in the centrosymmetric monoclinic space group C2/c (No. 15) with a = 15.653(2), b = 9.6489(10), c = 11.066(2) A, β = 94.64(2)°, and Z = 8. Molecules are in an extended structure with a C-C-C-S torsion angle of -174.2(1)°. The imidazolidinedione ring is planar and the sulfonamide group has a distorted tetrahedral geometry. A three-dimensional network of intermolecular hydrogen bonding occurs within the crystal lattice involving both imidazolidinedione and sulfonamide functional groups.

Full text of DOI:10.1023/A:1023833211325

C
Journal of Chemical Crystallography, Vol. 33, No. 4, April 2003 ( 2003)
X-ray crystal structure of
2,5-dioxo-4-imidazolidineethanesulfonamide, C5H9N3O4S
Jason A. Kautz,(1) Christine Chang,(1) Ce Qin,(1) and Mary Lynn Trawick(1)
Received July 27, 2002
The crystal structure of 2,5-dioxo-4-imidazolidineethanesulfonamide or homocysteine sul-
fonamidehydantoin, C5H9N3O4S(1)wasobtainedbysingle-crystalX-raydiffraction. Crys-
tallization of 1 occurs in the centrosymmetric monoclinic space group C2/c (No. 15) with
˚
a = 15.653(2), b = 9.6489(10), c = 11.066(2) A, = 94.64(2) , and Z = 8. Molecules
--- --- ---
C C S torsion angle of 174.2(1) . The imidazo-
are in an extended structure with a C
lidinedione ring is planar and the sulfonamide group has a distorted tetrahedral geometry.
A three-dimensional network of intermolecular hydrogen bonding occurs within the crystal
lattice involving both imidazolidinedione and sulfonamide functional groups.
KEY WORDS: Synthesis; crystal structure; hydrogen bonds; imidazolidine; sulfonamide; homocysteine;
hydantoin; imidazolidinedione.
of both glutamine synthetase1 and glutamate
synthase.2
Introduction
(R, S)-2,5-Dioxo-4-imidazolidineethanesul-
fonamide(2) or 5-(2-sulfamoylethyl)-2,4-imidazo-
lidinedione, the hydantoin of D,L-homocysteine
sulfonamide(3-amino-3-carboxypropanesulfona-
mide), is an analog of the amino acid glutamine
in which both the amino and carboxyl functional
groups are protected as the hydantoin (imidazo-
lidinedione) and the side-chain carboxamide is
replaced with the sulfonamide functional group
(Scheme 1). Sulfonamides are commonly found
in therapeutic agents and have been used to
replace carboxamides in some substrates to make
analogs that inhibit a number of enzyme-catalyzed
reactions. Such analogs retain the potential to
H-bond. 3-Amino-3-carboxypropanesulfonamide
(homocysteine sulfonamide) acts as an inhibitor
Scheme 1.
Experimental
Synthesis
The hydantoin of D,L-homocysteine sulfonam-
ide, 2,5-dioxo-4-imidazolidineethanesulfonamide,
(1) Department of Chemistry and Biochemistry, Baylor University,
Waco, Texas 76798-7348.
To whom correspondence should be addressed. E-mail:
mary lynn trawick@baylor.edu
(2)Separate numbering schemes are used for organic nomenclature
and for the crystal structure.
277
C
1074-1542/03/0400-0277/0 2003 Plenum Publishing Corporation

278
Kautz, Chang, Qin, and Trawick
ethyl) disulfide,5,6 then oxidatively chlorinated
to give D,L-5-( -chlorosulfonylethyl)hydantoin.
Liquid ammonia (150 mL) was condensed in a
round bottom flask that contained 4.5 g (20 mmol)
of D,L-5-( -chlorosulfonylethyl)hydantoin in a
dry ice–acetone bath. The reaction was stirred
until the reactant dissolved. The reaction flask
was removed from the bath and ammonia was
allowed to evaporate in the hood. The white,
gummy product, D,L-homocysteine sulfonamide
hydantoin, was recrystallized from hot water.
Yield: 72%. M.pt. 185–186 C. Thin layer chro-
matography on silica gel with n-butanol/acetic
acid/water (5/2/2) as eluent gave a single spot
(R f 0.54) that was detected by treatment with
chlorine gas followed by spraying with a solution
of toluidine containing KI. One gram of the
product was dissolved in boiling water, then
filtered. The filtrate was stored in a refrigerator at
8 C for 1 week at which time crystals suitable for
X-ray analysis were obtained.
Table 1. Crystal Data and Structure Refinement
Compound
CCDC deposit no.
Color/shape
Empirical formula
Formula weight
Temperature, K
Crystal system
Space group
(C3H3N2O2)(CH2)2SO2NH2
CCDC-1003/6212
clear-colorless/parallelepiped
C5H9N3O4S
207.21
293(2)
Monoclinic
C2/c (No. 15)
˚
Unit cell dimensions
a = 15.653(2) A
˚
b = 9.6489(10) A
˚
c = 11.066(2) A
= 94.64(2)
3
˚
Volume, A
1665.9(4)
Z
8
Density (calculated), g/cm3
Absorption coefficient, mm
1.652
0.376
1
range for data collection, deg
Reflections measured
1.5–23.0
2483
Independent/observed reflections
1158 (Rint = 0.013)/1026
([I > 2 (I)])
1158/0/131
Data/restraints/parameters
Goodness of fit on F2
Final R indices [I > 2 (I)]
R indices (all data)
1.092
R1 = 0.0264, wR2 = 0.0747
R1 = 0.0329, wR2 = 0.0772
0.0060(7)
Extinction coefficient
Max/min transmission
Largest diff. peak and hole
0.999/0.981
0.228, 0.264
Spectroscopy
Infrared spectral data were collected on
a Mattson Cygnus 100 FTIR analyzer using
KBr pellets. Nuclear magnetic resonance spectra
was prepared by modification of the method of
Reisner.3,4 D,L-Homocystine was first protected
as the hydantoin, di-(2,4-imidazolidinedione-5-
Fig. 1. A thermal ellipsoid plot of the title compound illustrating the crystallographic
numbering scheme. Thermal ellipsoids are shown at 40% probability.

2,5-Dioxo-4-imidazolidineethanesulfonamide
279
Table2. AtomicCoordinates(104)andEquivalentIsotropicThermal
---
---
---
---
---
C H CH2 );3.07(m, 2H, C H2 SO2NH2);
Parameters (102)
--- --- ---
2.10 (m, 1H, C H2 CH2 SO2NH2); 1.90 (m,
--- --- ---
1H, C H2 CH2 SO2NH2).
13C NMR:
175.4 (CO); 157.3 (urea
--- --- ---
a
Atom
x
y
z
Ueq
S
1855(1)
493(1)
320(1)
684(1)
799(1)
1529(1)
154(1)
1069(1)
2354(1)
987(1)
980(1)
2462(1)
1107(1)
445(1)
2684(2)
2687(2)
3949(2)
1215(2)
1225(2)
3460(2)
3490(2)
1171(2)
2114(2)
4674(2)
231(2)
7630(1)
5830(2)
4990(2)
4094(2)
6130(2)
7121(2)
4013(2)
5138(2)
6604(2)
5172(1)
3321(1)
8655(1)
7788(2)
36(1)
32(1)
31(1)
31(1)
34(1)
37(1)
33(1)
34(1)
43(1)
46(1)
44(1)
54(1)
53(1)
CO of hydantoin); 56.1 ( C H CH2 ); 50.5
C(1)
C(2)
C(3)
C(4)
C(5)
N(1)
N(2)
N(3)
O(1)
O(2)
O(3)
O(4)
---
---
---
---
---
( C H2 SO2NH2); 26.6 ( C H2 CH2 SO2
NH2).
FAB-MS: molecular ion peak MH+ at 208.
Single-crystal analysis
X-ray measurements were carried out on
an Enraf-Nonius CAD4 automated diffractometer
usingMoK radiation( = 0.71073A). Intensity
˚
1250(2)
data were corrected for Lorentz and polarization
effects after which a semiempirical absorption
correction was applied. The structure was solved
using SHELXTL-PC7 and refined against all F2
datausingSHELXL-97.8 Allnon-hydrogenatoms
were assigned anisotropic displacement parame-
ters. The hydrogen atoms involved in the hydro-
gen bonding network (except H5b) were located
in difference Fourier syntheses; their positional
parameters were refined with fixed isotropic ther-
mal parameters [Uiso(H) = 1.2 Uiso(parent)].
The remaining protons were included in cal-
culated positions and allowed to ride on their
parent carbon atoms with fixed isotropic ther-
mal parameters [Uiso(H) = 1.2 Uiso(C)]. A
summary of experimental data is presented in
Table 1.
aEquivalent isotropic U defined as one third the trace of the orthog-
onalized Ui j tensor.
were recorded on a Bruker DPX-300 MHz with
d6-DMSO as solvent. FAB mass spectra were
obtained in a matrix of glycerol with a Fisons
ProSpec triple sector mass spectrometer equipped
with an LSIMS 40 KV cesium primary gun.
IR(microns): 3.05 , broad, NH of hydan-
toin and sulfonamide; 5.65 , CO of hydantoin;
5.76 , 5.84 , broad, urea CO of hydantoin;
6.48 , NH of SO2NH2; 7.55 , 8.77 , S → O
of SO2NH2.
1H NMR: 10.6 (s, 1H, imide NH of hy-
dantoin); 8.05 (s, 1H, amide NH of hydantoin);
---
6.91 (s, 2H, NH2 of SO2NH2); 4.17 (m, 1H,
˚
Table 3. Selected Geometric Parameters for 1 in (A) and ( )
---
---
---
---
S
C(1) C(2)
C(2) N(1)
---
C(3) N(1)
S
S
O(4)
C(5)
---
1.428(2)
1.769(2)
1.524(3)
1.224(2)
S
O(3)
---
---
1.436(2)
1.455(3)
1.212(2)
1.335(3)
N(3)
---
---
1.591(2)
1.514(3)
1.356(3)
1.390(2)
C(1) N(2)
C(1) C(4)
---
C(3) O(2)
C(2) O(1)
---
C(3) N(2)
---
C(4) C(5)
1.518(3)
--- ---
--- ---
--- ---
S
O(4)
O(4)
S
O(3)
C(5)
---
118.57(10) O(4)
108.48(10) O(3)
S
N(3)
C(5)
---
107.60(11) O(3)
--- ---
106.02(10) N(3) S
114.5(2)
126.1(2)
123.9(2)
113.9(2)
N(3)
C(5)
---
107.21(10)
108.65(10)
111.7(2)
106.5(2)
107.5(2)
112.2(2)
--- ---
--- ---
S
S
---
---
---
N(2) C(1) C(2)
101.6(2)
127.4(2)
128.6(2)
110.9(2)
112.2(2)
74.1(2)
N(2) C(1) C(4)
C(2) C(1) C(4)
--- ---
--- ---
--- ---
O(1) C(2) N(1)
--- ---
O(1) C(2) C(1)
--- ---
N(1) C(2) C(1)
--- ---
O(2) C(3) N(2)
--- ---
O(2) C(3) N(1)
--- ---
N(2) C(3) N(1)
--- ---
C(5) C(4) C(1)
--- ---
C(4) C(5)
S
C(2) N(1) C(3)
C(3) N(2) C(1)
--- ---
---
---
---
---
--- --- ---
C(4) C(5) S N(3)
N(2) C(1) C(4) C(5)
--- --- ---
C(1) C(4) C(5)
S
174.2(1)
44.4(2)
72.5(2)
--- --- ---
C(4) C(5) S O(4)
C(4) C(5)
S
O(3)
172.8(2)

280
Kautz, Chang, Qin, and Trawick
metric space groups. All bond distances are in-
ternally consistent and in agreement with ex-
perimental values found in similar compounds.6
Molecules are in an extended structure as shown
---
---
---
in Fig. 1 with a C(1) C(4) C(5) S torsion an-
gle of 174.2(1) . The atoms in the hydantoin
(imidazolidinedione) ring are planar as expected6
˚
with a mean standard deviation of 0.008 A. Five
of the six bond angles of the sulfonamide group
are within a few degrees of tetrahedral as listed in
--- ---
Table 3 while the O(4) S O(3) was determined
to be 118.57(10) giving the sulfonamide group
distorted tetrahedral geometry.
Figure 2 illustrates the molecular packing ar-
rangement in the unit cell. A three-dimensional
network of intermolecular hydrogen bonding oc-
curs within the crystal lattice involving all of the
---
Fig. 2. A representation of the molecular packing arrange-
ment in the unit cell illustrating the network of intermolecular
interactions.
N H and O atoms of the imidazolidinedione
ring and the sulfonamide functional group. In-
termolecular contact distances are presented in
Table 4. According to the somewhat liberal def-
inition ascribed by Desiraju and Steiner,9 the
Results and discussion
---
C(5) H(5b)
O(1) contact may be described as
The crystallographic data of 1 best fit a mon-
oclinic lattice, space group C2/c (No. 15). The
molecular structure is illustrated in Fig. 1. Atomic
coordinates are tabulated in Table 2 while select
geometric parameters are presented in Table 3.
The title compound contains a hydantoin
ring attached to an ethylsulfonamide chain at
the chiral center [C(1)] of the ring (again see
Fig. 1). Both enantiomers are observed in the
crystal structure, as is required for centrosym-
a weak hydrogen bond.
Acknowledgments
The authors thank Dr. Eric L. Sappenfield for col-
lection of X-ray crystallographic data and Dr. James
Karban for FAB-mass spectra. This work was sup-
ported by the Baylor University Research Committee.
References
Table 4. Analysis of Potential Hydrogen Bonding in 1
1. Meek, T.D.; Villafranca, J.J. Biochemistry 1980, 19, 5513.
2. Masters, D.S.; Meister, A. J. Biol. Chem. 1982, 257, 8711.
3. Reisner, D.B. J. Am. Chem. Soc. 1956, 78, 5102.
4. Mosher, C.W.; Silverstein, R.M.; Crews, O.P.; Baker, B.R.
J. Org. Chem. 1958, 23, 1257.
5. Karabinos, J.V.; Szabo, J.L. J. Am. Chem. Soc. 1944, 66, 649.
6. Mullica, D.F.; Trawick, M.L.; Wu, P.W.N.; Sappenfield, E.L.
J. Chem. Crystallogr. 1998, 28, 761.
7. Siemens SHELXTL-PC, version 5.03; Siemens Analytical
X-ray Instruments; Madison, WI.
8. Sheldrick, G.M. SHELXL-97; University of Go¨ttingen;
Germany.
---
---
H
Atom
---
D
H
H
A
D
A
D
A
N(1) H(1a)
O(2)a
O(3)b
O(2)c
O(1)d
O(1)e
0.78(2) 2.30(2) 3.030(2)
0.85(2) 2.02(2) 2.845(2)
0.81(2) 2.19(3) 2.978(3)
0.84(3) 2.10(3) 2.929(3)
155(2)
165(2)
168(2)
167(2)
156
---
N(2) H(2)
---
N(3) H(3a)
---
N(3) H(3b)
---
C(5) H(5b)
0.97
2.38
3.292(3)
a
x, y, z + 1/2.
x + 1/2, y 1/2, z + 3/2.
b
c
d
e
x + 1/2,
y
1/2, z + 1.
9. Desiraju, G.R.; Steiner, T. The Weak Hydrogen Bond in Struc-
tural Chemistry and Biology; Oxford University Press: New
York, 1999.
x, y, z + 1.
x, y, z + 3/2.