(2S)-1-Carbamoylpyrrolidine-2-carboxylic acid

Article abstract of DOI:10.1107/S0108270107014102

In the title compound, also known as N-carbamoyl-l-proline, C6H10N2O3, the pyrrolidine ring adopts a half-chair conformation, whereas the carboxyl group and the mean plane of the ureide group form an angle of 80.1 (2)°. Mol-ecules are joined by N - H...O and O - H...O hydrogen bonds into cyclic structures with graph-set R ² 2(8), forming chains in the b-axis direction that are further connected via N - H...O hydrogen bonds into a three-dimensional network. International Union of Crystallography 2007.

Full text of DOI:10.1107/S0108270107014102

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
crystallizes in a zwitterionic form]; this is the result of a
resonance effect in the ureide unit, which causes a diminution
in the nucleophilic character of the N atoms, and makes it
impossible for this atom to withdraw the acidic H atom of the
ISSN 0108-2701
(2S)-1-Carbamoylpyrrolidine-
2-carboxylic acid
a
a
a
Â
Luis E. Seijas, Gerzon E. Delgado, * Asiloe J. Mora, Ali
Bahsasb and Alexander Bricenoc
Ä
a
Â
Â
Laboratorio de Cristalografõa, Facultad de Ciencias, Departamento de Quõmica,
carboxyl group. The neutral character of the compound is
con®rmed by the clear difference of the values for the O1ÐC5
and O2ÐC5 bond distances (Table 1). The carboxyl group is
axial to the pyrrolidine ring, forming an angle of 82.9 (2)ꢀ. This
value matches that observed in (I) (Kayushina & Vainshtein,
1965). However, this group adopts a different orientation in
(II), with an O2ÐC5ÐC4ÐN1 torsion angle of 33.8 (3)ꢀ
compared with 6.9 (5)ꢀ in (I). The ureide group is equatorial
and almost coplanar with atoms C1, N1 and C4, forming an
angle of 5.4 (2)ꢀ with the average plane of the pyrrolidine ring.
The intercepting angle between the average planes of the two
functional groups is 80.1 (2)ꢀ. This value differs from that
observed in two N-carbamoyl derivatives of ꢀ-amino acids
reported in the Cambridge Structural Database (CSD; Allen,
2002), viz. N-carbamoyl-l-asparagine (CSD refcode
GEMZED; Yennawar & Viswamitra, 1988) and N-carbamoyl-
dl-aspartic acid (BERBOP01; Zvargulis & Hambley, 1994),
which have intercepting angles of 155.0 (3) and 164.2 (5)ꢀ,
respectively. This difference with compound (II) is due to the
fact that here the Cꢀ atom belongs to a pyrrolidine ring,
forcing the two substituent groups (carboxyl and ureide) to
form a more acute intercepting angle. The asymmetry para-
meters ÁC2 [maximum = +41.5 (4)ꢀ, minimum = +0.5 (4)ꢀ],
ÁCs [maximum = +33.4 (4)ꢀ, minimum = +27.2 (4)ꢀ], ÁC2(N1)
= 0.5 (4)ꢀ and ÁC2(C2ÐC3) = 0.5 (4)ꢀ reveal the presence of a
twofold axis through N1 and bisecting the C2ÐC3 bond,
Universidad de Los Andes, Merida 5101, Venezuela, bLaboratorio de Resonancia
Â
Â
Â
Magnetica Nuclear, Facultad de Ciencias, Departamento de Quõmica, Universidad
c
Â
Â
de Los Andes, Merida 5101, Venezuela, and Laboratorio de Sõntesis y Caracteriza-
Â
cion de Nuevos Materiales, IVIC, Venezuela
Correspondence e-mail: gerzon@ula.ve
Received 12 March 2007
Accepted 23 March 2007
Online 21 April 2007
In the title compound, also known as N-carbamoyl-l-proline,
C6H10N2O3, the pyrrolidine ring adopts a half-chair conforma-
tion, whereas the carboxyl group and the mean plane of the
ureide group form an angle of 80.1 (2)ꢀ. Molecules are joined
by NÐHÁ Á ÁO and OÐHÁ Á ÁO hydrogen bonds into cyclic
structures with graph-set R22(8), forming chains in the b-axis
direction that are further connected via NÐHÁ Á ÁO hydrogen
bonds into a three-dimensional network.
Comment
N-Carbamoyl derivatives of ꢀ-amino acids are compounds
closely related to biochemical processes of great importance,
for example, the biosynthesis of pyrimidine nucleotides (van
Kuilenburg et al., 2004), which are essential in a number of
biochemical processes, such as the synthesis of RNA, DNA
and phospholipids and glycosylation of proteins (Huang &
Graves, 2003). In addition, in recent years there has been an
increasing interest in the industrial use of N-carbamoyl
compounds, since natural and non-natural amino acids can be
obtained through an enantioselective enzymatic reaction
(Chen et al., 2003; Altenbuchner et al., 2001; Burton &
Dorrington, 2004). Wang et al. (2001) modeled the enzyme±
substrate interaction in the complex DNCAase-N-carbamoyl-
d-p-hydroxyphenylglycine; they concluded that the substrate
speci®city in the enzyme±substrate complex is essentially due
to hydrogen bonds formed between the carboxyl and ureide
groups of the N-carbamoyl and the side groups of the amino
acid units in the active site of the enzyme, acting as anchors to
®x and orient the substrate and facilitating the amido-
hydrolytic reaction. We present here the crystal structure of a
new compound, namely N-carbamoyl-l-proline, (II).
Figure 1
Fig. 1 shows the molecular structure and the atom-labelling
scheme. N-Carbamoyl-l-proline crystallizes in a neutral form
[unlike l-proline, (I) (Kayushina & Vainshtein, 1965), which
View of N-carbamoyl-l-proline with the atom-labelling scheme. Displa-
cement ellipsoids are drawn at the 50% probability level and H atoms are
shown with an arbitrary radius.
Acta Cryst. (2007). C63, o303±o305
DOI: 10.1107/S0108270107014102
# 2007 International Union of Crystallography o303

organic compounds
which indicates that the pyrrolidine ring adopts a half-chair
conformation (Grif®n et al., 1984; Cremer & Pople, 1975). This
conformation is also observed in the structures of l-proline
(PROLIN; Kayushina
& Vainshtein, 1965), dl-proline
(QANRUT; Myung et al., 2005), l-proline monohydrate
(RUWGEV; Janczak & Luger, 1997) and dl-proline mono-
hydrate (DLPROM02; Flaig et al., 2002).
The crystalline structure is stabilized by three hydrogen
bonds, which involve the carboxyl and ureide groups in the
molecule, serving as both acceptors and donors in a set of
head-to-tail interactions, as depicted in Fig. 2. The geometrical
parameters of these hydrogen bonds are summarized in
1
Table 2. The O2ÐH2Á Á ÁO3( x, y
,
z + 32 ) and N2Ð
2
H2AÁ Á ÁO1( x, y + 12, z + 23 ) hydrogen bonds form rings with
graph set R22(8) (Bernstein et al., 1995). In these interactions,
the O2Á Á ÁO3 distance is markedly different from N2Á Á ÁO1.
The presence of the two N atoms in the ureide group affords a
better hydrogen-bond acceptor capacity to the carbonyl group
O3. Atom O1 acts as a bifurcated acceptor for two NÐHÁ Á ÁO
hydrogen bonds originating from two different molecules, with
graph set C21(4). The R22(8) sets join into zigzag molecular
chains running along the b axis with graph set R22(8)C(7)
(Fig. 3). This graph set is also observed in the N-carbamoyl ꢀ-
amino acids GEMZED (Yennawar & Viswamitra, 1988) and
BERBOP01 (Zvargulis & Hambley, 1994). The zigzag chains
are connected laterally by N2ÐH2BÁ Á ÁO1( x + 12, y, z + 21 )
Figure 3
A partial packing view of (II). Broken lines indicate hydrogen bonds. H
atoms not involved in hydrogen bonding have been omitted for clarity.
Experimental
hydrogen bonds, which generates
network.
a three-dimensional
l-Proline (500 mg, 4.3 mmol) was dissolved in 20 ml of water and the
solution was acidi®ed with concentrated HCl (37% v/v) to pH 5.
KOCN (1050 mg, 12.9 mmol) was then added to this solution. The
mixture was warmed, with agitation, to 333 K over a period of 4 h.
The resulting solution was cooled to room temperature and acidi®ed
with concentrated HCl (37% v/v) to pH 4, at which point a white solid
precipitated. The solid was ®ltered off and washed with cool water
(yield 421 mg, 62%; m.p. 476±477 K). The solid was recrystallized
from a mixture of methanol and water (2:1), producing colourless
crystals with a rectangular form. FT±IR (cm 1): 1695.5 [t, C O (acid
group)], 1660.8 [t, C O (ureide group)]. 1H NMR (400 MHz,
DMSO-d6): ꢁ 12.45 (H2, bs), 5.88 (H2A = H2B, s), 4.14 (H4, dd), 3.32
(H1B, m), 3.23 (H1A, m), 1.84 (H3A, m), 2.06 (H3B, m), 1.84 (H2C,
H2D, m); 13C NMR (100.6 MHz, DMSO-d6): ꢁ 174.7 (C5), 157.2 (C6),
58.4 (C4), 46.4 (C1), 29.6 (C3), 24.4 (C2).
Crystal data
3
Ê
C6H10N2O3
Mr = 158.16
Orthorhombic, P212121
V = 792.7 (3) A
Z = 4
Mo Kꢀ radiation
1
Ê
a = 6.4711 (13) A
ꢂ = 0.11 mm
T = 298 (2) K
Ê
b = 9.781 (2) A
Ê
c = 12.524 (3) A
0.50 Â 0.20 Â 0.10 mm
Data collection
Rigaku AFC-7S Mercury
diffractometer
Absorption correction: multi-scan
(Jacobson, 1998)
Tmin = 0.978, Tmax = 0.988
9201 measured re¯ections
952 independent re¯ections
815 re¯ections with I > 2ꢃ(I)
Rint = 0.031
Re®nement
Figure 2
Intermolecular hydrogen bonds in N-carbamoyl-l-proline. Broken lines
R[F2 > 2ꢃ(F2)] = 0.048
wR(F2) = 0.132
S = 1.05
100 parameters
H-atom parameters constrained
indicate hydrogen bonds. H atoms not involved in hydrogen bonding
z + 32; (ii)
1
2
3
Ê
have been omitted for clarity. [Symmetry codes: (i) x, y
x + , y, z 12.]
,
Áꢄmax = 0.17 e A
3
1
2
Ê
0.22 e A
952 re¯ections
Áꢄmin
=
ꢁ
o304 Seijas et al. C6H10N2O3
Acta Cryst. (2007). C63, o303±o305

organic compounds
Table 1
Selected geometric parameters (A, ).
to prepare material for publication: SHELXL97 and PLATON
(Spek, 2003).
ꢀ
Ê
O1ÐC5
O2ÐC5
O3ÐC6
N1ÐC6
N1ÐC4
N1ÐC1
1.215 (3)
1.300 (3)
1.265 (3)
1.337 (4)
1.455 (4)
1.462 (4)
N2ÐC6
C1ÐC2
C2ÐC3
C3ÐC4
C4ÐC5
1.327 (4)
1.503 (5)
1.452 (6)
1.542 (5)
1.513 (4)
This work was supported by CDCHT±ULA (grants Nos.
C-1416-06-08-B and C-1417-06-08-F) and FONACIT (grant
No. LAB-97000821).
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: SK3108). Services for accessing these data are
described at the back of the journal.
C6ÐN1ÐC4
C6ÐN1ÐC1
C4ÐN1ÐC1
N1ÐC1ÐC2
C3ÐC2ÐC1
C2ÐC3ÐC4
N1ÐC4ÐC5
N1ÐC4ÐC3
119.6 (2)
126.4 (3)
113.9 (3)
102.6 (3)
108.0 (3)
105.9 (3)
113.2 (2)
102.3 (3)
C5ÐC4ÐC3
O3ÐC6ÐN2
O3ÐC6ÐN1
N2ÐC6ÐN1
O1ÐC5ÐO2
O1ÐC5ÐC4
O2ÐC5ÐC4
112.5 (3)
121.4 (3)
119.4 (3)
119.3 (3)
124.0 (3)
121.0 (3)
115.0 (2)
References
Allen, F. H. (2002). Acta Cryst. B58, 380±388.
Altenbuchner, J., Siemann-Herzberg, M. & Syldatk, C. (2001). Chem. Bio-
technol. 12, 559±563.
Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem.
Int. Ed. Engl. 34, 1555±1573.
Brandenburg, K. (2001). DIAMOND. Version 2.1e. Crystal Impact GbR,
Bonn, Germany.
Table 2
Hydrogen-bond geometry (A, ).
ꢀ
Ê
Burton, S. & Dorrington, R. A. (2004). Tetrahedron Asymmetry, 15, 2737±
2741.
Chen, H., Ho, C., Liu, J., Lin, K., Wang, Y., Lu, Ch. & Liu, H. (2003).
Biotechnol. Prog. 19, 864±873.
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354±1358.
Flaig, R., Koritsanszky, T., Dittrich, B., Wagner, A. & Luger, P. (2002). J. Am.
Chem. Soc. 124, 3407±3417.
Grif®n, J. F., Duax, W. & Weeks, M. (1984). Atlas of Steriod Structure. New
York: Plenum Publishing Corporation.
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
O2ÐH2Á Á ÁO3i
0.82
0.86
0.86
1.73
2.08
2.13
2.536 (3)
2.914 (4)
2.901 (3)
167
165
149
N2ÐH2AÁ Á ÁO1iii
N2ÐH2BÁ Á ÁO1ii
1
2
Symmetry codes: (i) x; y
;
z ‡ 32; (ii) x ‡ 21; y; z ‡ 21; (iii) x; y ‡ 21; z ‡ 32.
Huang, M. & Graves, L. M. (2003). Cell. Mol. Life Sci. 60, 321±336.
Jacobson, R. (1998). Private communication to the Rigaku Corporation,
Tokyo, Japan.
H atoms of the pyrrolidine ring were positioned geometrically and
Ê
allowed to ride on their respective parent atoms [CÐH = 0.97±0.98 A
and Uiso(H) = 1.2Ueq(parent)]. The H atoms of the ureide group were
positioned geometrically in the plane of the nearest substituent on
the N atom and allowed to ride on their respective parent atoms, with
Janczak, J. & Luger, P. (1997). Acta Cryst. C53, 1954±1956.
Kayushina, R. L. & Vainshtein, B. K. (1965). Kristallogra®ya, 10, 833±835. (In
Russian.)
Kuilenburg, A. B. P. van, van Lenthe, H., Lof¯er, M. & van Gennip, A. H.
(2004). Clin. Chem. 50, 2117±2124.
Ê
NÐH bond lengths of 0.86 A and isotropic displacement parameters
equal to 1.2Ueq(parent). The H atom in the carboxyl group was
positioned geometrically as an idealized OH group, with an OÐH
Ê
bond length of 0.82 A and an isotropic displacement parameter equal
Myung, S., Pink, M., Baik, M.-H. & Clemmer, D. E. (2005). Acta Cryst. C61,
o506±o508.
Rigaku (2000). CrystalClear. Version 1.3.6. Rigaku Corporation, Tokyo,
Japan.
Rigaku/MSC (2004). CrystalStructure. Version 3.6.0. Rigaku/MSC, The Wood-
lands, Texas, USA.
Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of
to 1.5Ueq(O2). The absolute structure was assigned from the known
con®guration of l-proline.
Data collection: CrystalClear (Rigaku, 2000); cell re®nement:
CrystalClear; data reduction: CrystalStructure (Rigaku/MSC, 2004);
program(s) used to solve structure: SHELXS97 (Sheldrick, 1997);
program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997);
molecular graphics: DIAMOND (Brandenburg, 2001); software used
È
Gottingen, Germany.
Spek, A. L. (2003). J. Appl. Cryst. 36, 7±13.
Wang, W., Hsu, W., Chien, F. & Chen, C. (2001). J. Mol. Biol. 306, 251±261.
Yennawar, H. P. & Viswamitra, M. A. (1988). Acta Cryst. C44, 718±720.
Zvargulis, E. S. & Hambley, T. W. (1994). Acta Cryst. C50, 2058±2060.
ꢁ
Acta Cryst. (2007). C63, o303±o305
Seijas et al. C6H10N2O3 o305