Download citation
Download citation
link to html
In the title compound, C4H5NO3, the morpholine ring adopts a boat conformation that is distorted towards twist-boat, the boat ends being the two Csp3 atoms of the ring. The mol­ecular packing is stabilized by the establishment of strong inter­molecular NH...OC hydrogen bonds, which give rise to centrosymmetric dimers, and a network of weak CH2...OC hydrogen bonds, where each dimer inter­acts with eight neighbouring morpholine­dione rings.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270106010079/ob3002sup1.cif
Contains datablocks morpholinedione, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270106010079/ob3002Isup2.hkl
Contains datablock I

CCDC reference: 609550

Comment top

Recently, there has been much interest in developing biodegradable polymers since they have a wide range of applications in the biomedical field (Huang, 1985). Most of these materials belong to the family of aliphatic polyesters and they are mainly obtained by ring-opening polymerization of lactones such as glycolide and lactide. Poly(ester amides) also constitute a group with potential applications in the above field because of their ability to establish strong intermolecular hydrogen-bond interactions between the amide groups (Montané et al., 2002). These hydrogen bonds may enhance mechanical and thermal properties, whereas degradability may be ensured by the presence of labile ester groups. Polydepsipeptides belong to the family of poly(ester amides) and have an additional interest because they are usually composed of metabolizable α-amino acid and α-hydroxy acid units. These polymers can be synthesized by a ring-opening polymerization reaction of morpholine-2,5-dione derivatives (In't Veld et al., 1990). Furthermore, copolymerization of these rings with lactones such as caprolactone (In't Veld et al., 1992) or glycolide (In't Veld et al., 1994) has been assayed with promising results in order to obtain samples covering a wide range of properties. Despite the growing interest in this class of polymers, data on structures of starting monomers are limited to a few publications. Thus, only the crystalline structures of substituted morpholine-2,5-diones, suc as (3R,6S)-3-benzyl-6-isopropylmorpholine-2,5-dione (Bolte & Egert, 1994), 3-benzyl-3-hydroxy-6-methylamino-6-(2-methylpropyl)morpholine-2,5-dione (Iijima et al., 1992) and (±)-6-benzyl-3,3-dimethylmorpholine-2,5-dione (Linden et al., 2001), have been reported. In this work, we study the structure of the title compound, (I). It is worth noting that this ring has a chemical constitution, which is intermediate between the cyclic dipeptide of glycine (piperazine-2,5-dione) and the glycolide ring.

The molecule of (I) is shown in Fig. 1, and selected torsion angles are given in Table 1. The ester and amide groups are almost planar, with r.m.s. deviations of 0.002 Å for atoms C3, C2, O2 and O1, and 0.046 Å for atoms C6, C5, O5, N4 and C3, from the mean planes passing through them. The cyclic molecule has an irregular skew-boat conformation in which the two indicated planar groups occur. The boat ends are the two Csp3 atoms, which have deviations of 0.322 (1) Å (atom C3) and 0.359 (2) Å (atom C6) from the base of the boat defined by the other four ring atoms. The twist of the ring results from the slight non-planarity of the base atoms, the C3—N4—C5—C6 and C6—O1—C2—C3 torsion angles deviating from 0° (Table 1). The puckering parameters (Cremer & Pople, 1975) are Q = 0.404 (1) Å, θ = 87.9 (2)° and ϕ= 313.1 (2) °, which indicate a conformation midway between boat (ideal values of θ = 90° and ϕ = 60k°, where k is an integer) and twist-boat [θ = 90° and ϕ = (60k + 30)°]. Equivalent ring-puckering parameters were found for (±)-6-benzyl-3,3-dimethylmorpholine-2,5-dione [Q = 0.463 (2) Å, θ = 92.4 (2)° and ϕ = 133.4 (2)°] and (3R,6S)-3-benzyl-6-isopropylmorpholine-2,5-dione [Q = 0.494 (2) Å, θ = 93.1 (2)° and ϕ = 129.3 (2)°] (Linden et al., 2001), whereas an almost completely flat boat was found for the other substituted morpholine ring compound that has been studied so far (Iijima et al., 1992). This is the only studied compound that has substituted groups on both Csp3 atoms.

In (I), the NH group forms an intermolecular hydrogen bond with the amide O atom of an adjacent molecule (Table 2). This acceptor molecule then donates back to the first molecule, thereby linking pairs of molecules into centrosymmetric dimers whose interactions can be described by the graph-set motif R22(8) (Bernstein et al., 1995). These interactions were found in the previously studied morpholinodiones and explained in detail for (±)-6-benzyl-3,3-dimethylmorpholine-2,5-dione (Linden et al., 2001).

The molecular packing of (I) is also characterized by the establishment of weak hydrogen-bond interactions between CH2 and CO groups (Table 2). In this way, the ester carbonyl group of a morpholinedione ring forms a bifurcated hydrogen bond with the glycolidyl H atoms of two neighbouring rings. Furthermore, each glycolidyl H atom of the former ring interacts with the carbonyl ester group of a different neighbouring molecule. Note that similar and short H···O distances are found (2.48 and 2.40 Å). These interactions were not reported for the previously studied morpholine-2,5-diones, which comprised mono- or disubstituted glycolidyl units. However, weak C—H···O intermolecular hydrogen bonds playing a decisive role in the crystal organization were also found in the related glycolide ring (Belen'kaya et al., 1997) and indeed in the lactide ring (van Hummel et al., 1982; Belen'kaya et al., 1997), the H···O distances being within the 2.33–2.44 Å range.

Experimental top

Compound (I) was synthesized by the cyclization reaction of the N-chloroacetylglycine sodium salt performed under the conditions reported previously (In't Veld et al., 1994). Basically, the reaction was carried out under vacuum and using celite and Sb2O3 as adsorbent and catalysts, respectively. The temperature of reaction was maintained at 423 K for 2 h and then at 488 K for 4 h. A yellow solid sublimed and was recrystallized from acetonitrile to give colourless prismatic crystals (yield 32%, m.p. 466 K). 1H NMR (DMSO): δ 8.34 (b, 1H, NH), 4.65 (s, 2H, OCH2), 4.00 (d, 2H, NHCH2). 13C NMR (DMSO): δ 166.84 (CONH), 165.84 (COO), 67.89 (COOCH2), 42.73 (CONHCH2). IR (KBr, ν, cm−1): 2932 (CH2), 1748 (CO, ester), 1694 (amide I), 1436 (amide II), 1265 (C—O—C).

Refinement top

The amide H atom was located in difference Fourier map and refined isotropically. The remaining H atoms were placed in calculated positions, with C—H = 0.97 Å, and treated as riding on their attached C atoms. The Uiso parameters of the two H atoms of each CH2 group were refined as free variables.

Computing details top

Data collection: CAD-4 Software (Kiers, 1994); cell refinement: CAD-4 Software; data reduction: WinGX-PC (Farrugia, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976) and PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 and WinGX-PC.

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. The molecular packing of (I). The dashed lines indicate hydrogen bonds.
morpholine-2,5-dione top
Crystal data top
C4H5NO3F(000) = 240
Mr = 115.09Dx = 1.575 Mg m3
Monoclinic, P21/nMelting point = 192–193 K
Hall symbol: -P 2ynMo Kα radiation, λ = 0.71073 Å
a = 5.379 (5) ÅCell parameters from 25 reflections
b = 9.218 (2) Åθ = 10–22°
c = 9.794 (2) ŵ = 0.14 mm1
β = 92.28 (4)°T = 293 K
V = 485.2 (5) Å3Needle, colourless
Z = 40.60 × 0.14 × 0.10 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer
Rint = 0.012
Radiation source: fine-focus sealed tubeθmax = 30.0°, θmin = 3.0°
Graphite monochromatorh = 77
ω scansk = 012
1471 measured reflectionsl = 013
1406 independent reflections1 standard reflections every 120 min
1139 reflections with I > 2σ(I) intensity decay: none
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.044Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.130H atoms treated by a mixture of independent and constrained refinement
S = 1.05 w = 1/[σ2(Fo2) + (0.0732P)2 + 0.1054P]
where P = (Fo2 + 2Fc2)/3
1406 reflections(Δ/σ)max < 0.001
79 parametersΔρmax = 0.30 e Å3
0 restraintsΔρmin = 0.25 e Å3
Crystal data top
C4H5NO3V = 485.2 (5) Å3
Mr = 115.09Z = 4
Monoclinic, P21/nMo Kα radiation
a = 5.379 (5) ŵ = 0.14 mm1
b = 9.218 (2) ÅT = 293 K
c = 9.794 (2) Å0.60 × 0.14 × 0.10 mm
β = 92.28 (4)°
Data collection top
Enraf–Nonius CAD-4
diffractometer
Rint = 0.012
1471 measured reflections1 standard reflections every 120 min
1406 independent reflections intensity decay: none
1139 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0440 restraints
wR(F2) = 0.130H atoms treated by a mixture of independent and constrained refinement
S = 1.05Δρmax = 0.30 e Å3
1406 reflectionsΔρmin = 0.25 e Å3
79 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)

1.8913 (0.0045) x + 6.0123 (0.0068) y + 6.4349 (0.0078) z = 7.1722 (0.0070)

* −0.0540 (0.0007) O2 * 0.0113 (0.0011) C2 * 0.0898 (0.0010) O1 * 0.0197 (0.0004) C3 * −0.0668 (0.0007) C6

Rms deviation of fitted atoms = 0.0565

3.7933 (0.0172) x + 4.1671 (0.0076) y + 5.0703 (0.0370) z = 4.9836 (0.0212)

Angle to previous plane (with approximate e.s.d.) = 24.55 (0.30)

* 0.0157 (0.0020) C5 * −0.0416 (0.0034) O5 * 0.0097 (0.0056) C6 * 0.0767 (0.0058) N4 * −0.0091 (0.0090) H4 * −0.0514 (0.0033) C3

Rms deviation of fitted atoms = 0.0422

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.15816 (16)0.81416 (12)0.32136 (10)0.0371 (3)
O20.26093 (19)0.62421 (13)0.44628 (12)0.0440 (3)
O50.3407 (2)1.06943 (12)0.35065 (11)0.0451 (3)
N40.25311 (19)0.86708 (12)0.47476 (12)0.0322 (3)
H40.373 (4)0.887 (2)0.531 (2)0.054 (5)*
C20.1074 (2)0.71558 (14)0.41619 (13)0.0301 (3)
C30.1398 (2)0.72367 (15)0.48259 (15)0.0354 (3)
H310.25250.65410.43890.051 (4)*
H320.11720.69620.57790.051 (4)*
C50.2249 (2)0.95467 (14)0.36962 (13)0.0300 (3)
C60.0382 (3)0.90722 (17)0.26778 (14)0.0393 (3)
H610.12630.85680.19360.057 (4)*
H620.03670.99310.22960.057 (4)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0264 (4)0.0446 (6)0.0413 (5)0.0069 (4)0.0131 (4)0.0055 (4)
O20.0336 (5)0.0463 (6)0.0523 (6)0.0157 (4)0.0061 (4)0.0023 (5)
O50.0436 (6)0.0410 (6)0.0520 (6)0.0159 (5)0.0159 (5)0.0115 (5)
N40.0257 (5)0.0331 (6)0.0388 (6)0.0068 (4)0.0128 (4)0.0036 (4)
C20.0244 (5)0.0330 (6)0.0332 (6)0.0030 (4)0.0041 (4)0.0040 (5)
C30.0269 (6)0.0319 (6)0.0482 (8)0.0051 (5)0.0130 (5)0.0069 (5)
C50.0239 (5)0.0323 (6)0.0339 (6)0.0027 (4)0.0045 (4)0.0000 (5)
C60.0392 (7)0.0460 (8)0.0336 (6)0.0138 (6)0.0120 (5)0.0065 (6)
Geometric parameters (Å, º) top
O1—C21.3353 (17)C2—C31.505 (2)
O1—C61.4431 (18)C5—C61.5080 (19)
N4—C51.3221 (17)C3—H310.9700
N4—C31.4565 (17)C3—H320.9700
N4—H40.88 (2)C6—H610.9700
O2—C21.2079 (17)C6—H620.9700
O5—C51.2380 (16)
C2—O1—C6119.37 (11)N4—C3—H31108.9
C5—N4—C3122.31 (11)C2—C3—H31108.9
C5—N4—H4117.8 (13)N4—C3—H32108.9
C3—N4—H4118.2 (14)C2—C3—H32108.9
O2—C2—O1119.17 (12)H31—C3—H32107.7
O2—C2—C3122.43 (13)O1—C6—C5115.39 (11)
O1—C2—C3118.39 (11)O1—C6—H61108.4
O5—C5—N4124.47 (12)C5—C6—H61108.4
O5—C5—C6119.54 (12)O1—C6—H62108.4
N4—C5—C6115.99 (11)C5—C6—H62108.4
N4—C3—C2113.40 (11)H61—C6—H62107.5
C6—O1—C2—O2169.25 (13)O2—C2—C3—N4157.07 (13)
C6—O1—C2—C311.27 (18)O1—C2—C3—N422.40 (18)
C3—N4—C5—O5170.93 (13)C2—O1—C6—C536.48 (19)
C3—N4—C5—C68.71 (19)O5—C5—C6—O1154.23 (14)
C5—N4—C3—C233.13 (19)N4—C5—C6—O126.12 (19)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N4—H4···O5i0.88 (2)2.01 (2)2.888 (2)177 (2)
C6—H61···O2ii0.972.483.301 (2)142
C6—H62···O2iii0.972.403.297 (2)153
Symmetry codes: (i) x1, y+2, z+1; (ii) x1/2, y+3/2, z1/2; (iii) x+1/2, y+1/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC4H5NO3
Mr115.09
Crystal system, space groupMonoclinic, P21/n
Temperature (K)293
a, b, c (Å)5.379 (5), 9.218 (2), 9.794 (2)
β (°) 92.28 (4)
V3)485.2 (5)
Z4
Radiation typeMo Kα
µ (mm1)0.14
Crystal size (mm)0.60 × 0.14 × 0.10
Data collection
DiffractometerEnraf–Nonius CAD-4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
1471, 1406, 1139
Rint0.012
(sin θ/λ)max1)0.703
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.044, 0.130, 1.05
No. of reflections1406
No. of parameters79
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.30, 0.25

Computer programs: CAD-4 Software (Kiers, 1994), CAD-4 Software, WinGX-PC (Farrugia, 1999), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEPII (Johnson, 1976) and PLATON (Spek, 2003), SHELXL97 and WinGX-PC.

Selected torsion angles (º) top
C6—O1—C2—C311.27 (18)O1—C2—C3—N422.40 (18)
C3—N4—C5—C68.71 (19)C2—O1—C6—C536.48 (19)
C5—N4—C3—C233.13 (19)N4—C5—C6—O126.12 (19)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N4—H4···O5i0.88 (2)2.01 (2)2.888 (2)177 (2)
C6—H61···O2ii0.972.483.301 (2)142
C6—H62···O2iii0.972.403.297 (2)153
Symmetry codes: (i) x1, y+2, z+1; (ii) x1/2, y+3/2, z1/2; (iii) x+1/2, y+1/2, z+1/2.
 

Follow Acta Cryst. C
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds