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The title compound, C9H16N2O2S, was synthesized from L-me­thionine. The pyrrolidinone ring has an envelope conformation. Molecules are connected into two-dimensional layers by two independent intermolecular N—H...O hydrogen bonds, with N...O distances of 2.939 (5) and 2.914 (5) Å.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536803016374/lh6082sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536803016374/lh6082Isup2.hkl
Contains datablock I

CCDC reference: 222859

Key indicators

  • Single-crystal X-ray study
  • T = 273 K
  • Mean [sigma](C-C) = 0.006 Å
  • R factor = 0.062
  • wR factor = 0.120
  • Data-to-parameter ratio = 16.0

checkCIF/PLATON results

No syntax errors found



Alert level A PLAT761_ALERT_1_A CIF Contains no X-H Bonds .................... ? PLAT762_ALERT_1_A CIF Contains no X-Y-H or H-Y-H Angles ........ ?
Alert level C PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical ? PLAT220_ALERT_2_C Large Non-Solvent C Ueq(max)/Ueq(min) . 2.51 Ratio PLAT222_ALERT_3_C Large Non-Solvent H Ueq(max)/Ueq(min) . 3.09 Ratio PLAT340_ALERT_3_C Low Bond Precision on C-C bonds (x 1000) Ang.. 6
Alert level G REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is correct. If it is not, please give the correct count in the _publ_section_exptl_refinement section of the submitted CIF. From the CIF: _diffrn_reflns_theta_max 25.02 From the CIF: _reflns_number_total 2047 Count of symmetry unique reflns 1218 Completeness (_total/calc) 168.06% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 829 Fraction of Friedel pairs measured 0.681 Are heavy atom types Z>Si present yes
2 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 4 ALERT level C = Check and explain 1 ALERT level G = General alerts; check 3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 1 ALERT type 2 Indicator that the structure model may be wrong or deficient 2 ALERT type 3 Indicator that the structure quality may be low 1 ALERT type 4 Improvement, methodology, query or suggestion

Comment top

Levetiracetam [(S)-α-ethyl-2-oxopyrrolidine acetamide, LEV] is an ethyl analogue of the nootropic drug piracetam. LEV is a new antiepileptic drug (AED) (Bialer et al., 1999) recently approved by the US Food and Drug Administration. LEV possesses a chiral center but only the (S) enantiomer of α-ethyl-2-oxo-pyrrolidine acetylamide has anticonvulsant activity, and therefore it is administered as a single enantiomer (Haria & Balfour, 1997). The title compound, (I), is an intermediate in the synthesis of LEV, and the molecular structure is illustrated in Fig. 1.

Atom C6 is chiral, and it has a (S) configuration. The molecule consists of a pyrrolidinone ring (N1/C1/C2/C3/C4), which has an envelope conformation. Atoms N1/C4/C2/C1 are nearly planar and the mean deviation from this plane is 0.008 (3) Å. Atom C3 is 0.306 (2) Å from this plane and forms the flap of the envelope. The dihedral angle between the N1/C4/C2/C1 mean plane and the C2/C3/C4 plane is 160.7 (2)°. The conformation of the rest of the molecule can be described by a series of dihedral angles. Atoms S1/C8/C7/C6 are nearly planar and the mean deviation from this plane is 0.025 (3) Å. The dihedral angle between the N1/C4/C2/C1 and S1/C8/C7/C6 planes is 91.3 (3)°. The dihedral angle between the N1/C4/C2/C1 and N2/C5/C6 planes is 100.1 (2)° and the dihedral angle between the S1/C8/C7/C6 and N2/C5/C6 planes is 34.7 (3)°.

In the crystal structure of (I), molecules are connected into two-dimensional layers, which are approximately perpendicular to the c axis, by two independent intermolecular N—H···O hydrogen bonds, namely N2—H2C···O2i [symmetry code: (i) 1/2 + x, 5/2 − y, 1 − z], with an N···O = 2.939 (5) Å, H···O = 2.09 Å and N—H···O = 170°, and also N2—H2D···O1ii [symmetry code: (ii) 1/2 − x, 3/2 − y, 1 − z], with N···O = 2.914 (5) Å, H···O = 2.12 Å and N—H···O = 153 Å (see Fig. 2). There is also a questionable intramolecular N—H···N hydrogen bond [N2···N1 = 2.748 (5) Å, H2D···N1 = 2.38 Å and N2—H2D···N1 = 107°].

Experimental top

The title compoud was prepared according to a previously published method (Cossement et al., 1990) from L-methionine. L-Methionine was esterified to its methyl ester using absolute methanol and thionyl chloride. The resulting L-methionine methyl ester hydrochloride was amidated using gaseous ammonia to give L-methionine amide. This amide (50.0 mmol) was treated with potassium hydroxide (14.0 g), tetrabutylammonium bromide (2.5 mmol) and 4-chlorobutyryl chloride (55.0 mmol) in dichloromethane to yield (S)-α-[2-(methylthio)ethyl]-2-oxo-pyrrolidine acetylamide. The reaction mixture was filtered and the filtrate evaporated under reduced pressure. The residue was purified by column chromatography over silica (eluent: mixture of dichloromethane/methanol/ammonia 95.5:4.5:0.2, v/v/v). The resulting white power was dissolved in 60 ml dichloromethane/methanol (13:1, v/v). A single-crystal of the title compound, suitable for X-ray analysis, was grown by slow evaporation of the solvent. [α]25D +36.5° (c = 1 in methanol); 1H NMR (CDCl3, p.p.m.): 1.85 (2H, m), 2.03 (3H, m), 2.12 (2H, m), 2.24 (2H, m), 2.69 (2H, m), 3.44 (2H, m); 13C NMR (CDCl3): 15.50 (CH2), 18.10 (CH3), 27.40 (CH2), 30.45 (CH2), 31.03 (CH2).

Refinement top

H atoms were placed in idealized calculated positions with C—H distances ranging from 0.96 to 0.98 Å and N—H distances of 0.86 Å. They were included in the refinement in riding-motion approximation with Uiso = 1.2Ueq (1.5Ueq for methyl) of the carrier atom.

Computing details top

Data collection: SMART (Bruker, 1997); cell refinement: SMART; data reduction: SAINT (Bruker, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1997); software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), drawn with 30% probability ellipsoids.
[Figure 2] Fig. 2. The crystal packing diagram of (I), viewed along the a axis. Hydrogen bonding is indicated by dasked lines and the following are the atom colour codes: green S, red O, blue N, black C and white H.
(I) top
Crystal data top
C9H16N2O2SF(000) = 464
Mr = 216.30Dx = 1.237 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 687 reflections
a = 7.018 (6) Åθ = 2.6–22.4°
b = 8.818 (7) ŵ = 0.26 mm1
c = 18.760 (16) ÅT = 273 K
V = 1161.0 (17) Å3Plate, colourless
Z = 40.30 × 0.25 × 0.20 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
2047 independent reflections
Radiation source: fine-focus sealed tube1574 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.047
ϕ and ω scansθmax = 25.0°, θmin = 2.2°
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
h = 87
Tmin = 0.927, Tmax = 0.950k = 1010
4477 measured reflectionsl = 2217
Refinement top
Refinement on F2H-atom parameters constrained
Least-squares matrix: full w = 1/[σ2(Fo2) + (0.084P)2]
where P = (Fo2 + 2Fc2)/3
R[F2 > 2σ(F2)] = 0.062(Δ/σ)max = 0.002
wR(F2) = 0.120Δρmax = 0.25 e Å3
S = 1.08Δρmin = 0.20 e Å3
2047 reflectionsAbsolute structure: (Flack, 1983), 830 Friedel pairs
128 parametersAbsolute structure parameter: 0.02 (17)
0 restraints
Crystal data top
C9H16N2O2SV = 1161.0 (17) Å3
Mr = 216.30Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 7.018 (6) ŵ = 0.26 mm1
b = 8.818 (7) ÅT = 273 K
c = 18.760 (16) Å0.30 × 0.25 × 0.20 mm
Data collection top
Bruker SMART CCD area-detector
diffractometer
2047 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
1574 reflections with I > 2σ(I)
Tmin = 0.927, Tmax = 0.950Rint = 0.047
4477 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.062H-atom parameters constrained
wR(F2) = 0.120Δρmax = 0.25 e Å3
S = 1.08Δρmin = 0.20 e Å3
2047 reflectionsAbsolute structure: (Flack, 1983), 830 Friedel pairs
128 parametersAbsolute structure parameter: 0.02 (17)
0 restraints
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.

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
C10.3367 (5)0.7672 (4)0.5660 (2)0.0341 (9)
C20.4175 (7)0.6368 (4)0.6083 (2)0.0458 (11)
H2A0.47730.56330.57700.055*
H2B0.31820.58660.63540.055*
C30.5637 (7)0.7081 (5)0.6577 (3)0.0577 (13)
H3A0.69170.69260.63960.069*
H3B0.55510.66460.70510.069*
C40.5145 (7)0.8769 (4)0.6593 (2)0.0461 (11)
H4A0.44350.90240.70200.055*
H4B0.62890.93850.65750.055*
C50.5068 (6)1.1382 (4)0.5376 (2)0.0300 (9)
C60.3400 (6)1.0488 (4)0.5705 (2)0.0289 (9)
H60.24711.03210.53230.035*
C70.2383 (5)1.1415 (4)0.6287 (2)0.0353 (10)
H7A0.32191.15070.66960.042*
H7B0.21371.24280.61070.042*
C80.0515 (6)1.0707 (4)0.6522 (2)0.0422 (11)
H8A0.07760.97210.67300.051*
H8B0.02821.05510.61070.051*
C90.1426 (8)1.3470 (6)0.6633 (3)0.0721 (16)
H9A0.19511.31380.61870.108*
H9B0.03141.40760.65450.108*
H9C0.23561.40640.68840.108*
N10.3986 (4)0.8991 (3)0.59586 (16)0.0273 (7)
N20.6555 (5)1.0592 (3)0.51490 (18)0.0387 (9)
H2C0.75051.10500.49560.046*
H2D0.65690.96220.51950.046*
O10.2320 (4)0.7600 (3)0.51346 (16)0.0525 (8)
O20.4979 (4)1.2773 (3)0.53232 (15)0.0411 (7)
S10.0782 (2)1.18406 (15)0.71639 (7)0.0648 (4)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.032 (2)0.025 (2)0.045 (2)0.0035 (18)0.003 (2)0.0020 (18)
C20.059 (3)0.023 (2)0.056 (3)0.004 (2)0.001 (3)0.0060 (18)
C30.072 (3)0.037 (2)0.064 (3)0.016 (2)0.022 (3)0.006 (2)
C40.057 (3)0.042 (2)0.039 (2)0.001 (2)0.011 (2)0.001 (2)
C50.030 (2)0.027 (2)0.033 (2)0.0019 (18)0.0036 (18)0.0012 (17)
C60.030 (2)0.0220 (19)0.034 (2)0.0003 (16)0.0065 (18)0.0003 (16)
C70.035 (2)0.029 (2)0.042 (2)0.0012 (18)0.001 (2)0.0007 (17)
C80.037 (3)0.041 (2)0.048 (3)0.0056 (19)0.008 (2)0.001 (2)
C90.068 (4)0.070 (3)0.078 (4)0.025 (3)0.002 (3)0.015 (3)
N10.0270 (17)0.0197 (15)0.0352 (17)0.0014 (13)0.0011 (15)0.0003 (13)
N20.0356 (19)0.0180 (15)0.063 (2)0.0001 (14)0.0140 (18)0.0029 (16)
O10.0646 (19)0.0279 (15)0.065 (2)0.0070 (14)0.0292 (17)0.0070 (14)
O20.0367 (14)0.0190 (13)0.0677 (19)0.0032 (12)0.0031 (14)0.0064 (13)
S10.0622 (8)0.0787 (9)0.0534 (7)0.0154 (7)0.0220 (7)0.0016 (7)
Geometric parameters (Å, º) top
C1—O11.231 (5)C5—N21.325 (5)
C1—N11.362 (5)C5—C61.540 (5)
C1—C21.508 (5)C6—N11.462 (4)
C2—C31.519 (6)C6—C71.539 (5)
C3—C41.528 (6)C7—C81.517 (5)
C4—N11.455 (5)C8—S11.810 (4)
C5—O21.233 (4)C9—S11.806 (5)
O1—C1—N1124.4 (3)N1—C6—C7112.3 (3)
O1—C1—C2127.3 (3)N1—C6—C5112.2 (3)
N1—C1—C2108.3 (3)C7—C6—C5111.4 (3)
C1—C2—C3105.0 (3)C8—C7—C6112.9 (3)
C2—C3—C4105.2 (4)C7—C8—S1113.7 (3)
N1—C4—C3104.0 (3)C1—N1—C4113.6 (3)
O2—C5—N2122.5 (4)C1—N1—C6123.2 (3)
O2—C5—C6120.2 (4)C4—N1—C6123.0 (3)
N2—C5—C6117.3 (3)C9—S1—C8101.4 (2)
O1—C1—C2—C3169.9 (4)O1—C1—N1—C4177.6 (4)
N1—C1—C2—C310.4 (4)C2—C1—N1—C42.2 (4)
C1—C2—C3—C418.1 (5)O1—C1—N1—C62.9 (6)
C2—C3—C4—N119.1 (5)C2—C1—N1—C6176.9 (4)
O2—C5—C6—N1159.4 (3)C3—C4—N1—C113.7 (5)
N2—C5—C6—N121.6 (5)C3—C4—N1—C6171.6 (4)
O2—C5—C6—C732.5 (5)C7—C6—N1—C1120.2 (4)
N2—C5—C6—C7148.5 (3)C5—C6—N1—C1113.4 (4)
N1—C6—C7—C864.2 (4)C7—C6—N1—C454.0 (5)
C5—C6—C7—C8168.9 (3)C5—C6—N1—C472.4 (5)
C6—C7—C8—S1176.2 (3)C7—C8—S1—C967.0 (4)

Experimental details

Crystal data
Chemical formulaC9H16N2O2S
Mr216.30
Crystal system, space groupOrthorhombic, P212121
Temperature (K)273
a, b, c (Å)7.018 (6), 8.818 (7), 18.760 (16)
V3)1161.0 (17)
Z4
Radiation typeMo Kα
µ (mm1)0.26
Crystal size (mm)0.30 × 0.25 × 0.20
Data collection
DiffractometerBruker SMART CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Sheldrick, 1996)
Tmin, Tmax0.927, 0.950
No. of measured, independent and
observed [I > 2σ(I)] reflections
4477, 2047, 1574
Rint0.047
(sin θ/λ)max1)0.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.062, 0.120, 1.08
No. of reflections2047
No. of parameters128
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.25, 0.20
Absolute structure(Flack, 1983), 830 Friedel pairs
Absolute structure parameter0.02 (17)

Computer programs: SMART (Bruker, 1997), SMART, SAINT (Bruker, 1997), SHELXS97 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), SHELXTL (Bruker, 1997), SHELXTL.

Selected geometric parameters (Å, º) top
C1—N11.362 (5)C6—N11.462 (4)
C4—N11.455 (5)C8—S11.810 (4)
C5—N21.325 (5)C9—S11.806 (5)
O1—C1—N1124.4 (3)O2—C5—N2122.5 (4)
O1—C1—C2127.3 (3)C9—S1—C8101.4 (2)
N2—C5—C6—C7148.5 (3)C7—C6—N1—C1120.2 (4)
N1—C6—C7—C864.2 (4)C5—C6—N1—C1113.4 (4)
C5—C6—C7—C8168.9 (3)C7—C8—S1—C967.0 (4)
 

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