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Acta Crystallogr Sect E Struct Rep Online. 2012 September 1; 68(Pt 9): o2814.
Published online 2012 August 31. doi:  10.1107/S1600536812036720
PMCID: PMC3435838

N-[(2S)-2-Chloro­propano­yl]glycine

Abstract

The title compound, C5H8ClNO3, was prepared by the nucleophilic substitution reaction of (2S)-2-chloro­propanoyl chloride with glycine. The acetate group forms a dihedral angle of 84.6 (1)° with the mean plane of the C—NH—C=O fragment. In the crystal, the molecules are linked by N—H(...)O and O—H(...)O hydrogen bonds, generating a three-dimensional network, which consolidates the crystal packing.

Related literature  

The title compound is an inter­mediate of Tiopronin [systematic name: N-(2-sulfanyl­propano­yl)glycine], a prescription thiol drug used to control the rate of cystine precipitation and excretion in the disease cystinuria, see: Wang et al. (1993 [triangle]). For a related structure, see: Lv et al. (2007 [triangle]).

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Object name is e-68-o2814-scheme1.jpg

Experimental  

Crystal data  

  • C5H8ClNO3
  • M r = 165.57
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-68-o2814-efi1.jpg
  • a = 5.5170 (11) Å
  • b = 11.622 (2) Å
  • c = 11.964 (2) Å
  • V = 767.1 (3) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.45 mm−1
  • T = 293 K
  • 0.30 × 0.20 × 0.10 mm

Data collection  

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (North et al. , 1968 [triangle]) T min = 0.878, T max = 0.957
  • 1630 measured reflections
  • 1413 independent reflections
  • 1283 reflections with I > 2σ(I)
  • R int = 0.024
  • 3 standard reflections every 200 reflections intensity decay: 1%

Refinement  

  • R[F 2 > 2σ(F 2)] = 0.035
  • wR(F 2) = 0.100
  • S = 1.00
  • 1413 reflections
  • 91 parameters
  • H-atom parameters constrained
  • Δρmax = 0.22 e Å−3
  • Δρmin = −0.21 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 545 Friedel pairs
  • Flack parameter: 0.19 (9)

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 [triangle]); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo,1995 [triangle]); program(s) used to solve structure: SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812036720/cv5331sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812036720/cv5331Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536812036720/cv5331Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

The authors thank the Center of Testing and Analysis, Nanjing University, for support.

supplementary crystallographic information

Comment

The title compound, (I), is an important intermediate in the synthesis of Tiopronin (Wang et al., 1993), which is a prescription thiol drug used to control the rate of cystine precipitation and excretion in the disease cystinuria. Herewith we report the synthesis and the crystal structure of (I).

In the molecule of (I) (Fig. 1), the bond lengths and angles are within normal ranges and correspond to those observed in the related compound (Lv et al., 2007). Atoms C2, C3, O1, N and C4 are nearly coplanar, with a dihedral angle of 0.7 (3)° between the C2/C3/O1 and O1/C3/N/C4 planes, the acetate group forms a dihedral angle of 84.6 (1)° with the mean plane of C4—N1(H1)—C3═O1 fragment. The quiral atom C2 shows an S absolute configuration. Intermolecular N—H···O and O—H···O hydrogen bonds (Table 1) link the molecules into a three-dimensional network, which consolidate the crystal packing.

Experimental

An aqueous solution of 120 g (1.6 mole) of glycine and 84.8 g (0.8 mole) of sodium carbonate is placed in a 1L four-necked flask fitted with a mechanical stirrer and two dropping funnels. The flask is cooled in an ice bath, and 203.2 g (1.6 mol) of (2S)-2-chloropropanoyl chloride and 400 ml of 4 N sodium carbonate are added simultaneously to the vigorously stirred solution over a period of 20–25 minutes. The mixture is stirred for an additional 3 h. The aqueous solution is cooled in an ice bath and acidified to Congo red with concentrated hydrochloric acid.The title compound was extracted from the reaction mixture using ethyl acetate and subsequently crystallized from the same solvent (yield 212 g, 80%; m.p. 377–378 K).

Refinement

H atoms were positioned geometrically, with O—H = 0.85 Å, N— H = 0.86 Å and C—H = 0.96, 0.97 and 0.98 Å for methyl, methylene and methine H, respectively, and constrained to ride on their parent atoms, with Uiso(H) = xUeq(C,N,O), where x = 1.5 for OH and methyl H, and x = 1.2 for all other H atoms.

Figures

Fig. 1.
The molecular structure of (I), showing the atom-numbering scheme and displacement ellipsoids at the 30% probability level.

Crystal data

C5H8ClNO3F(000) = 344
Mr = 165.57Dx = 1.434 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 25 reflections
a = 5.5170 (11) Åθ = 9–13°
b = 11.622 (2) ŵ = 0.45 mm1
c = 11.964 (2) ÅT = 293 K
V = 767.1 (3) Å3Block, colourless
Z = 40.30 × 0.20 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer1283 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.024
Graphite monochromatorθmax = 25.4°, θmin = 2.4°
ω/2θ scansh = 0→6
Absorption correction: ψ scan (North et al. , 1968)k = 0→14
Tmin = 0.878, Tmax = 0.957l = −14→14
1630 measured reflections3 standard reflections every 200 reflections
1413 independent reflections intensity decay: 1%

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.035H-atom parameters constrained
wR(F2) = 0.100w = 1/[σ2(Fo2) + (0.0769P)2] where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
1413 reflectionsΔρmax = 0.22 e Å3
91 parametersΔρmin = −0.21 e Å3
0 restraintsAbsolute structure: Flack (1983), 545 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.19 (9)

Special details

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)

xyzUiso*/Ueq
Cl1.07098 (13)−0.02109 (7)0.44996 (6)0.0614 (3)
N10.6201 (3)0.14605 (16)0.59648 (15)0.0380 (4)
H10.54550.16040.53490.046*
O10.8581 (4)0.02471 (16)0.69152 (14)0.0539 (5)
C10.6872 (4)−0.1485 (2)0.5215 (2)0.0428 (5)
H1A0.5231−0.15060.54810.064*
H1B0.7926−0.18190.57650.064*
H1C0.6990−0.19140.45310.064*
O20.9834 (3)0.30550 (15)0.63454 (14)0.0454 (4)
C20.7635 (4)−0.02114 (18)0.49985 (19)0.0400 (5)
H2A0.65730.01260.44290.048*
O30.7988 (3)0.36913 (16)0.78778 (13)0.0510 (5)
H3A0.91570.41670.78850.077*
C30.7545 (4)0.05143 (17)0.60461 (17)0.0358 (5)
C40.5972 (4)0.22508 (19)0.68892 (17)0.0348 (5)
H4A0.57760.18180.75770.042*
H4B0.45320.27180.67850.042*
C50.8171 (4)0.30310 (18)0.69913 (16)0.0319 (4)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl0.0554 (4)0.0715 (5)0.0574 (4)−0.0122 (3)0.0123 (3)0.0006 (3)
N10.0455 (11)0.0322 (9)0.0364 (9)0.0033 (8)−0.0140 (8)−0.0019 (8)
O10.0702 (12)0.0506 (9)0.0408 (9)0.0207 (8)−0.0128 (8)0.0012 (8)
C10.0344 (11)0.0356 (11)0.0584 (14)−0.0128 (10)0.0106 (11)−0.0106 (11)
O20.0451 (9)0.0525 (10)0.0386 (8)−0.0076 (8)0.0090 (7)−0.0003 (7)
C20.0417 (11)0.0370 (11)0.0412 (12)0.0026 (10)−0.0048 (10)−0.0003 (9)
O30.0569 (10)0.0583 (10)0.0379 (8)−0.0186 (9)0.0058 (8)−0.0159 (8)
C30.0391 (11)0.0322 (10)0.0361 (11)0.0026 (9)−0.0079 (10)0.0003 (8)
C40.0354 (11)0.0333 (10)0.0358 (11)0.0008 (9)0.0013 (9)−0.0033 (9)
C50.0359 (10)0.0357 (10)0.0240 (9)−0.0009 (9)0.0000 (9)0.0036 (8)

Geometric parameters (Å, º)

Cl—C21.798 (2)O2—C51.200 (3)
N1—C31.330 (3)C2—C31.512 (3)
N1—C41.443 (3)C2—H2A0.9800
N1—H10.8600O3—C51.313 (3)
O1—C31.227 (3)O3—H3A0.8500
C1—C21.561 (3)C4—C51.520 (3)
C1—H1A0.9600C4—H4A0.9700
C1—H1B0.9600C4—H4B0.9700
C1—H1C0.9600
C3—N1—C4121.28 (18)Cl—C2—H2A109.5
C3—N1—H1119.4C5—O3—H3A109.3
C4—N1—H1119.4O1—C3—N1122.1 (2)
C2—C1—H1A109.5O1—C3—C2123.12 (18)
C2—C1—H1B109.5N1—C3—C2114.78 (18)
H1A—C1—H1B109.5N1—C4—C5111.79 (18)
C2—C1—H1C109.5N1—C4—H4A109.3
H1A—C1—H1C109.5C5—C4—H4A109.3
H1B—C1—H1C109.5N1—C4—H4B109.3
C3—C2—C1112.52 (19)C5—C4—H4B109.3
C3—C2—Cl107.82 (15)H4A—C4—H4B107.9
C1—C2—Cl108.03 (15)O2—C5—O3124.4 (2)
C3—C2—H2A109.5O2—C5—C4124.94 (19)
C1—C2—H2A109.5O3—C5—C4110.62 (17)
C4—N1—C3—O12.5 (3)Cl—C2—C3—N1115.56 (18)
C4—N1—C3—C2−178.9 (2)C3—N1—C4—C579.1 (3)
C1—C2—C3—O153.1 (3)N1—C4—C5—O24.9 (3)
Cl—C2—C3—O1−65.9 (3)N1—C4—C5—O3−176.05 (18)
C1—C2—C3—N1−125.4 (2)

Hydrogen-bond geometry (Å, º)

D—H···AD—HH···AD···AD—H···A
N1—H1···O2i0.862.092.920 (3)161
O3—H3A···O1ii0.851.792.629 (3)172

Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) −x+2, y+1/2, −z+3/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: CV5331).

References

  • Enraf–Nonius (1994). CAD-4 EXPRESS Enraf–Nonius, Delft, The Netherlands.
  • Flack, H. D. (1983). Acta Cryst. A39, 876–881.
  • Harms, K. & Wocadlo, S. (1995). XCAD4 University of Marburg, Germany.
  • Lv, Z.-F., Gao, X.-S., Wu, W.-Y., Gao, X.-F. & Wang, J.-T. (2007). Acta Cryst. E63, o485–o486.
  • North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Wang, D.-Y., Zhang, C.-Z., Liu, J. & Shi, W.-H. (1993). Zhongguo Yiyao Gongye Zazhi, 24, 243.

Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography