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ISSN: 2056-9890

N-[(2S)-2-Chloro­propano­yl]glycine

aChemical Engineering Department, Nanjing College of Chemical Technology, Geguan Road No. 265 Nanjing, Nanjing 210048, People's Republic of China, and bAnhui University of Architecture, Ziyun Road No. 292, Economic Development Zone, Hefei City, Hefei 210048, People's Republic of China
*Correspondence e-mail: njutshs@126.com

(Received 18 August 2012; accepted 24 August 2012; online 31 August 2012)

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[Wang, D.-Y., Zhang, C.-Z., Liu, J. & Shi, W.-H. (1993). Zhongguo Yiyao Gongye Zazhi, 24, 243.]). For a related structure, see: Lv et al. (2007[Lv, Z.-F., Gao, X.-S., Wu, W.-Y., Gao, X.-F. & Wang, J.-T. (2007). Acta Cryst. E63, o485-o486.]).

[Scheme 1]

Experimental

Crystal data
  • C5H8ClNO3

  • Mr = 165.57

  • Orthorhombic, P 21 21 21

  • 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[North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351-359.]) Tmin = 0.878, Tmax = 0.957

  • 1630 measured reflections

  • 1413 independent reflections

  • 1283 reflections with I > 2σ(I)

  • Rint = 0.024

  • 3 standard reflections every 200 reflections intensity decay: 1%

Refinement
  • R[F2 > 2σ(F2)] = 0.035

  • wR(F2) = 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[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 545 Friedel pairs

  • Flack parameter: 0.19 (9)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1⋯O2i 0.86 2.09 2.920 (3) 161
O3—H3A⋯O1ii 0.85 1.79 2.629 (3) 172
Symmetry codes: (i) [x-{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]; (ii) [-x+2, y+{\script{1\over 2}}, -z+{\script{3\over 2}}].

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994[Enraf-Nonius (1994). CAD-4 EXPRESS. Enraf-Nonius, Delft, The Netherlands.]); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo,1995[Harms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.]); program(s) used to solve structure: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

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)—C3O1 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.

Related literature top

The title compound is an important 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). For a related structure, see: Lv et al. (2007).

Experimental top

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 top

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.

Computing details top

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

Figures top
Figure 1. The molecular structure of (I), showing the atom-numbering scheme and displacement ellipsoids at the 30% probability level.
N-[(2S)-2-Chloropropanoyl]glycine top
Crystal data top
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 top
Enraf–Nonius CAD-4
diffractometer
1283 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.024
Graphite monochromatorθmax = 25.4°, θmin = 2.4°
ω/2θ scansh = 06
Absorption correction: ψ scan
(North et al. , 1968)
k = 014
Tmin = 0.878, Tmax = 0.957l = 1414
1630 measured reflections3 standard reflections every 200 reflections
1413 independent reflections intensity decay: 1%
Refinement top
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) = 0.100 w = 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 methodsAbsolute structure parameter: 0.19 (9)
Crystal data top
C5H8ClNO3V = 767.1 (3) Å3
Mr = 165.57Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 5.5170 (11) ŵ = 0.45 mm1
b = 11.622 (2) ÅT = 293 K
c = 11.964 (2) Å0.30 × 0.20 × 0.10 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer
1283 reflections with I > 2σ(I)
Absorption correction: ψ scan
(North et al. , 1968)
Rint = 0.024
Tmin = 0.878, Tmax = 0.9573 standard reflections every 200 reflections
1630 measured reflections intensity decay: 1%
1413 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.035H-atom parameters constrained
wR(F2) = 0.100Δρmax = 0.22 e Å3
S = 1.00Δρmin = 0.21 e Å3
1413 reflectionsAbsolute structure: Flack (1983), 545 Friedel pairs
91 parametersAbsolute structure parameter: 0.19 (9)
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
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)
H1A0.52310.15060.54810.064*
H1B0.79260.18190.57650.064*
H1C0.69900.19140.45310.064*
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) top
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) top
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—C2178.9 (2)C3—N1—C4—C579.1 (3)
C1—C2—C3—O153.1 (3)N1—C4—C5—O24.9 (3)
Cl—C2—C3—O165.9 (3)N1—C4—C5—O3176.05 (18)
C1—C2—C3—N1125.4 (2)
Hydrogen-bond geometry (Å, º) top
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) x1/2, y+1/2, z+1; (ii) x+2, y+1/2, z+3/2.

Experimental details

Crystal data
Chemical formulaC5H8ClNO3
Mr165.57
Crystal system, space groupOrthorhombic, P212121
Temperature (K)293
a, b, c (Å)5.5170 (11), 11.622 (2), 11.964 (2)
V3)767.1 (3)
Z4
Radiation typeMo Kα
µ (mm1)0.45
Crystal size (mm)0.30 × 0.20 × 0.10
Data collection
DiffractometerEnraf–Nonius CAD-4
diffractometer
Absorption correctionψ scan
(North et al. , 1968)
Tmin, Tmax0.878, 0.957
No. of measured, independent and
observed [I > 2σ(I)] reflections
1630, 1413, 1283
Rint0.024
(sin θ/λ)max1)0.603
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.035, 0.100, 1.00
No. of reflections1413
No. of parameters91
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.22, 0.21
Absolute structureFlack (1983), 545 Friedel pairs
Absolute structure parameter0.19 (9)

Computer programs: CAD-4 EXPRESS (Enraf–Nonius, 1994), XCAD4 (Harms & Wocadlo,1995), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
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) x1/2, y+1/2, z+1; (ii) x+2, y+1/2, z+3/2.
 

Acknowledgements

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

References

First citationEnraf–Nonius (1994). CAD-4 EXPRESS. Enraf–Nonius, Delft, The Netherlands.
First citationFlack, H. D. (1983). Acta Cryst. A39, 876–881.  CrossRef CAS Web of Science IUCr Journals
First citationHarms, K. & Wocadlo, S. (1995). XCAD4. University of Marburg, Germany.
First citationLv, Z.-F., Gao, X.-S., Wu, W.-Y., Gao, X.-F. & Wang, J.-T. (2007). Acta Cryst. E63, o485–o486.  CrossRef IUCr Journals
First citationNorth, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.  CrossRef IUCr Journals Web of Science
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationWang, D.-Y., Zhang, C.-Z., Liu, J. & Shi, W.-H. (1993). Zhongguo Yiyao Gongye Zazhi, 24, 243.

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ISSN: 2056-9890
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