N-[(2S)-2-Chloro­propano­yl]glycine

Sun, H.; Tang, Y.; Li, Y.; Xu, N.; Xu, H.

doi:10.1107/S1600536812036720

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 68| Part 9| September 2012| Page o2814

doi:10.1107/S1600536812036720

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N-[(2S)-2-Chloropropanoyl]glycine

Hong-shun Sun,^a ^* Yi Tang,^b Yu-long Li,^a Ning Xu ^a and Hong Xu ^a

^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 ). For a related structure, see: Lv et al. (2007 ).

Experimental

Crystal data

C₅H₈ClNO₃
M_r = 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 ) 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[F² > 2σ(F²)] = 0.035
wR(F²) = 0.100
S = 1.00
1413 reflections
91 parameters
H-atom parameters constrained
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.21 e Å⁻³
Absolute structure: Flack (1983 ), 545 Friedel pairs
Flack parameter: 0.19 (9)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	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 ); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo,1995 ); program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536812036720/cv5331sup1.cif

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

Supporting information file. DOI: 10.1107/S1600536812036720/cv5331Isup3.cml

checkCIF report

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)—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.

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).

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

C₅H₈ClNO₃	F(000) = 344
M_r = 165.57	D_x = 1.434 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 25 reflections
a = 5.5170 (11) Å	θ = 9–13°
b = 11.622 (2) Å	µ = 0.45 mm⁻¹
c = 11.964 (2) Å	T = 293 K
V = 767.1 (3) Å³	Block, colourless
Z = 4	0.30 × 0.20 × 0.10 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	1283 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.024
Graphite monochromator	θ_max = 25.4°, θ_min = 2.4°
ω/2θ scans	h = 0→6
Absorption correction: ψ scan (North et al. , 1968)	k = 0→14
T_min = 0.878, T_max = 0.957	l = −14→14
1630 measured reflections	3 standard reflections every 200 reflections
1413 independent reflections	intensity decay: 1%

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.035	H-atom parameters constrained
wR(F²) = 0.100	w = 1/[σ²(F_o²) + (0.0769P)²] where P = (F_o² + 2F_c²)/3
S = 1.00	(Δ/σ)_max < 0.001
1413 reflections	Δρ_max = 0.22 e Å⁻³
91 parameters	Δρ_min = −0.21 e Å⁻³
0 restraints	Absolute structure: Flack (1983), 545 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.19 (9)

Crystal data top

C₅H₈ClNO₃	V = 767.1 (3) Å³
M_r = 165.57	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 5.5170 (11) Å	µ = 0.45 mm⁻¹
b = 11.622 (2) Å	T = 293 K
c = 11.964 (2) Å	0.30 × 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)	R_int = 0.024
T_min = 0.878, T_max = 0.957	3 standard reflections every 200 reflections
1630 measured reflections	intensity decay: 1%
1413 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.035	H-atom parameters constrained
wR(F²) = 0.100	Δρ_max = 0.22 e Å⁻³
S = 1.00	Δρ_min = −0.21 e Å⁻³
1413 reflections	Absolute structure: Flack (1983), 545 Friedel pairs
91 parameters	Absolute 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

	x	y	z	U_iso*/U_eq
Cl	1.07098 (13)	−0.02109 (7)	0.44996 (6)	0.0614 (3)
N1	0.6201 (3)	0.14605 (16)	0.59648 (15)	0.0380 (4)
H1	0.5455	0.1604	0.5349	0.046*
O1	0.8581 (4)	0.02471 (16)	0.69152 (14)	0.0539 (5)
C1	0.6872 (4)	−0.1485 (2)	0.5215 (2)	0.0428 (5)
H1A	0.5231	−0.1506	0.5481	0.064*
H1B	0.7926	−0.1819	0.5765	0.064*
H1C	0.6990	−0.1914	0.4531	0.064*
O2	0.9834 (3)	0.30550 (15)	0.63454 (14)	0.0454 (4)
C2	0.7635 (4)	−0.02114 (18)	0.49985 (19)	0.0400 (5)
H2A	0.6573	0.0126	0.4429	0.048*
O3	0.7988 (3)	0.36913 (16)	0.78778 (13)	0.0510 (5)
H3A	0.9157	0.4167	0.7885	0.077*
C3	0.7545 (4)	0.05143 (17)	0.60461 (17)	0.0358 (5)
C4	0.5972 (4)	0.22508 (19)	0.68892 (17)	0.0348 (5)
H4A	0.5776	0.1818	0.7577	0.042*
H4B	0.4532	0.2718	0.6785	0.042*
C5	0.8171 (4)	0.30310 (18)	0.69913 (16)	0.0319 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl	0.0554 (4)	0.0715 (5)	0.0574 (4)	−0.0122 (3)	0.0123 (3)	0.0006 (3)
N1	0.0455 (11)	0.0322 (9)	0.0364 (9)	0.0033 (8)	−0.0140 (8)	−0.0019 (8)
O1	0.0702 (12)	0.0506 (9)	0.0408 (9)	0.0207 (8)	−0.0128 (8)	0.0012 (8)
C1	0.0344 (11)	0.0356 (11)	0.0584 (14)	−0.0128 (10)	0.0106 (11)	−0.0106 (11)
O2	0.0451 (9)	0.0525 (10)	0.0386 (8)	−0.0076 (8)	0.0090 (7)	−0.0003 (7)
C2	0.0417 (11)	0.0370 (11)	0.0412 (12)	0.0026 (10)	−0.0048 (10)	−0.0003 (9)
O3	0.0569 (10)	0.0583 (10)	0.0379 (8)	−0.0186 (9)	0.0058 (8)	−0.0159 (8)
C3	0.0391 (11)	0.0322 (10)	0.0361 (11)	0.0026 (9)	−0.0079 (10)	0.0003 (8)
C4	0.0354 (11)	0.0333 (10)	0.0358 (11)	0.0008 (9)	0.0013 (9)	−0.0033 (9)
C5	0.0359 (10)	0.0357 (10)	0.0240 (9)	−0.0009 (9)	0.0000 (9)	0.0036 (8)

Geometric parameters (Å, º) top

Cl—C2	1.798 (2)	O2—C5	1.200 (3)
N1—C3	1.330 (3)	C2—C3	1.512 (3)
N1—C4	1.443 (3)	C2—H2A	0.9800
N1—H1	0.8600	O3—C5	1.313 (3)
O1—C3	1.227 (3)	O3—H3A	0.8500
C1—C2	1.561 (3)	C4—C5	1.520 (3)
C1—H1A	0.9600	C4—H4A	0.9700
C1—H1B	0.9600	C4—H4B	0.9700
C1—H1C	0.9600

C3—N1—C4	121.28 (18)	Cl—C2—H2A	109.5
C3—N1—H1	119.4	C5—O3—H3A	109.3
C4—N1—H1	119.4	O1—C3—N1	122.1 (2)
C2—C1—H1A	109.5	O1—C3—C2	123.12 (18)
C2—C1—H1B	109.5	N1—C3—C2	114.78 (18)
H1A—C1—H1B	109.5	N1—C4—C5	111.79 (18)
C2—C1—H1C	109.5	N1—C4—H4A	109.3
H1A—C1—H1C	109.5	C5—C4—H4A	109.3
H1B—C1—H1C	109.5	N1—C4—H4B	109.3
C3—C2—C1	112.52 (19)	C5—C4—H4B	109.3
C3—C2—Cl	107.82 (15)	H4A—C4—H4B	107.9
C1—C2—Cl	108.03 (15)	O2—C5—O3	124.4 (2)
C3—C2—H2A	109.5	O2—C5—C4	124.94 (19)
C1—C2—H2A	109.5	O3—C5—C4	110.62 (17)

C4—N1—C3—O1	2.5 (3)	Cl—C2—C3—N1	115.56 (18)
C4—N1—C3—C2	−178.9 (2)	C3—N1—C4—C5	79.1 (3)
C1—C2—C3—O1	53.1 (3)	N1—C4—C5—O2	4.9 (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) top

D—H···A	D—H	H···A	D···A	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−1/2, −y+1/2, −z+1; (ii) −x+2, y+1/2, −z+3/2.

Experimental details

Crystal data
Chemical formula	C₅H₈ClNO₃
M_r	165.57
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	293
a, b, c (Å)	5.5170 (11), 11.622 (2), 11.964 (2)
V (Å³)	767.1 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.45
Crystal size (mm)	0.30 × 0.20 × 0.10

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	ψ scan (North et al. , 1968)
T_min, T_max	0.878, 0.957
No. of measured, independent and observed [I > 2σ(I)] reflections	1630, 1413, 1283
R_int	0.024
(sin θ/λ)_max (Å⁻¹)	0.603

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.035, 0.100, 1.00
No. of reflections	1413
No. of parameters	91
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.22, −0.21
Absolute structure	Flack (1983), 545 Friedel pairs
Absolute structure parameter	0.19 (9)

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

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	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−1/2, −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

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