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Acta Crystallogr Sect E Struct Rep Online. 2009 December 1; 65(Pt 12): o3026.
Published online 2009 November 7. doi:  10.1107/S1600536809046480
PMCID: PMC2971808

l-Serine methyl ester hydro­chloride

Abstract

In the enanti­opure crystal of the title compound, C4H10NO3 +·Cl, inter­molecular O—H(...)Cl and N—H(...)Cl hydrogen bonds link the mol­ecules into layers parallel to (001).

Related literature

Esterification of the carboxyl group of amino acids plays an important role in the synthesis of peptides, especially due to the increased solubility in non-aquous organic solvents, see: Bodanszky (1993 [triangle]). For related structures, see: Bryndal et al. (2006 [triangle]); Görbitz (1989 [triangle]). For the determination of the absolute structure, see: Flack & Bernardinelli (2000 [triangle]); Flack & Shmueli (2007 [triangle]); Hooft et al. (2008 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o3026-scheme1.jpg

Experimental

Crystal data

  • C4H10NO3 +·Cl
  • M r = 155.58
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o3026-efi1.jpg
  • a = 5.22645 (9) Å
  • b = 6.39388 (14) Å
  • c = 11.6420 (4) Å
  • β = 90.090 (1)°
  • V = 389.04 (2) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.44 mm−1
  • T = 150 K
  • 0.38 × 0.33 × 0.15 mm

Data collection

  • Nonius KappaCCD diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2002 [triangle]) T min = 0.78, T max = 0.93
  • 15456 measured reflections
  • 3449 independent reflections
  • 3242 reflections with I > 2σ(I)
  • R int = 0.030

Refinement

  • R[F 2 > 2σ(F 2)] = 0.022
  • wR(F 2) = 0.058
  • S = 1.07
  • 3449 reflections
  • 100 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.25 e Å−3
  • Δρmin = −0.17 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 1599 Friedel pairs
  • Flack parameter: 0.00 (3)

Data collection: COLLECT (Nonius, 1999 [triangle]); cell refinement: PEAKREF (Schreurs, 2005 [triangle]); data reduction: EVAL15 (Xian et al., 2006 [triangle]) and SADABS (Sheldrick, 2002 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: PLATON.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809046480/vm2012sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809046480/vm2012Isup2.hkl

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

Acknowledgments

Financial assistance for this project was provided by the Dutch Organization for Scientific Research, Chemical Sciences (NWO-CW).

supplementary crystallographic information

Comment

Esterification of the carboxyl group of amino acids plays an important role in the synthesis of peptides, especially due to the increased solubility in non-aquous organic solvents (Bodanszky, 1993). The synthesis of methyl esters is straightforward and can be performed by the reaction of HCl gas with a suspension of the amino acid in methanol. In this reaction the hydrochloride of the amino acid methyl ester is obtained, which is the subject of the present study.

A molecular plot of the title compound (I) is shown in Fig. 1. As a consequence of the protection of the carboxyl group, only the amino group is available as protonation site. The O1—C1—C2—N1 and C4—O1—C1—C2 torsion angles of -175.99 (7) and 179.72 (7) ° indicate an extended structure of the backbone. Nevertheless, we do not see a stabilization of this extended structure by an intramolecular hydrogen bond between the ammonium group and O2. Such a stabilization would require a N—H bond in the plane of O2—C1—C2—N1, which is not the case here. Similar extended structures are also found in the methyl ester hydrochlorides of L-cysteine (Görbitz, 1989) and L-tyrosine (Bryndal et al., 2006). Bond lengths and angles in (I) are as expected (Table 1).

With three H-atoms at N1 and one H-atom at O3 the molecule has four hydrogen bond donors. Three oxygen atoms and the chloride anion could act as hydrogen bond acceptors. In fact, only the chloride is used as a hydrogen bond acceptor, here (Table 2). This results in an infinite two-dimensional hydrogen bonding network parallel to the ab plane, as shown in Fig. 2. In the c direction the hydrogen-bonded planes are separated by hydrophobic OCH3 groups. Interestingly, the two-dimensional motif is also reflected in the morphology of the crystal, where (001) has the smallest dimension.

Despite a β-angle of 90.090 (1)° there is no orthorhombic symmetry in this crystal structure. The Rint value for Laue-symmetry mmm is 31% compared to 2% for 2/m. We also did not find indications for pseudo-orthorhombic twinning. The reflections in the diffraction images were not split, and an analysis of the Fo/Fc listing with the TWINROTMAT routine of PLATON (Spek, 2009) did not suggest the presence of twinning.

Because (I) is derived from enantiopure L-serine, the absolute configuration was known in advance. Nevertheless, the presence of chloride provides enough enantiomorph distinguishing power (Friedif = 123, Flack & Shmueli, 2007) to allow a reliable experimental confirmation of the absolute structure. This was done using the Flack parameter (Flack, 1983), which resulted in x = 0.00 (3), and the Hooft parameter (Hooft et al., 2008), which resulted in y = 0.005 (15). As expected, the standard uncertainty of the Hooft parameter is significantly lower than in the Flack parameter, but both parameters confirm the correct absolute structure of (I).

Experimental

0.4 g of L-serine methyl ester hydrochloride (obtained commercially from Aldrich) was dissolved in 10 ml absolute ethanol followed by slow evaporation at room temperature. Single crystals suitable for X-ray diffraction were obtained after a final seeding step by adding a tiny amount of solid starting material.

Refinement

All H atoms were located in difference Fourier maps. H atoms bonded to N and O atoms were refined freely with isotropic displacement parameters. H(C) atoms were refined using a riding model (including free rotation of the methyl substituents), with C—H = 0.95–1.00 Å and with Uiso(H) = 1.2 (1.5 for methyl groups) times Ueq(C).

Friedel pairs were kept separate during the refinement and the Flack parameter was included in the least-squares matrix using TWIN/BASF instructions in SHELXL97. This has been shown to reduce the uncertainty of the Flack parameter compared to the hole-in-one algorithm (Flack & Bernardinelli, 2000).

Figures

Fig. 1.
Molecular structure of (I), with atom labels and 50% probability displacement ellipsoids for non-H atoms.
Fig. 2.
The packing of (I), viewed down the b axis, showing sheets running parallel to (001) with molecules connected by O—H···Cl and N—H···Cl hydrogen bonds (dashed lines). H atoms not involved ...

Crystal data

C4H10NO3+·ClF(000) = 164
Mr = 155.58Dx = 1.328 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 14244 reflections
a = 5.22645 (9) Åθ = 1.8–35.0°
b = 6.39388 (14) ŵ = 0.44 mm1
c = 11.6420 (4) ÅT = 150 K
β = 90.090 (1)°Irregular plate, colourless
V = 389.04 (2) Å30.38 × 0.33 × 0.15 mm
Z = 2

Data collection

Nonius KappaCCD diffractometer3449 independent reflections
Radiation source: rotating anode3242 reflections with I > 2σ(I)
graphiteRint = 0.030
[var phi] and ω scansθmax = 35.0°, θmin = 1.8°
Absorption correction: multi-scan (SADABS; Sheldrick, 2002)h = −8→8
Tmin = 0.78, Tmax = 0.93k = −10→10
15456 measured reflectionsl = −18→18

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.022H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.058w = 1/[σ2(Fo2) + (0.0329P)2 + 0.0147P] where P = (Fo2 + 2Fc2)/3
S = 1.07(Δ/σ)max = 0.002
3449 reflectionsΔρmax = 0.25 e Å3
100 parametersΔρmin = −0.17 e Å3
1 restraintAbsolute structure: Flack (1983), 1600 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.00 (3)

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
O10.19488 (14)0.39944 (12)0.93010 (6)0.03194 (14)
O20.32242 (18)0.69384 (13)0.84254 (7)0.04120 (18)
O30.57878 (12)0.22667 (10)0.72179 (7)0.02923 (13)
H30.644 (3)0.119 (3)0.6913 (14)0.045 (4)*
N10.25944 (14)0.54258 (11)0.63222 (7)0.02279 (12)
H1A0.411 (3)0.597 (3)0.6391 (12)0.037 (4)*
H1B0.254 (3)0.473 (3)0.5725 (15)0.045 (4)*
H1C0.149 (2)0.643 (2)0.6261 (11)0.029 (3)*
C10.24364 (16)0.51767 (14)0.83958 (7)0.02379 (14)
C20.18095 (14)0.40362 (12)0.72813 (7)0.02175 (13)
H2−0.00840.38270.72390.026*
C30.31005 (16)0.19224 (13)0.71800 (8)0.02470 (14)
H3A0.25710.10030.78210.030*
H3B0.26160.12420.64470.030*
C40.2501 (2)0.49492 (19)1.04131 (9)0.0378 (2)
H4A0.43220.53071.04560.057*
H4B0.20790.39611.10280.057*
H4C0.14730.62201.05020.057*
Cl10.77391 (3)0.81723 (3)0.608559 (15)0.02488 (4)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0416 (3)0.0290 (3)0.0252 (3)−0.0042 (3)0.0023 (2)0.0007 (2)
O20.0668 (5)0.0250 (3)0.0317 (3)−0.0129 (4)−0.0020 (3)−0.0044 (3)
O30.0229 (3)0.0219 (3)0.0429 (4)0.0033 (2)−0.0034 (2)−0.0061 (2)
N10.0220 (3)0.0201 (3)0.0263 (3)0.0021 (2)−0.0026 (2)−0.0013 (2)
C10.0236 (3)0.0218 (3)0.0260 (3)0.0014 (3)0.0001 (3)−0.0023 (3)
C20.0187 (3)0.0196 (3)0.0270 (3)−0.0016 (3)−0.0014 (2)−0.0012 (3)
C30.0250 (3)0.0168 (3)0.0323 (4)−0.0016 (3)−0.0027 (3)−0.0025 (3)
C40.0485 (6)0.0403 (5)0.0248 (4)0.0096 (4)0.0003 (4)−0.0030 (4)
Cl10.02321 (7)0.02180 (7)0.02965 (8)0.00378 (7)0.00166 (5)0.00182 (8)

Geometric parameters (Å, °)

O1—C11.3221 (11)C1—C21.5235 (12)
O1—C41.4598 (13)C2—C31.5153 (12)
O2—C11.1998 (11)C2—H21.0000
O3—C31.4223 (10)C3—H3A0.9900
O3—H30.847 (18)C3—H3B0.9900
N1—C21.4852 (11)C4—H4A0.9800
N1—H1A0.867 (16)C4—H4B0.9800
N1—H1B0.825 (18)C4—H4C0.9800
N1—H1C0.865 (14)
C1—O1—C4115.45 (8)C3—C2—H2108.5
C3—O3—H3104.9 (11)C1—C2—H2108.5
C2—N1—H1A115.1 (10)O3—C3—C2107.42 (6)
C2—N1—H1B107.6 (12)O3—C3—H3A110.2
H1A—N1—H1B108.9 (14)C2—C3—H3A110.2
C2—N1—H1C108.6 (9)O3—C3—H3B110.2
H1A—N1—H1C108.6 (14)C2—C3—H3B110.2
H1B—N1—H1C107.7 (14)H3A—C3—H3B108.5
O2—C1—O1125.48 (9)O1—C4—H4A109.5
O2—C1—C2123.17 (8)O1—C4—H4B109.5
O1—C1—C2111.33 (7)H4A—C4—H4B109.5
N1—C2—C3110.58 (7)O1—C4—H4C109.5
N1—C2—C1107.14 (6)H4A—C4—H4C109.5
C3—C2—C1113.45 (7)H4B—C4—H4C109.5
N1—C2—H2108.5
C4—O1—C1—O2−1.64 (14)O2—C1—C2—C3127.65 (10)
C4—O1—C1—C2179.72 (7)O1—C1—C2—C3−53.67 (9)
O2—C1—C2—N15.33 (11)N1—C2—C3—O359.87 (9)
O1—C1—C2—N1−175.99 (7)C1—C2—C3—O3−60.53 (9)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1A···Cl10.867 (16)2.390 (16)3.2237 (8)161.2 (14)
N1—H1B···Cl1i0.825 (18)2.336 (18)3.1563 (8)172.7 (16)
N1—H1C···Cl1ii0.865 (14)2.264 (14)3.0979 (7)161.9 (12)
O3—H3···Cl1iii0.847 (18)2.261 (18)3.1041 (7)173.9 (15)

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: VM2012).

References

  • Bodanszky, M. (1993). Principles of Peptide Synthesis, 2nd ed., pp. 74–86. Berlin: Springer-Verlag.
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  • Flack, H. D. & Shmueli, U. (2007). Acta Cryst. A63, 257–265. [PubMed]
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