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Acta Crystallogr Sect E Struct Rep Online. 2010 February 1; 66(Pt 2): o324.
Published online 2010 January 9. doi:  10.1107/S1600536810000176
PMCID: PMC2979941

Valyl benzyl ester chloride

Abstract

In the title compound (systematic name: 1-benz­yloxy-3-methyl-1-oxobutan-2-aminium chloride), C12H18NO2 +·Cl, the ester group is approximately planar, with a maximum deviation of 0.040 (2) Å from the least-squares plane, and makes a dihedral angle of 28.92 (16)° with the phenyl ring. The crystal structure is organized by N—H(...)Cl hydrogen bonds which join the two components into a chain along the b axis. Pairs of chains arranged anti­parallel are inter­connected by further N—H(...)Cl hydrogen bonds, forming eight-membered rings. Similar packing modes have been observed in a number of amino acid ester halides with a short unit-cell parameter of ca 5.5 Å along the direction in which the chains run.

Related literature

For valsartan, see: Black et al. (1997 [triangle]); Buhlmayer et al. (1994 [triangle]). For related structures, see: Bryndal et al. (2006 [triangle]); Jaeger et al. (2003 [triangle]); Nastopoulos et al. (1987 [triangle]). For a description of the Cambridge Structural Database, see: Allen (2002 [triangle]). For graph-set motifs, see: Bernstein et al. (1995 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-0o324-scheme1.jpg

Experimental

Crystal data

  • C12H18NO2 +·Cl
  • M r = 243.72
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o324-efi4.jpg
  • a = 9.705 (1) Å
  • b = 5.406 (1) Å
  • c = 13.116 (2) Å
  • β = 96.58 (1)°
  • V = 683.60 (18) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.27 mm−1
  • T = 295 K
  • 0.4 × 0.2 × 0.2 mm

Data collection

  • Oxford Diffraction Xcalibur Sapphire2 diffractometer
  • Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009 [triangle]) T min = 0.741, T max = 0.948
  • 2649 measured reflections
  • 2010 independent reflections
  • 1652 reflections with I > 2σ(I)
  • R int = 0.023

Refinement

  • R[F 2 > 2σ(F 2)] = 0.034
  • wR(F 2) = 0.077
  • S = 1.06
  • 2010 reflections
  • 159 parameters
  • 1 restraint
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.17 e Å−3
  • Δρmin = −0.24 e Å−3
  • Absolute structure: Flack (1983 [triangle]), 530 Friedel pairs
  • Flack parameter: 0.02 (8)

Data collection: CrysAlis PRO (Oxford Diffraction, 2009 [triangle]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SIR92 (Altomare et al., 1993 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: Stereochemical Workstation Operation Manual (Siemens, 1989 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810000176/is2507sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810000176/is2507Isup2.hkl

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

Acknowledgments

BPS thanks Cipla, Bangalore for the gift of a sample of the title compound

supplementary crystallographic information

Comment

The title compound (I, Scheme 1), valyl benzyl ester chloride [1-(benzyloxy)-3-methyl-1-oxobutan-2-aminium chloride], is a reactant (Buhlmayer et al., 1994) for the synthesis of valsartan, which belongs to the class of angiotensin II receptor antagonists (Black et al., 1997).

The ester fragment C2/C1/O1/O11/C12 (Fig. 1) is in a good approximation planar, maximum deviation from the least squares plane being 0.040 (2) Å, and it makes a dihedral angle of 28.92 (16)° with the plane of the phenyl ring [planar within 0.009 (3) Å]. The C2—C3 bond is almost perpendicular to the plane of ester group, the torsion angle O11—C1—C2—C3 being -82.2 (3)°.

In the crystal structure, the N—H···Cl hydrogen bonds between the cations and chloride anions join the ionic components into the chains along the b direction (Fig. 2 and Table 1). Within these chains there are additional relatively short and linear C—H···O hydrogen bonds involving the C=O oxygen atom. Using graph-set notation (Bernstein et al., 1995), there are two second-order antiparallel C21(4) chains which are interconnected by another hydrogen bonds into two different kinds of third-order hydrogen bonded R42(8) rings. Similar packing was observed in a number of the amino acid ester halides, and it always was connected with the unit-cell parameter of ca 5.5 Å. In the Cambridge Structural Database (Allen, 2002), there are 25 organic structures of the amino acid ester halides, and 10 of them display similar crystal packing and appropriate unit-cell parameter. For instance, L-tyrosyl methyl ester chloride (Bryndal et al., 2006) crystallizes in P212121 space group with one of the unit-cell parameters 5.424 (2) Å, valyl methyl ester chloride (Jaeger et al., 2003) - also P212121, with 5.894 (2) Å, and (S-benzyl-L-cysteine methyl ester hydrochloride (Nastopoulos et al., 1987) - in P21 with c = 5.211 (2) Å.

The coordination of Cl ion by three hydrogen bonded N—H groups might be described as a trigonal pyramid with N—H groups at the base and Cl ion in the apex. The H···Cl···H angles are in the range 77–118°, and the sum of these angles is 277°. It might be noted that if these coordination is described as tetragonal, the empty coordination place is taken by relatively strong C—H(methyl)···Cl hydrogen bond (Table 1).

Experimental

The title compound was obtained as a gift sample from Cipla, Bangalore, India. X-ray quality crystals were obtained from slow evaporation of an aqueous solution (m.p. 409–412 K).

Refinement

Positional and isotropic thermal parameters of the H atoms from the NH3 group were freely refined. All other H atoms were put in the calculated idealized positions (C—H = 0.93–0.97 Å) and refined as riding, with Uiso's set at 1.2 (1.4 for methyl groups) times the Ueq's of appropriate carrier atoms.

Figures

Fig. 1.
Anisotropic ellipsoid representation of the title compound together with atom labelling scheme. The ellipsoids are drawn at 50% probability level, hydrogen atoms are depicted as spheres with arbitrary radii. Hydrogen bond is shown as dashed line.
Fig. 2.
The hydrogen-bonded structure of the title compound. Hydrogen bonds are shown as dashed lines. [Symmetry codes: (i) 1 - x, 1/2 + y, -z; (ii) x, 1 + y, z; (iii) 1 - x, -1/2 + y, -z; (iv) x, -1 + y, z; (v) 1 - x, -3/2 + y, -z.]

Crystal data

C12H18NO2+·ClF(000) = 260
Mr = 243.72Dx = 1.184 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 1449 reflections
a = 9.705 (1) Åθ = 2.1–26.9°
b = 5.406 (1) ŵ = 0.27 mm1
c = 13.116 (2) ÅT = 295 K
β = 96.58 (1)°Prism, colourless
V = 683.60 (18) Å30.4 × 0.2 × 0.2 mm
Z = 2

Data collection

Oxford Diffraction Xcalibur Sapphire2 diffractometer2010 independent reflections
Radiation source: Nova (Mo) X-ray Source1652 reflections with I > 2σ(I)
graphiteRint = 0.023
Detector resolution: 5.2679 pixels mm-1θmax = 26.9°, θmin = 2.1°
ω scanh = −10→12
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2009)k = −4→6
Tmin = 0.741, Tmax = 0.948l = −15→11
2649 measured reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.034H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.077w = 1/[σ2(Fo2) + (0.040P)2] where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max = 0.001
2010 reflectionsΔρmax = 0.17 e Å3
159 parametersΔρmin = −0.24 e Å3
1 restraintAbsolute structure: Flack (1983), 530 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.02 (8)

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
C10.6929 (3)1.0154 (5)0.2145 (2)0.0492 (6)
O110.7115 (2)0.9397 (3)0.31112 (13)0.0744 (6)
C120.6987 (5)1.1297 (7)0.3890 (2)0.0963 (12)
H12A0.61001.21320.37560.116*
H12B0.77191.25160.38780.116*
C130.7099 (4)1.0030 (7)0.4919 (2)0.0766 (10)
C140.6351 (4)1.0998 (9)0.5647 (2)0.1010 (13)
H140.57911.23800.55060.121*
C150.6452 (6)0.9849 (14)0.6612 (3)0.128 (2)
H150.59471.04790.71140.154*
C160.7258 (7)0.7875 (13)0.6824 (4)0.137 (3)
H160.73140.71460.74690.165*
C170.7994 (6)0.6933 (11)0.6098 (4)0.1375 (18)
H170.85440.55390.62430.165*
C180.7931 (5)0.8035 (8)0.5143 (3)0.1053 (14)
H180.84590.74110.46530.126*
O10.6602 (2)1.2196 (4)0.18837 (14)0.0702 (6)
C20.7212 (2)0.8078 (4)0.14310 (17)0.0454 (6)
H20.68510.65360.16910.054*
N20.6429 (2)0.8642 (6)0.04138 (15)0.0476 (5)
H2A0.678 (3)1.021 (7)0.013 (2)0.071 (10)*
H2B0.649 (3)0.740 (6)−0.0041 (19)0.049 (8)*
H2C0.546 (3)0.867 (7)0.0479 (16)0.064 (7)*
C30.8749 (3)0.7732 (5)0.1324 (2)0.0558 (7)
H30.88060.64640.07960.067*
C40.9422 (3)1.0029 (7)0.0953 (3)0.0886 (11)
H4A0.93741.13350.14440.124*
H4B0.89451.05260.03040.124*
H4C1.03750.96880.08760.124*
C50.9560 (3)0.6756 (7)0.2299 (3)0.0844 (10)
H5A1.04810.63210.21630.118*
H5B0.91030.53210.25300.118*
H5C0.96090.80100.28200.118*
Cl10.33538 (6)0.86692 (12)0.08481 (4)0.05096 (19)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0545 (16)0.0364 (15)0.0597 (15)−0.0021 (13)0.0201 (12)0.0033 (13)
O110.1207 (16)0.0510 (14)0.0542 (10)0.0173 (11)0.0221 (10)0.0029 (8)
C120.171 (4)0.060 (2)0.0638 (19)0.016 (3)0.040 (2)−0.0077 (17)
C130.107 (3)0.068 (2)0.0550 (17)−0.004 (2)0.0097 (17)−0.0008 (16)
C140.117 (3)0.125 (4)0.062 (2)−0.008 (3)0.019 (2)−0.018 (2)
C150.146 (5)0.179 (6)0.063 (3)−0.054 (4)0.025 (3)−0.021 (3)
C160.181 (6)0.160 (6)0.064 (3)−0.083 (5)−0.015 (3)0.021 (3)
C170.190 (5)0.123 (4)0.089 (3)0.000 (4)−0.030 (3)0.027 (3)
C180.143 (4)0.094 (4)0.078 (2)0.013 (3)0.011 (2)0.013 (2)
O10.1138 (17)0.0358 (12)0.0648 (12)0.0101 (11)0.0265 (11)0.0051 (9)
C20.0508 (14)0.0325 (16)0.0541 (13)−0.0006 (11)0.0122 (10)0.0044 (10)
N20.0450 (12)0.0398 (12)0.0593 (11)−0.0043 (17)0.0117 (9)−0.0056 (15)
C30.0524 (16)0.0503 (16)0.0659 (16)0.0095 (13)0.0117 (13)−0.0058 (13)
C40.055 (2)0.090 (3)0.123 (3)−0.002 (2)0.0227 (18)0.021 (2)
C50.066 (2)0.082 (3)0.100 (2)0.0181 (19)−0.0083 (17)0.0045 (19)
Cl10.0535 (3)0.0506 (4)0.0506 (3)0.0008 (4)0.0137 (2)0.0006 (3)

Geometric parameters (Å, °)

C1—O11.188 (3)C18—H180.9300
C1—O111.324 (3)C2—N21.489 (3)
C1—C21.507 (3)C2—C31.526 (3)
O11—C121.464 (4)C2—H20.9800
C12—C131.506 (4)N2—H2A1.00 (3)
C12—H12A0.9700N2—H2B0.90 (3)
C12—H12B0.9700N2—H2C0.96 (3)
C13—C181.359 (5)C3—C41.509 (4)
C13—C141.368 (5)C3—C51.518 (4)
C14—C151.403 (6)C3—H30.9800
C14—H140.9300C4—H4A0.9600
C15—C161.334 (7)C4—H4B0.9600
C15—H150.9300C4—H4C0.9600
C16—C171.353 (8)C5—H5A0.9600
C16—H160.9300C5—H5B0.9600
C17—C181.382 (6)C5—H5C0.9600
C17—H170.9300
O1—C1—O11124.5 (3)N2—C2—C3110.25 (19)
O1—C1—C2125.0 (2)C1—C2—C3113.5 (2)
O11—C1—C2110.5 (2)N2—C2—H2108.6
C1—O11—C12115.9 (2)C1—C2—H2108.6
O11—C12—C13107.6 (3)C3—C2—H2108.6
O11—C12—H12A110.2C2—N2—H2A110.6 (17)
C13—C12—H12A110.2C2—N2—H2B112.0 (16)
O11—C12—H12B110.2H2A—N2—H2B109.2 (19)
C13—C12—H12B110.2C2—N2—H2C109.3 (13)
H12A—C12—H12B108.5H2A—N2—H2C113 (3)
C18—C13—C14120.1 (4)H2B—N2—H2C102 (3)
C18—C13—C12122.4 (3)C4—C3—C5110.8 (3)
C14—C13—C12117.5 (4)C4—C3—C2113.1 (2)
C13—C14—C15118.2 (5)C5—C3—C2112.5 (2)
C13—C14—H14120.9C4—C3—H3106.6
C15—C14—H14120.9C5—C3—H3106.6
C16—C15—C14121.4 (5)C2—C3—H3106.6
C16—C15—H15119.3C3—C4—H4A109.5
C14—C15—H15119.3C3—C4—H4B109.5
C15—C16—C17119.9 (5)H4A—C4—H4B109.5
C15—C16—H16120.0C3—C4—H4C109.5
C17—C16—H16120.0H4A—C4—H4C109.5
C16—C17—C18120.2 (6)H4B—C4—H4C109.5
C16—C17—H17119.9C3—C5—H5A109.5
C18—C17—H17119.9C3—C5—H5B109.5
C13—C18—C17120.1 (4)H5A—C5—H5B109.5
C13—C18—H18119.9C3—C5—H5C109.5
C17—C18—H18119.9H5A—C5—H5C109.5
N2—C2—C1107.1 (2)H5B—C5—H5C109.5
O1—C1—O11—C12−4.1 (4)C12—C13—C18—C17−179.8 (4)
C2—C1—O11—C12175.1 (3)C16—C17—C18—C13−1.8 (7)
C1—O11—C12—C13174.8 (3)O1—C1—C2—N2−25.0 (4)
O11—C12—C13—C1834.5 (5)O11—C1—C2—N2155.9 (2)
O11—C12—C13—C14−147.1 (3)O1—C1—C2—C396.9 (3)
C18—C13—C14—C15−1.1 (6)O11—C1—C2—C3−82.2 (3)
C12—C13—C14—C15−179.5 (4)N2—C2—C3—C462.6 (3)
C13—C14—C15—C160.4 (6)C1—C2—C3—C4−57.6 (3)
C14—C15—C16—C17−0.3 (7)N2—C2—C3—C5−170.9 (3)
C15—C16—C17—C181.1 (8)C1—C2—C3—C569.0 (3)
C14—C13—C18—C171.9 (6)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C2—H2···O1i0.982.383.301 (3)157
N2—H2A···Cl1ii1.00 (3)2.26 (4)3.201 (3)156 (2)
N2—H2B···Cl1iii0.90 (3)2.29 (3)3.177 (3)166 (2)
N2—H2C···Cl10.96 (3)2.15 (3)3.101 (2)172.1 (18)
C4—H4C···Cl1iv0.962.953.904 (3)175

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IS2507).

References

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  • Flack, H. D. (1983). Acta Cryst. A39, 876–881.
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  • Nastopoulos, V., Germain, G., Cordopatis, P. & Voliotis, S. (1987). Acta Cryst. C43, 375–376.
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