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Acta Crystallogr Sect E Struct Rep Online. 2009 April 1; 65(Pt 4): o743.
Published online 2009 March 14. doi:  10.1107/S1600536809008198
PMCID: PMC2968871

(1′S,2R,3R)-(−)-2-Hydr­oxy-3-morpholino-3-phenyl-N-(1′-phenyl­ethyl)propion­amide

Abstract

In the title compound, C21H26N2O3, the morpholine ring has a chair conformation and the dihedral angle between the two phenyl rings is 59.0 (3)°. The crystal packing is stabilized by inter­molecular O—H(...)O hydrogen bonds, generating a ribbon structure along the a axis. An intra­molecular N—H(...)O contact is also present.

Related literature

For general background, see: Barbaro et al. (1992 [triangle]); Szymanski et al. (2006 [triangle]); Sheppard et al. (2004 [triangle]); Chen et al. (1996 [triangle]); Concellón et al. (2003a [triangle],b [triangle]); Martín et al. (2004 [triangle]). For related structures, see: Romero et al. (2005a [triangle],b [triangle]). For ring conformation analysis, see: Cremer & Pople (1975 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-0o743-scheme1.jpg

Experimental

Crystal data

  • C21H26N2O3
  • M r = 354.44
  • Orthorhombic, An external file that holds a picture, illustration, etc.
Object name is e-65-0o743-efi1.jpg
  • a = 6.0010 (17) Å
  • b = 15.659 (3) Å
  • c = 20.746 (4) Å
  • V = 1949.5 (8) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.08 mm−1
  • T = 293 K
  • 0.72 × 0.28 × 0.16 mm

Data collection

  • Bruker P4 diffractometer
  • Absorption correction: none
  • 3964 measured reflections
  • 2959 independent reflections
  • 1116 reflections with I > 2σ(I)
  • R int = 0.055
  • 3 standard reflections every 97 reflections intensity decay: 3%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.054
  • wR(F 2) = 0.163
  • S = 0.89
  • 2959 reflections
  • 251 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.24 e Å−3
  • Δρmin = −0.19 e Å−3

Data collection: XSCANS (Siemens, 1994 [triangle]); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SIR2004 (Burla et al., 2005 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809008198/is2398sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809008198/is2398Isup2.hkl

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

Acknowledgments

We acknowledge financial support under scholarship DMAS No. 169011 and CONACyT project No. 83185. Special thanks go to Dr Marcos Flores (USAI-FQ-UNAM) for useful comments.

supplementary crystallographic information

Comment

The stereoselective synthesis of α-hydroxyamides (Barbaro et al., 1992; Szymanski et al., 2006) is an important area in asymmetric synthesis because these kinds of intermediates exhibit a great value as synthetic building block in the synthesis of pharmaceutical, agriculture and medicinal compounds (Sheppard et al., 2004; Chen et al., 1996). Numerous methods have been development through the last 10 years. One of the most relevant methodologies is the opening reaction of epoxyamides (Concellón et al., 2003a,b; Martín et al., 2004). In this way, we show herein the regiospecific ring opening reaction of epoxyamide derived from (S)-(-)-phenyl ethyl amine (Scheme 1). Related structures including (S)-(-)-phenyl ethyl amine with different substituents has been previously reported (Romero et al., 2005a,b).

In the present paper, we report the structure of title compound, (I), which shows a single asymmetric unit with two aromatic rings. The morpholine ring shows an almost perfect chair conformation with a puckering parameters (Cremer & Pople, 1975) (O3—C2—C1—N2—C4—C3) Q = 0.572 (4) Å, θ2 = 3.6° (4), [var phi]2 =343° (10), q2 = 0.026 (4) Å and q3 = 0.571 (4) Å. In the crystal structure, the molecules are linked by O—H···O hydrogen bonds (Table 1), generating a ribbon structure along the a axis.

Experimental

The compound (I) was obtained by trans-diastereoisomeric mixture of epoxyamide in anhydrous EtOH. Then, 1.1 equivalents of morpholine were added. The reaction was stirred over night. Finally, the resultant amino alcohol mixture was separate by column chromatography (AcOEt: Petroleum Ether). The absolute configuration of (1'S, 2R, 3R)-(-)-2-hydroxy-3-morpholin-4-yl-3 -phenyl-N-(1'-phenyl-ethyl)-propionamide was established by the structure determination of a (S)-(-)-phenyl ethyl amine of known absolute configuration of starting material [C8 in compound (I)]. The H1 NMR experiment shows only one disteromeric compound.

Refinement

H atoms bonded to N and O atoms and all optically relevant were located in a difference map and refined as riding on their parent atoms with Uiso(H) = 1.2Ueq for N and C—H and Uiso(H) = 1.5Ueq for O atoms. H atoms linked to C atoms were placed in geometrical idealized positions and refined as riding on their parent atoms, with C—H = 0.93–0.98 Å and with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C). In the absence of significant anomalous scattering effects, Friedel pairs were merged and the absolute configuration was assigned on the base of synthetic procedure.

Figures

Fig. 1.
The molecular structure of the title compound, with atom labels and 50% probability displacement ellipsoids for non-H atoms.
Fig. 2.
The packing of the title compound, showing molecules connected by O—H···O hydrogen bonds (dashed lines).

Crystal data

C21H26N2O3Dx = 1.208 Mg m3
Mr = 354.44Melting point: 431 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 30 reflections
a = 6.0010 (17) Åθ = 3.9–23.9°
b = 15.659 (3) ŵ = 0.08 mm1
c = 20.746 (4) ÅT = 293 K
V = 1949.5 (8) Å3Prism, colorless
Z = 40.72 × 0.28 × 0.16 mm
F(000) = 760

Data collection

Bruker P4 diffractometerRint = 0.055
Radiation source: fine-focus sealed tubeθmax = 29.0°, θmin = 1.6°
graphiteh = −1→8
2θ/ω scansk = −1→21
3964 measured reflectionsl = −1→28
2959 independent reflections3 standard reflections every 97 reflections
1116 reflections with I > 2σ(I) intensity decay: 3%

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.054H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.163w = 1/[σ2(Fo2) + (0.0711P)2] where P = (Fo2 + 2Fc2)/3
S = 0.89(Δ/σ)max < 0.001
2959 reflectionsΔρmax = 0.24 e Å3
251 parametersΔρmin = −0.19 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008)
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.008 (2)

Special details

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'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 > 2σ(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
O1−0.1563 (5)0.92034 (19)0.75127 (13)0.0567 (8)
N2−0.1559 (5)0.90373 (19)0.60796 (14)0.0464 (8)
O20.4127 (5)0.96834 (18)0.72379 (13)0.0598 (8)
N10.2201 (6)0.9177 (2)0.81024 (16)0.0516 (9)
C100.0914 (6)0.8018 (2)0.66365 (17)0.0447 (9)
C70.2354 (6)0.9439 (2)0.74924 (19)0.0445 (9)
O3−0.3564 (6)0.9556 (2)0.48787 (14)0.0770 (10)
C50.0430 (7)0.8947 (2)0.64872 (18)0.0449 (9)
C60.0197 (6)0.9474 (2)0.71116 (18)0.0434 (9)
C4−0.2007 (7)0.9933 (2)0.5920 (2)0.0554 (11)
H4A−0.06971.01830.57210.066*
H4B−0.23221.02480.63120.066*
C80.3993 (7)0.9216 (3)0.8565 (2)0.0552 (11)
C150.3024 (8)0.7691 (2)0.65361 (19)0.0535 (10)
H150.41450.80450.63800.064*
C160.5180 (7)0.8364 (3)0.86521 (19)0.0558 (11)
C11−0.0702 (7)0.7484 (3)0.6885 (2)0.0610 (11)
H11−0.21250.76950.69640.073*
C170.4526 (9)0.7626 (3)0.8349 (2)0.0703 (13)
H170.32920.76350.80780.084*
C3−0.3969 (8)1.0009 (3)0.5463 (2)0.0676 (13)
H3A−0.52940.97820.56690.081*
H3B−0.42351.06070.53670.081*
C1−0.1284 (8)0.8570 (3)0.54712 (19)0.0637 (12)
H1A−0.10970.79670.55640.076*
H1B0.00550.87680.52570.076*
C2−0.3229 (9)0.8683 (3)0.5030 (2)0.0765 (15)
H2A−0.29730.83650.46350.092*
H2B−0.45590.84570.52330.092*
C130.1855 (9)0.6310 (3)0.6898 (2)0.0699 (14)
H130.21580.57360.69730.084*
C140.3492 (8)0.6836 (3)0.6666 (2)0.0638 (12)
H140.49180.66230.65940.077*
C210.7048 (9)0.8339 (4)0.9047 (3)0.0896 (17)
H210.75330.88350.92500.107*
C90.3070 (9)0.9542 (4)0.9206 (2)0.0938 (18)
H9A0.23311.00780.91380.141*
H9B0.42710.96180.95060.141*
H9C0.20270.91350.93750.141*
C12−0.0219 (9)0.6627 (3)0.7018 (3)0.0742 (14)
H12−0.13160.62740.71890.089*
C180.5674 (12)0.6867 (3)0.8440 (3)0.0958 (18)
H180.52070.63700.82360.115*
C190.7512 (13)0.6857 (5)0.8837 (4)0.119 (2)
H190.82970.63510.88990.143*
C200.8184 (12)0.7586 (5)0.9141 (3)0.122 (2)
H200.94180.75740.94120.147*
H1O−0.307 (14)0.929 (5)0.735 (4)0.184*
H1N0.059 (12)0.906 (4)0.819 (3)0.147*
H50.180 (12)0.915 (4)0.627 (3)0.147*
H6−0.004 (11)1.009 (4)0.697 (3)0.147*
H80.535 (12)0.960 (4)0.839 (3)0.147*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
O10.0370 (14)0.0800 (19)0.0531 (15)0.0034 (16)0.0045 (14)0.0008 (15)
N20.0476 (19)0.0465 (17)0.0450 (16)0.0034 (17)−0.0023 (16)0.0024 (14)
O20.0429 (17)0.0697 (18)0.0668 (18)−0.0070 (15)0.0011 (15)0.0061 (15)
N10.0388 (18)0.065 (2)0.0507 (19)0.0006 (18)−0.0067 (17)−0.0002 (17)
C100.041 (2)0.045 (2)0.049 (2)0.003 (2)0.0017 (19)0.0029 (17)
C70.038 (2)0.044 (2)0.051 (2)0.0032 (18)−0.001 (2)−0.0001 (19)
O30.091 (3)0.086 (2)0.0543 (17)0.013 (2)−0.0085 (19)0.0103 (16)
C50.041 (2)0.046 (2)0.048 (2)0.0057 (19)0.0005 (19)0.0005 (17)
C60.034 (2)0.047 (2)0.049 (2)0.0020 (19)0.0026 (18)0.0012 (18)
C40.058 (3)0.050 (2)0.058 (2)0.007 (2)−0.009 (2)0.008 (2)
C80.047 (2)0.064 (3)0.055 (2)0.008 (2)−0.011 (2)−0.009 (2)
C150.050 (2)0.052 (2)0.058 (2)0.002 (2)0.005 (2)−0.001 (2)
C160.048 (3)0.067 (3)0.053 (2)0.005 (2)0.002 (2)0.003 (2)
C110.048 (3)0.050 (2)0.085 (3)0.002 (2)0.008 (3)0.009 (2)
C170.069 (3)0.068 (3)0.074 (3)0.007 (3)0.004 (3)0.008 (3)
C30.073 (3)0.072 (3)0.058 (2)0.016 (3)−0.003 (3)0.005 (2)
C10.080 (3)0.061 (2)0.051 (2)0.007 (3)−0.003 (3)−0.010 (2)
C20.083 (4)0.088 (3)0.058 (3)0.004 (3)−0.016 (3)−0.010 (3)
C130.072 (3)0.047 (2)0.090 (3)0.006 (3)−0.002 (3)0.008 (2)
C140.057 (3)0.051 (2)0.084 (3)0.016 (2)0.004 (3)−0.004 (2)
C210.075 (4)0.098 (4)0.096 (4)0.018 (4)−0.030 (3)0.003 (3)
C90.080 (3)0.134 (5)0.068 (3)0.034 (4)−0.018 (3)−0.042 (3)
C120.063 (3)0.052 (3)0.107 (4)−0.003 (2)0.003 (3)0.018 (3)
C180.108 (5)0.063 (3)0.116 (4)0.014 (4)0.016 (4)0.011 (3)
C190.114 (6)0.094 (5)0.149 (6)0.045 (5)−0.001 (5)0.025 (5)
C200.104 (5)0.125 (5)0.137 (6)0.035 (5)−0.042 (5)0.025 (5)

Geometric parameters (Å, °)

O1—C61.410 (5)C16—C211.389 (6)
O1—H1O0.98 (8)C11—C121.401 (6)
N2—C41.466 (5)C11—H110.9300
N2—C11.468 (5)C17—C181.387 (7)
N2—C51.470 (5)C17—H170.9300
O2—C71.248 (4)C3—H3A0.9700
N1—C71.333 (5)C3—H3B0.9700
N1—C81.443 (5)C1—C21.494 (7)
N1—H1N1.00 (7)C1—H1A0.9700
C10—C111.380 (5)C1—H1B0.9700
C10—C151.382 (6)C2—H2A0.9700
C10—C51.514 (5)C2—H2B0.9700
C7—C61.517 (5)C13—C121.363 (7)
O3—C21.416 (5)C13—C141.370 (6)
O3—C31.426 (5)C13—H130.9300
C5—C61.542 (5)C14—H140.9300
C5—H50.99 (7)C21—C201.376 (8)
C6—H61.02 (6)C21—H210.9300
C4—C31.516 (6)C9—H9A0.9600
C4—H4A0.9700C9—H9B0.9600
C4—H4B0.9700C9—H9C0.9600
C8—C161.523 (6)C12—H120.9300
C8—C91.528 (6)C18—C191.376 (9)
C8—H81.08 (7)C18—H180.9300
C15—C141.393 (5)C19—C201.365 (9)
C15—H150.9300C19—H190.9300
C16—C171.373 (6)C20—H200.9300
C6—O1—H1O116 (4)C16—C17—H17119.5
C4—N2—C1107.6 (3)C18—C17—H17119.5
C4—N2—C5111.8 (3)O3—C3—C4111.1 (4)
C1—N2—C5110.8 (3)O3—C3—H3A109.4
C7—N1—C8124.5 (4)C4—C3—H3A109.4
C7—N1—H1N107 (4)O3—C3—H3B109.4
C8—N1—H1N127 (4)C4—C3—H3B109.4
C11—C10—C15118.4 (4)H3A—C3—H3B108.0
C11—C10—C5121.5 (4)N2—C1—C2112.3 (4)
C15—C10—C5120.1 (4)N2—C1—H1A109.1
O2—C7—N1123.7 (4)C2—C1—H1A109.1
O2—C7—C6119.7 (3)N2—C1—H1B109.1
N1—C7—C6116.5 (3)C2—C1—H1B109.1
C2—O3—C3108.5 (3)H1A—C1—H1B107.9
N2—C5—C10111.5 (3)O3—C2—C1111.2 (4)
N2—C5—C6111.0 (3)O3—C2—H2A109.4
C10—C5—C6111.1 (3)C1—C2—H2A109.4
N2—C5—H5112 (4)O3—C2—H2B109.4
C10—C5—H5104 (4)C1—C2—H2B109.4
C6—C5—H5107 (4)H2A—C2—H2B108.0
O1—C6—C7108.7 (3)C12—C13—C14120.0 (4)
O1—C6—C5113.8 (3)C12—C13—H13120.0
C7—C6—C5109.9 (3)C14—C13—H13120.0
O1—C6—H6110 (4)C13—C14—C15120.1 (4)
C7—C6—H6108 (4)C13—C14—H14120.0
C5—C6—H6106 (4)C15—C14—H14120.0
N2—C4—C3111.0 (3)C20—C21—C16120.5 (6)
N2—C4—H4A109.4C20—C21—H21119.8
C3—C4—H4A109.4C16—C21—H21119.8
N2—C4—H4B109.4C8—C9—H9A109.5
C3—C4—H4B109.4C8—C9—H9B109.5
H4A—C4—H4B108.0H9A—C9—H9B109.5
N1—C8—C16113.0 (3)C8—C9—H9C109.5
N1—C8—C9108.8 (3)H9A—C9—H9C109.5
C16—C8—C9111.1 (4)H9B—C9—H9C109.5
N1—C8—H8112 (3)C13—C12—C11120.1 (5)
C16—C8—H8100 (3)C13—C12—H12119.9
C9—C8—H8112 (3)C11—C12—H12119.9
C10—C15—C14120.8 (4)C19—C18—C17119.4 (6)
C10—C15—H15119.6C19—C18—H18120.3
C14—C15—H15119.6C17—C18—H18120.3
C17—C16—C21118.5 (5)C20—C19—C18120.2 (6)
C17—C16—C8123.3 (4)C20—C19—H19119.9
C21—C16—C8118.1 (4)C18—C19—H19119.9
C10—C11—C12120.6 (4)C19—C20—C21120.4 (6)
C10—C11—H11119.7C19—C20—H20119.8
C12—C11—H11119.7C21—C20—H20119.8
C16—C17—C18121.1 (5)
C8—N1—C7—O26.1 (6)N1—C8—C16—C17−3.5 (6)
C8—N1—C7—C6−170.8 (3)C9—C8—C16—C17119.1 (5)
C4—N2—C5—C10−178.6 (3)N1—C8—C16—C21175.0 (4)
C1—N2—C5—C10−58.5 (4)C9—C8—C16—C21−62.5 (5)
C4—N2—C5—C657.0 (4)C15—C10—C11—C12−1.3 (6)
C1—N2—C5—C6177.1 (3)C5—C10—C11—C12179.9 (4)
C11—C10—C5—N2−51.9 (5)C21—C16—C17—C181.0 (7)
C15—C10—C5—N2129.3 (4)C8—C16—C17—C18179.5 (4)
C11—C10—C5—C672.4 (5)C2—O3—C3—C460.3 (5)
C15—C10—C5—C6−106.4 (4)N2—C4—C3—O3−59.3 (5)
O2—C7—C6—O1−177.3 (3)C4—N2—C1—C2−54.6 (5)
N1—C7—C6—O1−0.2 (4)C5—N2—C1—C2−177.1 (4)
O2—C7—C6—C557.6 (5)C3—O3—C2—C1−59.9 (5)
N1—C7—C6—C5−125.4 (3)N2—C1—C2—O359.0 (5)
N2—C5—C6—O163.3 (4)C12—C13—C14—C15−1.7 (7)
C10—C5—C6—O1−61.3 (4)C10—C15—C14—C13−0.3 (7)
N2—C5—C6—C7−174.5 (3)C17—C16—C21—C20−1.3 (8)
C10—C5—C6—C760.9 (4)C8—C16—C21—C20−179.8 (6)
C1—N2—C4—C354.3 (5)C14—C13—C12—C112.1 (8)
C5—N2—C4—C3176.2 (3)C10—C11—C12—C13−0.6 (7)
C7—N1—C8—C16−99.7 (5)C16—C17—C18—C19−0.6 (8)
C7—N1—C8—C9136.4 (4)C17—C18—C19—C200.4 (10)
C11—C10—C15—C141.7 (6)C18—C19—C20—C21−0.7 (11)
C5—C10—C15—C14−179.4 (4)C16—C21—C20—C191.1 (10)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1N···O11.00 (7)1.92 (7)2.569 (5)120 (5)
O1—H1O···O2i0.98 (8)1.80 (8)2.753 (4)163 (7)

Symmetry codes: (i) x−1, y, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IS2398).

References

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