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Acta Cryst. (2009). E65, o270    [ doi:10.1107/S1600536808044218 ]

(S)-Benzyl 2-amino-3-(4-hydroxyphenyl)propanoate

S.-N. Luo, L. Chen, Y.-X. Gao, P.-X. Xu and Y.-F. Zhao

Abstract top

The title compound, C16H17NO3, adopts a folded conformation in the crystal structure. The crystal packing is stabilized by intermolecular O-H...O and N-H...O hydrogen-bonding interactions. The absolute configuration was assigned assuming that the absolute configuration of the starting material L-tyrosine was retained during the synthesis.

Comment top

The title compound, (I), is a valuable protected amino acid, which is used not only for polypeptide synthesis but also for the synthesis of (4-Boronophenyl)alanine (BPA), which is clinically used for the treatment of malignant melanoma (Nakamura et al., 1998).

The molecular structure of (I) is shown in Fig. 1. The molecule adopts a somewhat folded or U-shaped conformation as evidenced in the C1/C2/C3/C4 torsion angle of 58.9 (3)°. Despite the adoption of this conformation, there is no evidence for significant intramolecular C—H···π interactions. In terms of geometric parameters and overall conformation, the structure of (I) resembles that of the n-butyl analogue (Qian et al., 2006). Hydrogen bonding plays a significant role in stabilizing the crystal structure; see Table 1 for geometric parameters and symmetry operations. The most prominent link occurs between the phenol H and the amine N atoms, to form chains along the c axis. Molecules are connected into a three-dimensional array by O—H···O and N—H···O intermolecular hydrogen-bonding interactions. The absolute configuration of (I) was assigned assuming that the absolute configuration of the starting material L-tyrosine was retained during the synthesis.

Related literature top

For related literature, see: Nakamura et al. (1998); Qian et al. (2006).

Experimental top

To a solution of L-tyrosine (10 g, 55 mmol) and benzyl alcohol (25 ml) in benzene (120 ml) was added p-toluenesulfonic acid monohydrate (12.6 g, 66 mmol) at room temperature. The water generated in the reaction was separated by benzene azeotropic distillation for 3 h, and the white precipitate was filtered off. The filtrate was washed with sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered and concentrated. Purification by recrystallization from ethanol gave the titled compound as a white solid (12 g). Single crystals of (I) were obtained by slow evaporation of an ethyl acetate solution.

Refinement top

The H atoms were positioned geometrically (C—H = 0.93, 0.98 or 0.97 Å for phenyl, methine or methylene H atoms, respectively) and were included in the refinement in the riding-model approximation. The isotropic displacement parameters were set at 1.2 times Ueq of the parent atoms. The NH and OH positions were located from difference Fourier maps and their positions and an isotropic displacement parameter refined. In the absence of significant anomalous scattering effects, Friedel pairs were merged.

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SMART (Bruker, 2001); data reduction: SAINT (Bruker, 2001); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), showing 50% probability displacement ellipsoids (arbitrary spheres for H atoms).
(S)-Benzyl 2-amino-3-(4-hydroxyphenyl)propanoate top
Crystal data top
C16H17NO3F(000) = 576
Mr = 271.31Dx = 1.238 Mg m−3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 2651 reflections
a = 5.1589 (2) Åθ = 2.7–32.7°
b = 15.1430 (4) ŵ = 0.09 mm−1
c = 18.6367 (6) ÅT = 293 K
V = 1455.92 (8) Å3Plate, colorless
Z = 40.25 × 0.22 × 0.18 mm
Data collection top
Bruker APEX area-detector
diffractometer		1672 independent reflections
Radiation source: fine-focus sealed tube1172 reflections with I > 2σ(I)
graphiteRint = 0.031
φ and ω scansθmax = 26.0°, θmin = 2.7°
Absorption correction: multi-scan
(SADABS; Bruker, 2001)		h = −5→6
Tmin = 0.979, Tmax = 0.985k = −18→16
8138 measured reflectionsl = −22→22
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.032Hydrogen site location: geom CH, N and OH from difmap
wR(F2) = 0.076H atoms treated by a mixture of independent and constrained refinement
S = 0.93 w = 1/[σ2(Fo2) + (0.0454P)2]
where P = (Fo2 + 2Fc2)/3
1672 reflections(Δ/σ)max < 0.001
193 parametersΔρmax = 0.08 e Å−3
0 restraintsΔρmin = −0.10 e Å−3
Crystal data top
C16H17NO3V = 1455.92 (8) Å3
Mr = 271.31Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 5.1589 (2) ŵ = 0.09 mm−1
b = 15.1430 (4) ÅT = 293 K
c = 18.6367 (6) Å0.25 × 0.22 × 0.18 mm
Data collection top
Bruker APEX area-detector
diffractometer		1672 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2001)		1172 reflections with I > 2σ(I)
Tmin = 0.979, Tmax = 0.985Rint = 0.031
8138 measured reflectionsθmax = 26.0°
Refinement top
R[F2 > 2σ(F2)] = 0.032H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.076Δρmax = 0.08 e Å−3
S = 0.93Δρmin = −0.10 e Å−3
1672 reflectionsAbsolute structure: ?
193 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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
O10.4947 (3)0.30756 (10)0.45476 (9)0.0650 (5)
O20.8528 (3)0.38687 (8)0.43244 (8)0.0538 (4)
O30.7826 (4)0.60066 (9)0.17256 (9)0.0648 (5)
N10.7847 (5)0.15910 (11)0.39585 (11)0.0499 (5)
C10.7006 (4)0.31643 (12)0.42536 (11)0.0451 (5)
C20.8176 (4)0.25132 (12)0.37341 (10)0.0441 (5)
H2A1.00320.26380.36880.053*
C30.6894 (5)0.26200 (12)0.29951 (11)0.0564 (6)
H3B0.76420.21880.26720.068*
H3C0.50650.24840.30420.068*
C40.7151 (5)0.35192 (13)0.26566 (11)0.0491 (5)
C50.9175 (5)0.37134 (14)0.21981 (12)0.0598 (6)
H5A1.03920.32780.20960.072*
C60.9440 (5)0.45339 (13)0.18877 (12)0.0558 (6)
H6A1.08220.46440.15800.067*
C70.7680 (4)0.51880 (12)0.20290 (11)0.0470 (5)
C80.5653 (5)0.50079 (14)0.24802 (13)0.0591 (6)
H8A0.44310.54430.25780.071*
C90.5413 (5)0.41866 (15)0.27908 (12)0.0593 (6)
H9A0.40340.40810.31000.071*
C100.7522 (5)0.45997 (13)0.47444 (13)0.0634 (6)
H10A0.73220.44260.52420.076*
H10B0.58450.47820.45620.076*
C110.9434 (5)0.53384 (13)0.46821 (13)0.0531 (6)
C121.0032 (7)0.56917 (19)0.40256 (15)0.0943 (10)
H12A0.92540.54690.36130.113*
C131.1791 (9)0.6379 (2)0.39742 (18)0.1095 (12)
H13A1.21660.66210.35270.131*
C141.2967 (7)0.67010 (17)0.4564 (2)0.0909 (9)
H14A1.41550.71610.45260.109*
C151.2409 (7)0.63529 (17)0.52081 (19)0.0889 (9)
H15A1.32180.65730.56170.107*
C161.0650 (6)0.56733 (15)0.52689 (14)0.0687 (7)
H16A1.02870.54390.57190.082*
H1A0.816 (5)0.1545 (14)0.4419 (14)0.060 (7)*
H1B0.613 (7)0.1410 (17)0.3878 (16)0.091 (9)*
H30.941 (6)0.6089 (16)0.1494 (15)0.094 (10)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0604 (10)0.0618 (9)0.0728 (11)−0.0057 (8)0.0199 (9)−0.0112 (8)
O20.0563 (8)0.0399 (7)0.0652 (9)−0.0023 (7)0.0044 (8)−0.0138 (7)
O30.0676 (11)0.0502 (8)0.0766 (11)0.0065 (8)0.0092 (10)0.0187 (8)
N10.0652 (13)0.0378 (9)0.0467 (11)−0.0001 (9)−0.0009 (11)0.0004 (8)
C10.0508 (12)0.0408 (11)0.0437 (11)0.0019 (10)−0.0031 (12)−0.0007 (9)
C20.0483 (11)0.0380 (10)0.0460 (11)−0.0029 (9)0.0014 (11)−0.0021 (9)
C30.0777 (15)0.0465 (11)0.0451 (11)−0.0146 (11)−0.0028 (13)0.0018 (10)
C40.0586 (13)0.0472 (11)0.0415 (10)−0.0079 (11)−0.0026 (12)−0.0003 (10)
C50.0699 (15)0.0461 (12)0.0635 (14)0.0064 (12)0.0128 (13)0.0032 (11)
C60.0559 (13)0.0546 (12)0.0570 (14)0.0007 (12)0.0147 (12)0.0098 (12)
C70.0496 (12)0.0444 (11)0.0471 (11)−0.0031 (10)−0.0049 (12)0.0088 (10)
C80.0538 (14)0.0585 (13)0.0649 (14)0.0130 (12)0.0075 (14)0.0120 (12)
C90.0514 (13)0.0703 (15)0.0563 (14)−0.0020 (12)0.0105 (12)0.0134 (12)
C100.0730 (16)0.0474 (11)0.0698 (13)0.0002 (13)0.0112 (15)−0.0183 (11)
C110.0631 (14)0.0418 (11)0.0544 (13)0.0020 (11)0.0010 (13)−0.0077 (10)
C120.138 (3)0.0831 (18)0.0616 (17)−0.036 (2)−0.002 (2)−0.0094 (15)
C130.163 (4)0.088 (2)0.0770 (19)−0.036 (2)0.021 (2)0.0098 (18)
C140.106 (2)0.0549 (14)0.111 (2)−0.0181 (16)0.009 (2)−0.0092 (17)
C150.104 (2)0.0669 (16)0.096 (2)−0.0152 (18)−0.025 (2)−0.0109 (17)
C160.0863 (18)0.0553 (14)0.0645 (15)−0.0028 (14)−0.0128 (16)−0.0006 (13)
Geometric parameters (Å, °) top
O1—C11.203 (2)C6—H6A0.9300
O2—C11.331 (2)C7—C81.369 (3)
O2—C101.452 (2)C8—C91.377 (3)
O3—C71.365 (2)C8—H8A0.9300
O3—H30.93 (3)C9—H9A0.9300
N1—C21.467 (3)C10—C111.496 (3)
N1—H1A0.88 (2)C10—H10A0.9700
N1—H1B0.94 (3)C10—H10B0.9700
C1—C21.508 (3)C11—C161.359 (3)
C2—C31.536 (3)C11—C121.371 (4)
C2—H2A0.9800C12—C131.384 (5)
C3—C41.506 (3)C12—H12A0.9300
C3—H3B0.9700C13—C141.348 (5)
C3—H3C0.9700C13—H13A0.9300
C4—C91.374 (3)C14—C151.341 (4)
C4—C51.381 (3)C14—H14A0.9300
C5—C61.377 (3)C15—C161.377 (4)
C5—H5A0.9300C15—H15A0.9300
C6—C71.369 (3)C16—H16A0.9300
C1—O2—C10116.97 (16)C8—C7—C6118.71 (18)
C7—O3—H3111.3 (16)C7—C8—C9120.4 (2)
C2—N1—H1A109.5 (15)C7—C8—H8A119.8
C2—N1—H1B109.9 (16)C9—C8—H8A119.8
H1A—N1—H1B108 (3)C4—C9—C8121.9 (2)
O1—C1—O2124.43 (19)C4—C9—H9A119.0
O1—C1—C2124.95 (19)C8—C9—H9A119.0
O2—C1—C2110.58 (18)O2—C10—C11107.02 (19)
N1—C2—C1113.15 (16)O2—C10—H10A110.3
N1—C2—C3107.82 (16)C11—C10—H10A110.3
C1—C2—C3109.55 (17)O2—C10—H10B110.3
N1—C2—H2A108.7C11—C10—H10B110.3
C1—C2—H2A108.7H10A—C10—H10B108.6
C3—C2—H2A108.7C16—C11—C12118.0 (2)
C4—C3—C2115.65 (16)C16—C11—C10121.4 (2)
C4—C3—H3B108.4C12—C11—C10120.6 (2)
C2—C3—H3B108.4C11—C12—C13120.2 (3)
C4—C3—H3C108.4C11—C12—H12A119.9
C2—C3—H3C108.4C13—C12—H12A119.9
H3B—C3—H3C107.4C14—C13—C12120.7 (3)
C9—C4—C5116.71 (19)C14—C13—H13A119.6
C9—C4—C3122.1 (2)C12—C13—H13A119.6
C5—C4—C3121.2 (2)C15—C14—C13119.4 (3)
C6—C5—C4121.8 (2)C15—C14—H14A120.3
C6—C5—H5A119.1C13—C14—H14A120.3
C4—C5—H5A119.1C14—C15—C16120.6 (3)
C7—C6—C5120.4 (2)C14—C15—H15A119.7
C7—C6—H6A119.8C16—C15—H15A119.7
C5—C6—H6A119.8C11—C16—C15121.1 (3)
O3—C7—C8118.5 (2)C11—C16—H16A119.4
O3—C7—C6122.7 (2)C15—C16—H16A119.4
C10—O2—C1—O1−4.7 (3)C6—C7—C8—C90.7 (3)
C10—O2—C1—C2173.19 (16)C5—C4—C9—C80.6 (3)
O1—C1—C2—N1−41.7 (3)C3—C4—C9—C8−180.0 (2)
O2—C1—C2—N1140.49 (19)C7—C8—C9—C4−0.8 (4)
O1—C1—C2—C378.7 (2)C1—O2—C10—C11−174.17 (19)
O2—C1—C2—C3−99.2 (2)O2—C10—C11—C16−119.4 (2)
N1—C2—C3—C4−177.03 (19)O2—C10—C11—C1259.8 (3)
C1—C2—C3—C459.4 (3)C16—C11—C12—C13−1.1 (4)
C2—C3—C4—C9−87.4 (3)C10—C11—C12—C13179.6 (3)
C2—C3—C4—C592.1 (2)C11—C12—C13—C141.0 (6)
C9—C4—C5—C6−0.2 (3)C12—C13—C14—C15−0.3 (6)
C3—C4—C5—C6−179.7 (2)C13—C14—C15—C16−0.1 (5)
C4—C5—C6—C70.1 (4)C12—C11—C16—C150.7 (4)
C5—C6—C7—O3−178.8 (2)C10—C11—C16—C15179.9 (2)
C5—C6—C7—C8−0.3 (3)C14—C15—C16—C11−0.1 (4)
O3—C7—C8—C9179.2 (2)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O3—H3···N1i0.93 (3)1.82 (3)2.718 (3)163 (2)
N1—H1A···O1ii0.88 (2)2.21 (3)3.030 (3)156 (2)
Symmetry codes: (i) −x+2, y+1/2, −z+1/2; (ii) x+1/2, −y+1/2, −z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
O3—H3···N1i0.93 (3)1.82 (3)2.718 (3)163 (2)
N1—H1A···O1ii0.88 (2)2.21 (3)3.030 (3)156 (2)
Symmetry codes: (i) −x+2, y+1/2, −z+1/2; (ii) x+1/2, −y+1/2, −z+1.
Acknowledgements top

The authors thank the Major Programme of the National Natural Science Foundation of China (grant No. 20732004) for supporting this work, and Mr. R.-B.Huang for technical assistance.

references
References top

Bruker (2001). SAINT, SMART and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.

Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.

Nakamura, H., Fujiwara, M. & Yamamoto, Y. (1998). J. Org. Chem. 63, 7529–7530.

Qian, S.-S., Zhu, H.-L. & Tiekink, E. R. T. (2006). Acta Cryst. E62, o882–o884.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.