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

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

doi:10.1107/S1600536808044218

organic compounds

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ISSN: 2056-9890

Volume 65| Part 2| February 2009| Page o270

doi:10.1107/S1600536808044218

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

Shu-Na Luo,^a Lu Chen,^a Yu-Xing Gao,^a Peng-Xiang Xu ^a ^* and Yu-Fen Zhao ^a

^aDepartment of Chemistry and the Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, People's Republic of China
^*Correspondence e-mail: xpengxiang@xmu.edu.cn

(Received 5 September 2008; accepted 30 December 2008; online 10 January 2009)

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.

Related literature

For background, see: Nakamura et al. (1998 ). For the n-butyl analogue, see: Qian et al. (2006 ).

Experimental

Crystal data

C₁₆H₁₇NO₃
M_r = 271.31
Orthorhombic, P 2₁ 2₁ 2₁
a = 5.1589 (2) Å
b = 15.1430 (4) Å
c = 18.6367 (6) Å
V = 1455.92 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 (2) K
0.25 × 0.22 × 0.18 mm

Data collection

Bruker SMART APEX area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ) T_min = 0.979, T_max = 0.985
8138 measured reflections
1672 independent reflections
1172 reflections with I > 2σ(I)
R_int = 0.031

Refinement

R[F² > 2σ(F²)] = 0.032
wR(F²) = 0.076
S = 0.93
1672 reflections
193 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.08 e Å⁻³
Δρ_min = −0.10 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O3—H3⋯N1ⁱ	0.93 (3)	1.82 (3)	2.718 (3)	163 (2)
N1—H1A⋯O1ⁱⁱ	0.88 (2)	2.21 (3)	3.030 (3)	156 (2)
Symmetry codes: (i) $[-x+2, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]$ .

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; 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.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808044218/wk2093sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808044218/wk2093Isup2.hkl

checkCIF report

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.

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

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

C₁₆H₁₇NO₃	F(000) = 576
M_r = 271.31	D_x = 1.238 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 2651 reflections
a = 5.1589 (2) Å	θ = 2.7–32.7°
b = 15.1430 (4) Å	µ = 0.09 mm⁻¹
c = 18.6367 (6) Å	T = 293 K
V = 1455.92 (8) Å³	Plate, colorless
Z = 4	0.25 × 0.22 × 0.18 mm

Data collection top

Bruker APEX area-detector diffractometer	1672 independent reflections
Radiation source: fine-focus sealed tube	1172 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.031
ϕ and ω scans	θ_max = 26.0°, θ_min = 2.7°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −5→6
T_min = 0.979, T_max = 0.985	k = −18→16
8138 measured reflections	l = −22→22

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.032	Hydrogen site location: geom CH, N and OH from difmap
wR(F²) = 0.076	H atoms treated by a mixture of independent and constrained refinement
S = 0.93	w = 1/[σ²(F_o²) + (0.0454P)²] where P = (F_o² + 2F_c²)/3
1672 reflections	(Δ/σ)_max < 0.001
193 parameters	Δρ_max = 0.08 e Å⁻³
0 restraints	Δρ_min = −0.10 e Å⁻³

Crystal data top

C₁₆H₁₇NO₃	V = 1455.92 (8) Å³
M_r = 271.31	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 5.1589 (2) Å	µ = 0.09 mm⁻¹
b = 15.1430 (4) Å	T = 293 K
c = 18.6367 (6) Å	0.25 × 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)
T_min = 0.979, T_max = 0.985	R_int = 0.031
8138 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.032	0 restraints
wR(F²) = 0.076	H atoms treated by a mixture of independent and constrained refinement
S = 0.93	Δρ_max = 0.08 e Å⁻³
1672 reflections	Δρ_min = −0.10 e Å⁻³
193 parameters

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
O1	0.4947 (3)	0.30756 (10)	0.45476 (9)	0.0650 (5)
O2	0.8528 (3)	0.38687 (8)	0.43244 (8)	0.0538 (4)
O3	0.7826 (4)	0.60066 (9)	0.17256 (9)	0.0648 (5)
N1	0.7847 (5)	0.15910 (11)	0.39585 (11)	0.0499 (5)
C1	0.7006 (4)	0.31643 (12)	0.42536 (11)	0.0451 (5)
C2	0.8176 (4)	0.25132 (12)	0.37341 (10)	0.0441 (5)
H2A	1.0032	0.2638	0.3688	0.053*
C3	0.6894 (5)	0.26200 (12)	0.29951 (11)	0.0564 (6)
H3B	0.7642	0.2188	0.2672	0.068*
H3C	0.5065	0.2484	0.3042	0.068*
C4	0.7151 (5)	0.35192 (13)	0.26566 (11)	0.0491 (5)
C5	0.9175 (5)	0.37134 (14)	0.21981 (12)	0.0598 (6)
H5A	1.0392	0.3278	0.2096	0.072*
C6	0.9440 (5)	0.45339 (13)	0.18877 (12)	0.0558 (6)
H6A	1.0822	0.4644	0.1580	0.067*
C7	0.7680 (4)	0.51880 (12)	0.20290 (11)	0.0470 (5)
C8	0.5653 (5)	0.50079 (14)	0.24802 (13)	0.0591 (6)
H8A	0.4431	0.5443	0.2578	0.071*
C9	0.5413 (5)	0.41866 (15)	0.27908 (12)	0.0593 (6)
H9A	0.4034	0.4081	0.3100	0.071*
C10	0.7522 (5)	0.45997 (13)	0.47444 (13)	0.0634 (6)
H10A	0.7322	0.4426	0.5242	0.076*
H10B	0.5845	0.4782	0.4562	0.076*
C11	0.9434 (5)	0.53384 (13)	0.46821 (13)	0.0531 (6)
C12	1.0032 (7)	0.56917 (19)	0.40256 (15)	0.0943 (10)
H12A	0.9254	0.5469	0.3613	0.113*
C13	1.1791 (9)	0.6379 (2)	0.39742 (18)	0.1095 (12)
H13A	1.2166	0.6621	0.3527	0.131*
C14	1.2967 (7)	0.67010 (17)	0.4564 (2)	0.0909 (9)
H14A	1.4155	0.7161	0.4526	0.109*
C15	1.2409 (7)	0.63529 (17)	0.52081 (19)	0.0889 (9)
H15A	1.3218	0.6573	0.5617	0.107*
C16	1.0650 (6)	0.56733 (15)	0.52689 (14)	0.0687 (7)
H16A	1.0287	0.5439	0.5719	0.082*
H1A	0.816 (5)	0.1545 (14)	0.4419 (14)	0.060 (7)*
H1B	0.613 (7)	0.1410 (17)	0.3878 (16)	0.091 (9)*
H3	0.941 (6)	0.6089 (16)	0.1494 (15)	0.094 (10)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0604 (10)	0.0618 (9)	0.0728 (11)	−0.0057 (8)	0.0199 (9)	−0.0112 (8)
O2	0.0563 (8)	0.0399 (7)	0.0652 (9)	−0.0023 (7)	0.0044 (8)	−0.0138 (7)
O3	0.0676 (11)	0.0502 (8)	0.0766 (11)	0.0065 (8)	0.0092 (10)	0.0187 (8)
N1	0.0652 (13)	0.0378 (9)	0.0467 (11)	−0.0001 (9)	−0.0009 (11)	0.0004 (8)
C1	0.0508 (12)	0.0408 (11)	0.0437 (11)	0.0019 (10)	−0.0031 (12)	−0.0007 (9)
C2	0.0483 (11)	0.0380 (10)	0.0460 (11)	−0.0029 (9)	0.0014 (11)	−0.0021 (9)
C3	0.0777 (15)	0.0465 (11)	0.0451 (11)	−0.0146 (11)	−0.0028 (13)	0.0018 (10)
C4	0.0586 (13)	0.0472 (11)	0.0415 (10)	−0.0079 (11)	−0.0026 (12)	−0.0003 (10)
C5	0.0699 (15)	0.0461 (12)	0.0635 (14)	0.0064 (12)	0.0128 (13)	0.0032 (11)
C6	0.0559 (13)	0.0546 (12)	0.0570 (14)	0.0007 (12)	0.0147 (12)	0.0098 (12)
C7	0.0496 (12)	0.0444 (11)	0.0471 (11)	−0.0031 (10)	−0.0049 (12)	0.0088 (10)
C8	0.0538 (14)	0.0585 (13)	0.0649 (14)	0.0130 (12)	0.0075 (14)	0.0120 (12)
C9	0.0514 (13)	0.0703 (15)	0.0563 (14)	−0.0020 (12)	0.0105 (12)	0.0134 (12)
C10	0.0730 (16)	0.0474 (11)	0.0698 (13)	0.0002 (13)	0.0112 (15)	−0.0183 (11)
C11	0.0631 (14)	0.0418 (11)	0.0544 (13)	0.0020 (11)	0.0010 (13)	−0.0077 (10)
C12	0.138 (3)	0.0831 (18)	0.0616 (17)	−0.036 (2)	−0.002 (2)	−0.0094 (15)
C13	0.163 (4)	0.088 (2)	0.0770 (19)	−0.036 (2)	0.021 (2)	0.0098 (18)
C14	0.106 (2)	0.0549 (14)	0.111 (2)	−0.0181 (16)	0.009 (2)	−0.0092 (17)
C15	0.104 (2)	0.0669 (16)	0.096 (2)	−0.0152 (18)	−0.025 (2)	−0.0109 (17)
C16	0.0863 (18)	0.0553 (14)	0.0645 (15)	−0.0028 (14)	−0.0128 (16)	−0.0006 (13)

Geometric parameters (Å, º) top

O1—C1	1.203 (2)	C6—H6A	0.9300
O2—C1	1.331 (2)	C7—C8	1.369 (3)
O2—C10	1.452 (2)	C8—C9	1.377 (3)
O3—C7	1.365 (2)	C8—H8A	0.9300
O3—H3	0.93 (3)	C9—H9A	0.9300
N1—C2	1.467 (3)	C10—C11	1.496 (3)
N1—H1A	0.88 (2)	C10—H10A	0.9700
N1—H1B	0.94 (3)	C10—H10B	0.9700
C1—C2	1.508 (3)	C11—C16	1.359 (3)
C2—C3	1.536 (3)	C11—C12	1.371 (4)
C2—H2A	0.9800	C12—C13	1.384 (5)
C3—C4	1.506 (3)	C12—H12A	0.9300
C3—H3B	0.9700	C13—C14	1.348 (5)
C3—H3C	0.9700	C13—H13A	0.9300
C4—C9	1.374 (3)	C14—C15	1.341 (4)
C4—C5	1.381 (3)	C14—H14A	0.9300
C5—C6	1.377 (3)	C15—C16	1.377 (4)
C5—H5A	0.9300	C15—H15A	0.9300
C6—C7	1.369 (3)	C16—H16A	0.9300

C1—O2—C10	116.97 (16)	C8—C7—C6	118.71 (18)
C7—O3—H3	111.3 (16)	C7—C8—C9	120.4 (2)
C2—N1—H1A	109.5 (15)	C7—C8—H8A	119.8
C2—N1—H1B	109.9 (16)	C9—C8—H8A	119.8
H1A—N1—H1B	108 (3)	C4—C9—C8	121.9 (2)
O1—C1—O2	124.43 (19)	C4—C9—H9A	119.0
O1—C1—C2	124.95 (19)	C8—C9—H9A	119.0
O2—C1—C2	110.58 (18)	O2—C10—C11	107.02 (19)
N1—C2—C1	113.15 (16)	O2—C10—H10A	110.3
N1—C2—C3	107.82 (16)	C11—C10—H10A	110.3
C1—C2—C3	109.55 (17)	O2—C10—H10B	110.3
N1—C2—H2A	108.7	C11—C10—H10B	110.3
C1—C2—H2A	108.7	H10A—C10—H10B	108.6
C3—C2—H2A	108.7	C16—C11—C12	118.0 (2)
C4—C3—C2	115.65 (16)	C16—C11—C10	121.4 (2)
C4—C3—H3B	108.4	C12—C11—C10	120.6 (2)
C2—C3—H3B	108.4	C11—C12—C13	120.2 (3)
C4—C3—H3C	108.4	C11—C12—H12A	119.9
C2—C3—H3C	108.4	C13—C12—H12A	119.9
H3B—C3—H3C	107.4	C14—C13—C12	120.7 (3)
C9—C4—C5	116.71 (19)	C14—C13—H13A	119.6
C9—C4—C3	122.1 (2)	C12—C13—H13A	119.6
C5—C4—C3	121.2 (2)	C15—C14—C13	119.4 (3)
C6—C5—C4	121.8 (2)	C15—C14—H14A	120.3
C6—C5—H5A	119.1	C13—C14—H14A	120.3
C4—C5—H5A	119.1	C14—C15—C16	120.6 (3)
C7—C6—C5	120.4 (2)	C14—C15—H15A	119.7
C7—C6—H6A	119.8	C16—C15—H15A	119.7
C5—C6—H6A	119.8	C11—C16—C15	121.1 (3)
O3—C7—C8	118.5 (2)	C11—C16—H16A	119.4
O3—C7—C6	122.7 (2)	C15—C16—H16A	119.4

C10—O2—C1—O1	−4.7 (3)	C6—C7—C8—C9	0.7 (3)
C10—O2—C1—C2	173.19 (16)	C5—C4—C9—C8	0.6 (3)
O1—C1—C2—N1	−41.7 (3)	C3—C4—C9—C8	−180.0 (2)
O2—C1—C2—N1	140.49 (19)	C7—C8—C9—C4	−0.8 (4)
O1—C1—C2—C3	78.7 (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—C12	59.8 (3)
C1—C2—C3—C4	59.4 (3)	C16—C11—C12—C13	−1.1 (4)
C2—C3—C4—C9	−87.4 (3)	C10—C11—C12—C13	179.6 (3)
C2—C3—C4—C5	92.1 (2)	C11—C12—C13—C14	1.0 (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—C7	0.1 (4)	C12—C11—C16—C15	0.7 (4)
C5—C6—C7—O3	−178.8 (2)	C10—C11—C16—C15	179.9 (2)
C5—C6—C7—C8	−0.3 (3)	C14—C15—C16—C11	−0.1 (4)
O3—C7—C8—C9	179.2 (2)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···N1ⁱ	0.93 (3)	1.82 (3)	2.718 (3)	163 (2)
N1—H1A···O1ⁱⁱ	0.88 (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.

Experimental details

Crystal data
Chemical formula	C₁₆H₁₇NO₃
M_r	271.31
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	293
a, b, c (Å)	5.1589 (2), 15.1430 (4), 18.6367 (6)
V (Å³)	1455.92 (8)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.25 × 0.22 × 0.18

Data collection
Diffractometer	Bruker APEX area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.979, 0.985
No. of measured, independent and observed [I > 2σ(I)] reflections	8138, 1672, 1172
R_int	0.031
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.032, 0.076, 0.93
No. of reflections	1672
No. of parameters	193
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.08, −0.10

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2001), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···N1ⁱ	0.93 (3)	1.82 (3)	2.718 (3)	163 (2)
N1—H1A···O1ⁱⁱ	0.88 (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

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

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