Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270107043296/dn3056sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S0108270107043296/dn3056IIsup2.hkl |
CCDC reference: 677219
For related literature, see: Allen (1986); Asanuma et al. (2006); Breuer et al. (2004); Brough & McInally (2004); Flack (1983); Guillot et al. (2001); Jelsch et al. (1998, 2005); Kashida et al. (2006a, 2006b); Peng et al. (2006); Pichon-Pesme, Jelsch, Guillot & Lecomte (2004); Shi et al. (2005); Villorbina et al. (2007); Waykole et al. (2007); Yoshida et al. (1988); Zarychta et al. (2007).
For the preparation of (2R,3S)-2-N,N-dibenzylamino-3-hydroxybenzylbutanoate, (I), benzyl bromide (6.6 ml, 18.5 mmol, 3.3 equivalents) was dropped over a period of 30 min onto a magnetically stirred dispersion of 98% D-threonine (2.02 g, 16.6 mmol) and Na2CO3 (3.875 g, 19.5 mmol, ~2.2 equivalents) in 75% aqueous EtOH (50 ml) at room temperature. The resulting mixture was then refluxed for 2.5 h [the formation of (I) being monitored by SiO2 thin-layer chromatography (TLC); Rf = 0.43; AcOEt–cyclohexane 1:4], cooled to room temperature, concentrated under reduced pressure, and partitioned between CH2Cl2 and water (2 × 50 ml). The aqueous phase was extracted with CH2Cl2 (3 × 50 ml). The combined organic phases were washed with saturated aqueous NaHCO3 (50 ml) and water (3 × 50 ml), dried over MgSO4, and finally concentrated in vacuo to afford the crude ester (I) as a pale-yellow syrup, which was used for the next step without further purification (yield 5.8 g, 14.9 mmol, ~90%). An analytical sample was isolated by TLC (SiO2, AcOEt–hexane 1:9) as a colourless gum. [α]D=+148.9° (c = 2.6, CHCl3). MS (70 eV, EI+) calculated for C25H27NO3 (389); found m/z (%) = 390 (23) [M+H]+, 344 (32) [M—C2H5O]+. IR (film): 1730 cm-1; 1H NMR (250 MHz, CDCl3, 298 K, p.p.m): δ 7.15–7.55 (15H, m, aromatic), 5.35 (1H, d, J = 12.4 Hz, CHHPh), 5.22 (1H, d, CHHPh), 4.07 (1H, m, H-b), 4.07 (2H, d, J = 13.2 Hz, NCHHPh), 3.5 (1H, s, OH), 3.39 (2H, d, NCHHPh), 3.11 (1H, d, J = 9.5 Hz, H-α), 1.1 (3H, d, J = 5.8 Hz, CH3). 13C NMR (100 MHz, CDCl3, p.p.m.): δ 139.45 (C aromatic), 135.7 (C aromatic), 129.1, 128.7, 128.6, 128.5, 127.4 (CH aromatic), 67.2 (C-β), 66.3 (PhCH2O), 63.2 (C-α), 54.8 (PhCH2N), 19.2 (CH3). Elemental analysis calculated for C25H27NO3 (389.49): C 77.09, H 6.99, N 3.60%; found: C 76.91, H 6.81, N 3.67%.
For the preparation of (II), to a magnetically stirred suspension of 95% LiAlH4 (0.78 g, ~19.5 mmol, 1.15 equivalents) in absolute THF (50 ml) under Ar cooled below 277 K was dropped a solution of crude ester (I) (5.453 g, 14.0 mmol) in absolute ether (50 ml) over a period of 30 min. The mixture was then stirred for 25 h at room temperature and refluxed for one additional hour. After completion of the reaction (checked by SiO2 TLC; ethyl acetate–n-hexane 1:1; Rf ≈ 0.29), the mixture was cooled to room temperature, quenched by slow addition of ethyl acetate (5 ml) and saturated aqueous Na2SO4 (5 ml), and stirred overnight in air. The suspension was filtrated through a sintered glass and the remaining salts thoroughly washed with a CH2Cl2–ethanol mixture (1:1, 100 ml). The filtrates were concentrated under reduced pressure and the residue partioned in CH2Cl2 –water (2 × 50 ml), washed with water (2× 20 ml), dried over MgSO4, concentrated under reduced pressure, and finally stored at 277 K. The resulting solids were isolated by filtration and crystallized twice from ethyl acetate–hexanes (1:19) to yield pure alcohol (II) (3.2 g, ~73%) as white crystals suitable for X-ray diffraction (m.p. 363–364 K; Tottoli). [α]D=+54.0° (c = 1, CHCl3). MS (70 eV, EI+): m/z 286.1 [M + H]+. 1H NMR (250 MHz, CDCl3/ε, D2O, p.p.m.): δ 7.2–7.42 (m, 10H, aromatic), 3.99 (2H, d, J = 13.2 Hz, NCHHPh), 3.85 (1H, m, H-b), 3.8 (2H, d, J = 13.2 Hz, J = 5.8 Hz, CH2OD), 3.72 (2H, d, NCHHPh), 2.61 (1H, d, J = 8.8 Hz, H-a), 1.15 (3H, d, J = 5.8 Hz, CH3).13C NMR (100 MHz, CDCl3, p.p.m.): δ 139.5 (C aromatic), 129.4, 128.7, 127.5 (CH aromatic), 65.5 (C-b), 64.8 (C-a); 59.1 (PhCH2), 54.7 (CH2—OH), 20.4 (CH3). Elemental analysis calculated for C18H23NO2 (285.39): C 75.76, H 8.12, N 4.91%; found: C 75.79, H 8.09, N 4.90%.
At first, a least-squares refinement, based on |F2|, was performed with program SHELXL-97(Sheldrick, 1997), the hydrogen atoms being constrained according to standard X-ray crystallography stereochemistry. Then a least-squares refinement, based on |F|, was carried out with the program MoPro (Guillot et al., 2001, Jelsch et al., 2005) using the ELMAM multipolar-atom model (Zarychta et al., 2007). The reflection weights were set equal to 1/σ2(Fo). The Uiso(H) values were restrained to be 1.2Ueq of the attached atom with a standard deviation of 0.01 Å. In the absence of suitable anomalous scattering, the refinement of the Flack (1983) parameter led to inconclusive values; therefore Friedel equivalent reflections were merged prior to the final refinements. The absolute structure was set by reference to the known chirality of the enantiomeric pure D-Threonine used in the chemical synthesis.
Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell refinement: CrysAlis RED (Oxford Diffraction, 2006); data reduction: CrysAlis RED (Oxford Diffraction, 2006); program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 1990); software used to prepare material for publication: publCIF (Westrip, 2007).
C18H23NO2 | F(000) = 616 |
Mr = 285.37 | Dx = 1.135 Mg m−3 |
Monoclinic, C2 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: C 2y | Cell parameters from 3216 reflections |
a = 18.6701 (4) Å | θ = 2.5–23.8° |
b = 6.652 (1) Å | µ = 0.07 mm−1 |
c = 16.060 (2) Å | T = 100 K |
β = 123.126 (8)° | Prismatic, colourless |
V = 1670.4 (3) Å3 | 0.35 × 0.25 × 0.20 mm |
Z = 4 |
Radiation source: fine-focus sealed tube | Rint = 0.000 |
Graphite monochromator | θmax = 27.4°, θmin = 3.7° |
2016 measured reflections | h = −23→20 |
2016 independent reflections | k = 0→8 |
1965 reflections with I > 2σ(I) | l = 0→20 |
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)] = 0.037 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.091 | H-atom parameters constrained |
S = 1.06 | w = 1/[σ2(Fo2) + (0.0542P)2 + 0.793P] where P = (Fo2 + 2Fc2)/3 |
2016 reflections | (Δ/σ)max < 0.001 |
193 parameters | Δρmax = 0.28 e Å−3 |
1 restraint | Δρmin = −0.16 e Å−3 |
C18H23NO2 | V = 1670.4 (3) Å3 |
Mr = 285.37 | Z = 4 |
Monoclinic, C2 | Mo Kα radiation |
a = 18.6701 (4) Å | µ = 0.07 mm−1 |
b = 6.652 (1) Å | T = 100 K |
c = 16.060 (2) Å | 0.35 × 0.25 × 0.20 mm |
β = 123.126 (8)° |
2016 measured reflections | 1965 reflections with I > 2σ(I) |
2016 independent reflections | Rint = 0.000 |
R[F2 > 2σ(F2)] = 0.037 | 1 restraint |
wR(F2) = 0.091 | H-atom parameters constrained |
S = 1.06 | Δρmax = 0.28 e Å−3 |
2016 reflections | Δρmin = −0.16 e Å−3 |
193 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.25356 (8) | −0.1501 (2) | 0.29809 (9) | 0.0237 (3) | |
H1 | 0.2024 | −0.1183 | 0.2564 | 0.036* | |
O2 | 0.23295 (8) | 0.53289 (19) | 0.39723 (10) | 0.0236 (3) | |
H2 | 0.2437 | 0.6071 | 0.3631 | 0.035* | |
N1 | 0.15196 (8) | 0.1614 (2) | 0.28283 (10) | 0.0160 (3) | |
C1 | 0.24683 (10) | 0.1972 (3) | 0.33879 (12) | 0.0155 (3) | |
H1A | 0.2608 | 0.2436 | 0.2900 | 0.019* | |
C2 | 0.29111 (10) | −0.0079 (3) | 0.38078 (12) | 0.0175 (3) | |
H2A | 0.2784 | −0.0548 | 0.4306 | 0.021* | |
C3 | 0.38880 (11) | −0.0072 (3) | 0.43024 (13) | 0.0252 (4) | |
H3A | 0.4105 | −0.1453 | 0.4469 | 0.038* | |
H3B | 0.4157 | 0.0738 | 0.4910 | 0.038* | |
H3C | 0.4024 | 0.0503 | 0.3842 | 0.038* | |
C4 | 0.28385 (10) | 0.3538 (3) | 0.42456 (12) | 0.0190 (3) | |
H4A | 0.2875 | 0.2919 | 0.4828 | 0.023* | |
H4B | 0.3425 | 0.3903 | 0.4443 | 0.023* | |
C5 | 0.11876 (10) | 0.1553 (3) | 0.34968 (12) | 0.0179 (3) | |
H5A | 0.1074 | 0.2942 | 0.3616 | 0.021* | |
H5B | 0.1631 | 0.0969 | 0.4146 | 0.021* | |
C6 | 0.03675 (10) | 0.0312 (3) | 0.30499 (12) | 0.0185 (3) | |
C7 | −0.03725 (11) | 0.1123 (3) | 0.29580 (12) | 0.0211 (4) | |
H7 | −0.0360 | 0.2460 | 0.3174 | 0.025* | |
C8 | −0.11264 (11) | −0.0016 (3) | 0.25519 (13) | 0.0257 (4) | |
H8 | −0.1617 | 0.0549 | 0.2498 | 0.031* | |
C9 | −0.11528 (12) | −0.1978 (3) | 0.22276 (13) | 0.0246 (4) | |
H9 | −0.1664 | −0.2744 | 0.1939 | 0.030* | |
C10 | −0.04146 (12) | −0.2811 (3) | 0.23326 (14) | 0.0249 (4) | |
H10 | −0.0427 | −0.4154 | 0.2124 | 0.030* | |
C11 | 0.03407 (11) | −0.1677 (3) | 0.27433 (13) | 0.0221 (4) | |
H11 | 0.0835 | −0.2261 | 0.2814 | 0.026* | |
C12 | 0.09796 (10) | 0.2986 (3) | 0.19620 (12) | 0.0183 (3) | |
H12A | 0.1044 | 0.4377 | 0.2212 | 0.022* | |
H12B | 0.0372 | 0.2599 | 0.1643 | 0.022* | |
C13 | 0.12040 (10) | 0.2954 (3) | 0.11695 (11) | 0.0178 (3) | |
C14 | 0.11466 (11) | 0.1178 (3) | 0.06579 (13) | 0.0224 (4) | |
H14 | 0.0976 | −0.0038 | 0.0811 | 0.027* | |
C15 | 0.13415 (12) | 0.1181 (3) | −0.00855 (14) | 0.0283 (4) | |
H15 | 0.1301 | −0.0032 | −0.0421 | 0.034* | |
C16 | 0.15915 (12) | 0.2953 (4) | −0.03249 (13) | 0.0283 (4) | |
H16 | 0.1725 | 0.2951 | −0.0817 | 0.034* | |
C17 | 0.16423 (12) | 0.4724 (4) | 0.01680 (13) | 0.0280 (4) | |
H17 | 0.1805 | 0.5940 | 0.0005 | 0.034* | |
C18 | 0.14513 (11) | 0.4725 (3) | 0.09166 (13) | 0.0224 (4) | |
H18 | 0.1492 | 0.5943 | 0.1249 | 0.027* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0249 (6) | 0.0181 (6) | 0.0245 (6) | 0.0035 (5) | 0.0111 (5) | −0.0015 (5) |
O2 | 0.0276 (6) | 0.0150 (6) | 0.0285 (6) | 0.0018 (5) | 0.0156 (5) | −0.0004 (5) |
N1 | 0.0139 (6) | 0.0177 (7) | 0.0163 (6) | 0.0010 (5) | 0.0081 (5) | 0.0016 (5) |
C1 | 0.0148 (7) | 0.0148 (8) | 0.0176 (7) | 0.0009 (6) | 0.0093 (6) | 0.0010 (6) |
C2 | 0.0192 (7) | 0.0155 (8) | 0.0186 (7) | 0.0027 (7) | 0.0109 (6) | 0.0019 (7) |
C3 | 0.0180 (8) | 0.0253 (9) | 0.0293 (9) | 0.0053 (7) | 0.0110 (7) | 0.0049 (8) |
C4 | 0.0184 (7) | 0.0163 (8) | 0.0203 (8) | −0.0005 (7) | 0.0093 (6) | −0.0009 (7) |
C5 | 0.0177 (7) | 0.0199 (8) | 0.0181 (7) | 0.0001 (7) | 0.0111 (6) | 0.0000 (7) |
C6 | 0.0186 (8) | 0.0216 (8) | 0.0168 (7) | 0.0002 (7) | 0.0105 (6) | 0.0019 (7) |
C7 | 0.0221 (8) | 0.0224 (8) | 0.0218 (8) | 0.0021 (7) | 0.0139 (7) | 0.0016 (7) |
C8 | 0.0194 (8) | 0.0345 (10) | 0.0268 (8) | 0.0016 (8) | 0.0149 (7) | 0.0032 (8) |
C9 | 0.0207 (8) | 0.0315 (10) | 0.0231 (8) | −0.0069 (8) | 0.0128 (7) | 0.0010 (8) |
C10 | 0.0275 (9) | 0.0214 (8) | 0.0276 (9) | −0.0035 (8) | 0.0163 (8) | −0.0005 (7) |
C11 | 0.0198 (8) | 0.0218 (9) | 0.0264 (8) | 0.0011 (7) | 0.0137 (7) | 0.0010 (7) |
C12 | 0.0180 (7) | 0.0184 (8) | 0.0175 (7) | 0.0036 (6) | 0.0091 (6) | 0.0022 (7) |
C13 | 0.0142 (7) | 0.0206 (8) | 0.0148 (7) | 0.0024 (6) | 0.0056 (6) | 0.0018 (7) |
C14 | 0.0227 (8) | 0.0202 (9) | 0.0207 (8) | 0.0006 (7) | 0.0095 (7) | −0.0008 (7) |
C15 | 0.0268 (9) | 0.0340 (11) | 0.0208 (8) | 0.0054 (8) | 0.0108 (7) | −0.0041 (8) |
C16 | 0.0219 (8) | 0.0441 (12) | 0.0191 (8) | 0.0048 (8) | 0.0115 (7) | 0.0028 (9) |
C17 | 0.0236 (9) | 0.0358 (11) | 0.0229 (8) | −0.0032 (8) | 0.0115 (7) | 0.0056 (8) |
C18 | 0.0229 (8) | 0.0212 (9) | 0.0205 (8) | −0.0003 (7) | 0.0101 (7) | 0.0001 (7) |
O1—C2 | 1.460 (2) | C7—H7 | 0.9500 |
O1—H1 | 0.8400 | C8—C9 | 1.396 (3) |
O2—C4 | 1.435 (2) | C8—H8 | 0.9500 |
O2—H2 | 0.8400 | C9—C10 | 1.407 (3) |
N1—C12 | 1.500 (2) | C9—H9 | 0.9500 |
N1—C1 | 1.504 (2) | C10—C11 | 1.406 (3) |
N1—C5 | 1.505 (2) | C10—H10 | 0.9500 |
C1—C2 | 1.546 (2) | C11—H11 | 0.9500 |
C1—C4 | 1.555 (2) | C12—C13 | 1.542 (2) |
C1—H1A | 1.0000 | C12—H12A | 0.9900 |
C2—C3 | 1.541 (2) | C12—H12B | 0.9900 |
C2—H2A | 1.0000 | C13—C18 | 1.403 (3) |
C3—H3A | 0.9800 | C13—C14 | 1.409 (2) |
C3—H3B | 0.9800 | C14—C15 | 1.426 (3) |
C3—H3C | 0.9800 | C14—H14 | 0.9500 |
C4—H4A | 0.9900 | C15—C16 | 1.397 (3) |
C4—H4B | 0.9900 | C15—H15 | 0.9500 |
C5—C6 | 1.530 (2) | C16—C17 | 1.393 (3) |
C5—H5A | 0.9900 | C16—H16 | 0.9500 |
C5—H5B | 0.9900 | C17—C18 | 1.429 (3) |
C6—C11 | 1.403 (3) | C17—H17 | 0.9500 |
C6—C7 | 1.414 (2) | C18—H18 | 0.9500 |
C7—C8 | 1.406 (3) | ||
C2—O1—H1 | 109.5 | C8—C7—H7 | 119.5 |
C4—O2—H2 | 109.5 | C6—C7—H7 | 119.5 |
C12—N1—C1 | 115.65 (13) | C9—C8—C7 | 119.96 (17) |
C12—N1—C5 | 110.36 (12) | C9—C8—H8 | 120.0 |
C1—N1—C5 | 112.81 (12) | C7—C8—H8 | 120.0 |
N1—C1—C2 | 107.17 (13) | C8—C9—C10 | 119.39 (17) |
N1—C1—C4 | 116.32 (13) | C8—C9—H9 | 120.3 |
C2—C1—C4 | 109.38 (13) | C10—C9—H9 | 120.3 |
N1—C1—H1A | 107.9 | C11—C10—C9 | 120.71 (18) |
C2—C1—H1A | 107.9 | C11—C10—H10 | 119.6 |
C4—C1—H1A | 107.9 | C9—C10—H10 | 119.6 |
O1—C2—C3 | 108.40 (13) | C6—C11—C10 | 120.32 (17) |
O1—C2—C1 | 107.36 (12) | C6—C11—H11 | 119.8 |
C3—C2—C1 | 114.97 (14) | C10—C11—H11 | 119.8 |
O1—C2—H2A | 108.7 | N1—C12—C13 | 114.15 (13) |
C3—C2—H2A | 108.7 | N1—C12—H12A | 108.7 |
C1—C2—H2A | 108.7 | C13—C12—H12A | 108.7 |
C2—C3—H3A | 109.5 | N1—C12—H12B | 108.7 |
C2—C3—H3B | 109.5 | C13—C12—H12B | 108.7 |
H3A—C3—H3B | 109.5 | H12A—C12—H12B | 107.6 |
C2—C3—H3C | 109.5 | C18—C13—C14 | 117.83 (14) |
H3A—C3—H3C | 109.5 | C18—C13—C12 | 120.55 (15) |
H3B—C3—H3C | 109.5 | C14—C13—C12 | 121.61 (16) |
O2—C4—C1 | 112.68 (13) | C13—C14—C15 | 120.95 (18) |
O2—C4—H4A | 109.1 | C13—C14—H14 | 119.5 |
C1—C4—H4A | 109.1 | C15—C14—H14 | 119.5 |
O2—C4—H4B | 109.1 | C16—C15—C14 | 120.55 (19) |
C1—C4—H4B | 109.1 | C16—C15—H15 | 119.7 |
H4A—C4—H4B | 107.8 | C14—C15—H15 | 119.7 |
N1—C5—C6 | 112.13 (13) | C17—C16—C15 | 119.09 (16) |
N1—C5—H5A | 109.2 | C17—C16—H16 | 120.5 |
C6—C5—H5A | 109.2 | C15—C16—H16 | 120.5 |
N1—C5—H5B | 109.2 | C16—C17—C18 | 120.51 (19) |
C6—C5—H5B | 109.2 | C16—C17—H17 | 119.7 |
H5A—C5—H5B | 107.9 | C18—C17—H17 | 119.7 |
C11—C6—C7 | 118.55 (16) | C13—C18—C17 | 121.07 (18) |
C11—C6—C5 | 120.54 (15) | C13—C18—H18 | 119.5 |
C7—C6—C5 | 120.90 (16) | C17—C18—H18 | 119.5 |
C8—C7—C6 | 121.06 (17) |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—HO1···N1 | 0.97 | 2.06 | 2.729 (3) | 125 |
O2—HO2···O1i | 0.97 | 1.87 | 2.789 (2) | 158 |
Symmetry code: (i) x, y+1, z. |
Experimental details
Crystal data | |
Chemical formula | C18H23NO2 |
Mr | 285.37 |
Crystal system, space group | Monoclinic, C2 |
Temperature (K) | 100 |
a, b, c (Å) | 18.6701 (4), 6.652 (1), 16.060 (2) |
β (°) | 123.126 (8) |
V (Å3) | 1670.4 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.07 |
Crystal size (mm) | 0.35 × 0.25 × 0.20 |
Data collection | |
Diffractometer | ? |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 2016, 2016, 1965 |
Rint | 0.000 |
(sin θ/λ)max (Å−1) | 0.648 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.037, 0.091, 1.06 |
No. of reflections | 2016 |
No. of parameters | 193 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.28, −0.16 |
Computer programs: CrysAlis CCD (Oxford Diffraction, 2006), CrysAlis RED (Oxford Diffraction, 2006), SIR92 (Altomare et al., 1993), SHELXL97 (Sheldrick, 1997), SHELXTL (Sheldrick, 1990), publCIF (Westrip, 2007).
D—H···A | D—H | H···A | D···A | D—H···A |
O1—HO1···N1 | 0.967 | 2.061 | 2.729 (3) | 124.58 |
O2—HO2···O1i | 0.967 | 1.868 | 2.789 (2) | 158.19 |
Symmetry code: (i) x, y+1, z. |
Distance/Angle | ELMAN | IAM |
O1–C2 | 1.465 (2) | 1.461 (3) |
O2–C4 | 1.436 (2) | 1.435 (3) |
N1–C1 | 1.502 (2) | 1.502 (3) |
N1–C5 | 1.506 (1) | 1.504 (1) |
N1–C12 | 1.496 (2) | 1.500 (4) |
O1–C2–C1 | 107.3 (2) | 107.3 (4) |
O1–C2–C3 | 108.2 (2) | 108.4 (4) |
O2–C4–C1 | 112.5 (3) | 112.5 (5) |
C1–N1–C5 | 112.6 (3) | 112.8 (5) |
C1–N1–C12 | 115.8 (3) | 115.7 (4) |
C5–N1–C12 | 110.5 (3) | 110.4 (5) |
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Enantiomerically pure amino acids and their derivatives play an important role as indispensable intermediates in the pharmaceutical industry and agrochemistry (Breuer et al., 2004, and references therein). Among these optically active amino-alcohols, L- and/or D-threoninol have received recently much attention as chiral parts of promising drugs against chemokine-mediated diseases (Brough & McInally, 2004), for the synthesis of acridine-DNA conjugates for site-selective RNA scissors (Shi et al., 2005), as linkers for methyl red incorporation into DNA (Kashida, Tanaka et al., 2006), as asymmetric cis-platinum(II) complexes for cancer therapy (van Rijt et al., 2006), as intercalator between pyrene moities and an oligodeoxyribonucleotide for the detection of deletion polymorphisms (Kashida, Asanuma et al., 2006) or between 10–23 DNAzyme and binding arm for RNA cleavage activity enhancement (Asanuma et al., 2006), and for the synthesis of inhibitors of protein kinase C for treatment of inflammation (Peng et al. 2006) or of a small combinatorial library of dihydroceramide analogs (Villorbina et al., 2007).
As part of a programme for the evaluation of new asymmetric catalysts from the chiral pool (Waykole et al., 2007) (ie. amino acids, sugars, etc), we have synthesized the new optically pure α-amino-alcohol (II) in two steps from readily available D-threonine. Diol (II) is a convenient source of D-threoninol by catalytic hydrogenolysis under mild conditions with toluene as sole by-product (Yoshida et al., 1988). We report here the X-ray structure of (II), which was prepared in good yield by reduction of the intermediate ester (I).
The molecular structure of (II) is depicted in Fig. 1. An intramolecular O1—HO1···N1 hydrogen bond (Table 2) forms five-membered ring. Atom N1 is about 0.407 Å out of the plane defined by three neighboring C atoms (C1, C5 and C12) towards hydrogen. The sum of valence angles around the N atom is 338.9°, indicating sp3-hybridization (328° for sp3 and 360° for sp2). The crystal structure of (II) is presented in Fig. 2. Chains along the b axis are formed by O2—HO2···O1i hydrogen bonds [symmetry code: (i) x, y + 1, z; Table 2].
Initially, in the independent atom model (IAM) refinement, a conventional spherical neutral atom model was applied. Scale factors, atomic positions and displacement parameters for all atoms were refined using the MoPro program (Guillot et al., 2001, Jelsch et al., 2005) until convergence. In the experimental library multipolar atom model (ELMAM) refinement, the same parameters were varied but a multipolar charged atom model was applied. The electron-density parameters were transferred from the ELMAM library (Pichon-Pesme et al., 2004; Zarychta et al., 2007) and subsequently kept fixed. Riding restraints on H-atom B factors were applied similarly in both refinements, which were carried out with the same intensity data and cut-off criterion [I/σ(I) ≥ 0]. The H—X distances were restricted to standard values in X-ray and neutron diffraction studies (Allen, 1986) in the IAM and ELMAM refinements, respectively (0.002 Å distance σ). The ELMAM refinement shows a good improvement in statistical indexes when compared with the IAM refinement; the R(F) factor is reduced from 4.22 to 3.02%, and wR(R) from 5.12 to 3.37%. The minimum and maximum peaks in the residual electron density are -0.036 and +0.056 e Å-3 after the IAM refinement and -0.028 and +0.039 e Å-3 after the ELMAN refinement. The most significant differences in the geometry of compound (II) are, as expected, the bond distances involving H atoms, which had different targets in the ELMAN and IAM refinements. When H atoms are not considered, the r.m.s. deviation between the two structures is 0.0067 Å, while the r.m.s. discrepancy for the bond lengths is 0.0055 Å. The differences do not exceed 0.015 Å for bond distances and 0.5° for bond angles when H atoms are excluded. The H—C—H angles show the strongest (2.9°) r.m.s. discrepancy, the X—Y—H angles differ by 1.8°, while the X—Y—Z angles are less affected with a low (0.2°) r.m.s. difference. The s.u. values of the bond distances and angles are smaller with the ELMAM owing to better R-factor values (Table 1).
The largest effect of the multipoles transfer on the crystallographic structure is observed in the atomic thermal motion. The r.m.s. difference over all the Uij parameters reaches 16% between the two refinement models. The Uij values derived from the IAM refinement have an r.m.s. value 10% larger on average than those derived from the ELMAM refinement. With the IAM spherical atom model, the displacement parameters are incorrect as they incorporate some significant deformation electron density, due to improper deconvolution between these two features (Jelsch et al., 1998).