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Benzyl N-[(S)-2-hydroxy-1-({[(E)-2-hydroxy-4-methoxybenzylidene]hydrazinyl}carbonyl)ethyl]carbamate
aFundação Oswaldo Cruz, Instituto de Tecnologia, em Fármacos – Farmanguinhos, R. Sizenando Nabuco, 100, Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil, bDepartment of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia, cCHEMSOL, 1 Harcourt Road, Aberdeen AB15 5NY, Scotland, and dCentro de Desenvolvimento Tecnológico em Saúde (CDTS), Fundação Oswaldo Cruz (FIOCRUZ), Casa Amarela, Campus de Manguinhos, Av. Brasil 4365, 21040-900 Rio de Janeiro, RJ, Brazil
*Correspondence e-mail: edward.tiekink@gmail.com
The shape of the title compound, C19H21N3O6, is curved with the conformation about the imine bond [1.291 (3) Å] being E. While the hydroxy-substituted benzene ring is almost coplanar with the hydrazinyl residue [N—N—C—C = 177.31 (18)°], an observation correlated with an intramolecular O—H⋯N hydrogen bond leading to an S(6) ring, the remaining residues exhibit significant twists. The carbonyl residues are directed away from each other as are the This allows for the formation of O—H⋯O and N—H⋯O hydrogen bonds in the crystal, which lead to two-dimensional supramolecular arrays in the ac plane. Additional stabilization to the layers is afforded by C—H⋯π interactions.
Related literature
For the use of L-serine derivatives in anti-tumour therapy, see: Jiao et al. (2009); Yakura et al. (2007
); Takahashi et al. (1988
); Sin et al. (1998
). For the use of N-acylhydrazones derivatives from L-serine in anti-tumour testing, see: Rollas & Küçükgüzel (2007
); Terzioğlu & Gürsoy (2003
). For a related structure, see: Pinheiro et al. (2010
).
Experimental
Crystal data
|
Refinement
|
|
Data collection: COLLECT (Hooft, 1998); cell DENZO (Otwinowski & Minor, 1997
) and COLLECT; data reduction: DENZO and COLLECT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008
); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008
); molecular graphics: ORTEP-3 (Farrugia, 1997
) and DIAMOND (Brandenburg, 2006
); software used to prepare material for publication: publCIF (Westrip, 2010
).
Supporting information
https://doi.org/10.1107/S1600536810047720/hb5744sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810047720/hb5744Isup2.hkl
The compound, phenyl (1S)-2-hydrazino-1-(hydroxymethyl)-2-oxoethylcarbamate, was obtained from L-serine methyl ester hydrochloride on successive reactions with (a) PhCH2Cl and Et3N, and (b) N2H4.H2O. To a stirred ethanol solution (10 ml) of phenyl (1S)-2-hydrazino-1-(hydroxymethyl)-2-oxoethylcarbamate (1.0 mmol) at room temperature was added 2-hydroxy-4-methoxybenzaldehyde (1.05 mmol). The reaction mixture was stirred for 4 h at 353 K and concentrated under reduced pressure. The residue was purified by washing with cold ethanol (3 x 10 ml), affording (I), yield 80%; m.p. 435 K. The NMR spectra in DMSO solution revealed the presence of (E)- and (Z)-isomers. However, the colourless needles obtained from methanol were solely the (E)-isomer.
1H NMR (500 MHz, DMSO-d6) δ (p.p.m.): 11.68 & 11.27 (1H, s, NHN, E & Z isomers), 10.45 & 10.17 (1H, s C1—OH, E & Z isomers), 8.36 & 8.19 (1H, s, N═CH, E & Z isomers), 7.60 (d, J = 8.8 Hz) & 7.47 (d, J = 7.8 Hz), (1H, H5, E & Z isomers), 7.40 (d, J = 8.4 Hz) & 7.38–7.25 (m), (1H, NHCH, E & Z isomers), 7.38–7.25 (5H, m, Ph), 6.55–6.40 (2H, m, H2 & H4), 5.04 (2H, s, CH2Ph), 5.10–5.00 (m) & 4.89 (t, J = 5.9 Hz), (1H, OH, E & Z isomers), 4.93 &.5.11 (1H, m, CH, E & Z isomers), 3,76 & 3.74 (3H, s, CH3, E & Z isomers), 3.70–3.55 (2H, m, CH2OH). 13C NMR (125 MHz, DMSO-d6) δ (p.p.m.): 171.2 & 167.0 (COCH, E & Z isomers), 162.5 & 162.2 (C3, E & Z isomers), 159.7 & 158.3 (C1, E & Z isomers) 156.4 (COO), 148.4 & 141.7 (N═CH, E & Z isomers), 137.4 (C6') 131.5, 128.8, 128.7, 128.3, 128.2 & 127.6 (C5, C1', C2', C3', C4' & C5'), 112.1 (C6), 106.9 (C4), 101.6 (C2), 66.0 & 65.8 (CH2Ph, E & Z isomers), 61.9 & 61.5 (CH2OH, E & Z isomers), 56.7 & 54.9 (CH, E & Z isomers), 55.8 & 55.6 (CH3; E & Z isomers). IR (cm-1; KBr): 3329 (O—H), 1678 (CO). EM/ESI: [M—H]: 386.3.
The C-bound H atoms were geometrically placed (C–H = 0.95–0.99 Å) and refined as riding with Uiso(H) = 1.2–1.5Ueq(C). The O– and N-bound H atoms were located from a difference map and refined with the distance restraint O–H = 0.84 ± 0.01 and N–H = 0.86±0.01 Å, and with Uiso(H) = zUeq(carrier atom); z = 1.5 for O and z = 1.2 for N. In the absence of significant
effects, 1934 Friedel pairs were averaged in the final However, the was assigned on the basis of the of the L-serine starting material. In the final two reflections exhibiting poor agreement were omitted, i.e. (001) and (011).Several L-serine derivatives have been found to have potential in anti-tumour therapy, for example, conagenin, a naturally occurring serine derivative, was shown to improve the anti-tumour efficacy of adriamycin and mitomycin C against murine leukemias (Jiao et al., 2009; Yakura et al., 2007). Other L-serine derivatives reported as potential new anti-tumour agents include the anti-biotic thrazarine, which sensitizes tumour cells to macrophage-mediated cytolysis (Takahashi et al., 1988), and eponemycin, an immunomodulator, which plays a crucial role in tumour progression and metastases by supplying essential nutrients to B16 melanoma cells (Sin et al., 1998).
Following on from such reports, we have synthesized some N-acylhydrazones derivatives from L-serine to use in anti-tumour testing. The choice of N-acylhydrazonyl derivatives was suggested by publications indicating that compounds with such groups can aid anti-tumour activities (Rollas & Küçükgüzel, 2007; Terzioğlu & Gürsoy, 2003). We recently reported the structure of benzyl (1S)-2-[2-(2-methoxybenzylidene)hydrazino]-1-(hydroxymethyl)-2-oxoethylcarbamate (Pinheiro et al., 2010) and now we wish to report the structure of the 2-hydroxy-4-methoxy analogue, (I).
Although the ═C8 bond [1.291 (3) Å] is E. The observed planar conformation is stabilized by an intramolecular O1—H···N1 bond that closes an S(6) ring, Table 1. A noticeable twist is evident about the hydrazino bond [C8—N1—N2—C9 = -167.97 (19) °], and the remainder of the molecule is similarly twisted. The twists in the molecule results in a conformation where the two carbonyl atoms are directed away from each other, and a similar situation pertains for the amine groups. This arrangement optimizes the formation of a number of strong hydrogen bonds.
of (I), Fig. 1, could not be determined experimentally, the assignment of the S-configuration at the C10 atom is based on a starting reagent. Overall, the molecule of (I) is curved. The 2-hydroxy-4-methoxyphenyl group is planar [the C7—O2—C4—C3 torsion angle is -1.2 (3) °] and the planarity extends to include the hydrazino residue [N2—N1—C8—C1 = 177.31 (18) °]; the conformation about the N1In the crystal packing, the O4-hydroxyl group forms an O—H···O hydrogen bond with the carbonyl-O3 atom adjacent to the hydrazino residue, Table 1. Each of the N—H atoms form a N—H···O hydrogen bond: N2 to the O4-hydroxyl group and N3 to the O5-ester atom, Table 1. This results in the formation of supramolecular layers in the ac plane, Fig. 2. Additional stabilization to the layers is afforded by C—H···π interactions, Table 1 and Fig. 2.
For the use of L-serine derivatives in anti-tumour therapy, see: Jiao et al. (2009); Yakura et al. (2007); Takahashi et al. (1988); Sin et al. (1998). For the use of N-acylhydrazones derivatives from L-serine in anti-tumour testing, see: Rollas & Küçükgüzel (2007); Terzioğlu & Gürsoy (2003). For a related structure, see: Pinheiro et al. (2010).
Data collection: COLLECT (Hooft, 1998); cell
DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1998); data reduction: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997) and DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010).C19H21N3O6 | F(000) = 408 |
Mr = 387.39 | Dx = 1.393 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 9310 reflections |
a = 5.1634 (2) Å | θ = 2.9–27.5° |
b = 32.3173 (11) Å | µ = 0.11 mm−1 |
c = 5.7030 (2) Å | T = 120 K |
β = 103.918 (2)° | Prism, colourless |
V = 923.70 (6) Å3 | 0.50 × 0.32 × 0.10 mm |
Z = 2 |
Bruker–Nonius Roper CCD camera on κ-goniostat diffractometer | 2151 independent reflections |
Radiation source: Bruker-Nonius FR591 rotating anode | 1954 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.035 |
Detector resolution: 9.091 pixels mm-1 | θmax = 27.5°, θmin = 3.7° |
φ and ω scans | h = −6→6 |
Absorption correction: multi-scan (SADABS; Sheldrick, 2007) | k = −41→41 |
Tmin = 0.623, Tmax = 0.746 | l = −7→7 |
9676 measured reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.032 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.078 | w = 1/[σ2(Fo2) + (0.0441P)2 + 0.1213P] where P = (Fo2 + 2Fc2)/3 |
S = 1.01 | (Δ/σ)max = 0.001 |
2149 reflections | Δρmax = 0.14 e Å−3 |
266 parameters | Δρmin = −0.19 e Å−3 |
5 restraints | Absolute structure: nd |
Primary atom site location: structure-invariant direct methods |
C19H21N3O6 | V = 923.70 (6) Å3 |
Mr = 387.39 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 5.1634 (2) Å | µ = 0.11 mm−1 |
b = 32.3173 (11) Å | T = 120 K |
c = 5.7030 (2) Å | 0.50 × 0.32 × 0.10 mm |
β = 103.918 (2)° |
Bruker–Nonius Roper CCD camera on κ-goniostat diffractometer | 2151 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2007) | 1954 reflections with I > 2σ(I) |
Tmin = 0.623, Tmax = 0.746 | Rint = 0.035 |
9676 measured reflections |
R[F2 > 2σ(F2)] = 0.032 | 5 restraints |
wR(F2) = 0.078 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.01 | Δρmax = 0.14 e Å−3 |
2149 reflections | Δρmin = −0.19 e Å−3 |
266 parameters | Absolute structure: nd |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | −0.1786 (3) | 1.07693 (5) | 0.1104 (3) | 0.0267 (3) | |
H1O | −0.050 (4) | 1.0606 (8) | 0.111 (5) | 0.040* | |
O2 | −0.3856 (3) | 1.18463 (5) | 0.6089 (3) | 0.0345 (4) | |
O3 | 0.3291 (3) | 0.99440 (5) | −0.1161 (3) | 0.0296 (4) | |
O4 | 0.8158 (3) | 0.98932 (5) | −0.2785 (3) | 0.0292 (3) | |
H4O | 0.981 (2) | 0.9933 (11) | −0.240 (5) | 0.044* | |
O5 | 1.1738 (3) | 0.91538 (5) | 0.3209 (3) | 0.0280 (3) | |
O6 | 0.9066 (3) | 0.87370 (4) | 0.4806 (3) | 0.0232 (3) | |
N1 | 0.2721 (4) | 1.03527 (5) | 0.2864 (3) | 0.0229 (4) | |
N2 | 0.4763 (3) | 1.00743 (5) | 0.2848 (3) | 0.0225 (4) | |
H2N | 0.597 (4) | 1.0034 (8) | 0.415 (3) | 0.027* | |
N3 | 0.7233 (3) | 0.92467 (5) | 0.2328 (3) | 0.0214 (4) | |
H3N | 0.575 (3) | 0.9171 (8) | 0.263 (4) | 0.026* | |
C1 | 0.1100 (4) | 1.08823 (6) | 0.5067 (4) | 0.0234 (4) | |
C2 | −0.1163 (4) | 1.09787 (7) | 0.3212 (4) | 0.0225 (4) | |
C3 | −0.2859 (4) | 1.13016 (7) | 0.3504 (4) | 0.0251 (4) | |
H3 | −0.4368 | 1.1368 | 0.2240 | 0.030* | |
C4 | −0.2330 (5) | 1.15243 (6) | 0.5648 (4) | 0.0267 (5) | |
C5 | −0.0123 (5) | 1.14263 (8) | 0.7516 (4) | 0.0310 (5) | |
H5 | 0.0222 | 1.1578 | 0.8987 | 0.037* | |
C6 | 0.1537 (5) | 1.11119 (7) | 0.7217 (4) | 0.0291 (5) | |
H6 | 0.3029 | 1.1047 | 0.8500 | 0.035* | |
C7 | −0.6104 (5) | 1.19656 (7) | 0.4213 (5) | 0.0332 (5) | |
H7A | −0.5516 | 1.2027 | 0.2740 | 0.050* | |
H7B | −0.6934 | 1.2212 | 0.4717 | 0.050* | |
H7C | −0.7403 | 1.1739 | 0.3896 | 0.050* | |
C8 | 0.3021 (4) | 1.05654 (7) | 0.4826 (4) | 0.0243 (4) | |
H8 | 0.4518 | 1.0514 | 0.6132 | 0.029* | |
C9 | 0.4915 (4) | 0.98936 (6) | 0.0787 (4) | 0.0205 (4) | |
C10 | 0.7381 (4) | 0.96234 (6) | 0.0944 (4) | 0.0194 (4) | |
H10 | 0.8987 | 0.9784 | 0.1799 | 0.023* | |
C11 | 0.7671 (4) | 0.95243 (7) | −0.1585 (4) | 0.0243 (4) | |
H11A | 0.9168 | 0.9329 | −0.1487 | 0.029* | |
H11B | 0.6019 | 0.9390 | −0.2521 | 0.029* | |
C12 | 0.9530 (4) | 0.90556 (6) | 0.3433 (4) | 0.0215 (4) | |
C13 | 1.1447 (4) | 0.85176 (7) | 0.6038 (4) | 0.0309 (5) | |
H13A | 1.2736 | 0.8713 | 0.7031 | 0.037* | |
H13B | 1.2301 | 0.8387 | 0.4844 | 0.037* | |
C14 | 1.0676 (4) | 0.81910 (7) | 0.7625 (4) | 0.0269 (5) | |
C15 | 1.1859 (5) | 0.78017 (7) | 0.7770 (5) | 0.0355 (6) | |
H15 | 1.3004 | 0.7736 | 0.6746 | 0.043* | |
C16 | 1.1382 (5) | 0.75094 (8) | 0.9394 (5) | 0.0394 (6) | |
H16 | 1.2225 | 0.7247 | 0.9493 | 0.047* | |
C17 | 0.9694 (5) | 0.75974 (8) | 1.0862 (4) | 0.0347 (5) | |
H17 | 0.9395 | 0.7398 | 1.1991 | 0.042* | |
C18 | 0.8429 (5) | 0.79800 (8) | 1.0684 (4) | 0.0358 (6) | |
H18 | 0.7217 | 0.8039 | 1.1656 | 0.043* | |
C19 | 0.8938 (5) | 0.82745 (7) | 0.9084 (4) | 0.0315 (5) | |
H19 | 0.8087 | 0.8537 | 0.8984 | 0.038* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0242 (8) | 0.0238 (8) | 0.0305 (8) | 0.0034 (6) | 0.0034 (6) | −0.0037 (6) |
O2 | 0.0306 (9) | 0.0285 (8) | 0.0460 (10) | 0.0027 (7) | 0.0122 (7) | −0.0117 (7) |
O3 | 0.0182 (7) | 0.0414 (9) | 0.0264 (8) | 0.0038 (7) | −0.0003 (6) | 0.0081 (7) |
O4 | 0.0185 (7) | 0.0398 (9) | 0.0280 (7) | −0.0006 (7) | 0.0031 (6) | 0.0156 (7) |
O5 | 0.0189 (7) | 0.0290 (8) | 0.0369 (8) | 0.0027 (6) | 0.0084 (6) | 0.0102 (7) |
O6 | 0.0179 (7) | 0.0238 (7) | 0.0278 (8) | 0.0034 (6) | 0.0052 (6) | 0.0083 (6) |
N1 | 0.0204 (9) | 0.0178 (9) | 0.0309 (9) | 0.0042 (7) | 0.0070 (7) | 0.0049 (7) |
N2 | 0.0186 (8) | 0.0203 (8) | 0.0268 (9) | 0.0048 (7) | 0.0022 (7) | 0.0048 (7) |
N3 | 0.0163 (8) | 0.0220 (9) | 0.0263 (9) | 0.0011 (6) | 0.0062 (7) | 0.0071 (7) |
C1 | 0.0250 (11) | 0.0201 (10) | 0.0265 (11) | −0.0013 (8) | 0.0088 (8) | 0.0037 (8) |
C2 | 0.0219 (10) | 0.0199 (10) | 0.0278 (11) | −0.0037 (8) | 0.0098 (8) | 0.0005 (8) |
C3 | 0.0196 (10) | 0.0229 (10) | 0.0332 (11) | −0.0014 (8) | 0.0071 (8) | −0.0020 (9) |
C4 | 0.0281 (11) | 0.0193 (10) | 0.0368 (13) | −0.0021 (8) | 0.0162 (9) | −0.0020 (9) |
C5 | 0.0379 (13) | 0.0275 (12) | 0.0288 (11) | −0.0028 (10) | 0.0102 (10) | −0.0021 (9) |
C6 | 0.0336 (12) | 0.0276 (11) | 0.0248 (11) | 0.0013 (10) | 0.0043 (9) | 0.0028 (9) |
C7 | 0.0298 (12) | 0.0246 (11) | 0.0480 (14) | 0.0019 (9) | 0.0147 (10) | −0.0025 (11) |
C8 | 0.0245 (10) | 0.0204 (10) | 0.0283 (11) | 0.0000 (8) | 0.0069 (8) | 0.0054 (9) |
C9 | 0.0165 (9) | 0.0198 (10) | 0.0244 (10) | −0.0010 (8) | 0.0036 (7) | 0.0049 (8) |
C10 | 0.0154 (9) | 0.0210 (10) | 0.0207 (9) | −0.0016 (8) | 0.0020 (7) | 0.0046 (8) |
C11 | 0.0245 (11) | 0.0261 (11) | 0.0225 (10) | 0.0002 (8) | 0.0059 (8) | 0.0040 (9) |
C12 | 0.0213 (10) | 0.0213 (10) | 0.0224 (9) | 0.0024 (8) | 0.0065 (8) | 0.0027 (8) |
C13 | 0.0222 (11) | 0.0295 (12) | 0.0396 (13) | 0.0071 (9) | 0.0047 (9) | 0.0159 (11) |
C14 | 0.0243 (11) | 0.0252 (11) | 0.0286 (11) | −0.0002 (8) | 0.0010 (9) | 0.0058 (9) |
C15 | 0.0369 (14) | 0.0303 (12) | 0.0428 (14) | 0.0085 (10) | 0.0166 (11) | 0.0103 (11) |
C16 | 0.0460 (15) | 0.0262 (12) | 0.0500 (15) | 0.0085 (11) | 0.0192 (12) | 0.0128 (11) |
C17 | 0.0452 (15) | 0.0279 (12) | 0.0314 (12) | −0.0017 (10) | 0.0099 (10) | 0.0071 (10) |
C18 | 0.0459 (15) | 0.0346 (13) | 0.0306 (12) | 0.0000 (11) | 0.0167 (11) | 0.0017 (10) |
C19 | 0.0368 (13) | 0.0239 (12) | 0.0344 (13) | 0.0038 (9) | 0.0098 (10) | 0.0028 (10) |
O1—C2 | 1.349 (3) | C5—H5 | 0.9500 |
O1—H1O | 0.846 (10) | C6—H6 | 0.9500 |
O2—C4 | 1.365 (3) | C7—H7A | 0.9800 |
O2—C7 | 1.430 (3) | C7—H7B | 0.9800 |
O3—C9 | 1.231 (2) | C7—H7C | 0.9800 |
O4—C11 | 1.427 (3) | C8—H8 | 0.9500 |
O4—H4O | 0.840 (10) | C9—C10 | 1.529 (3) |
O5—C12 | 1.219 (3) | C10—C11 | 1.519 (3) |
O6—C12 | 1.349 (2) | C10—H10 | 1.0000 |
O6—C13 | 1.446 (2) | C11—H11A | 0.9900 |
N1—C8 | 1.291 (3) | C11—H11B | 0.9900 |
N1—N2 | 1.388 (2) | C13—C14 | 1.505 (3) |
N2—C9 | 1.332 (3) | C13—H13A | 0.9900 |
N2—H2N | 0.857 (10) | C13—H13B | 0.9900 |
N3—C12 | 1.351 (3) | C14—C19 | 1.389 (3) |
N3—C10 | 1.463 (3) | C14—C15 | 1.393 (3) |
N3—H3N | 0.861 (10) | C15—C16 | 1.385 (4) |
C1—C6 | 1.404 (3) | C15—H15 | 0.9500 |
C1—C2 | 1.410 (3) | C16—C17 | 1.376 (4) |
C1—C8 | 1.455 (3) | C16—H16 | 0.9500 |
C2—C3 | 1.398 (3) | C17—C18 | 1.391 (4) |
C3—C4 | 1.388 (3) | C17—H17 | 0.9500 |
C3—H3 | 0.9500 | C18—C19 | 1.387 (3) |
C4—C5 | 1.396 (3) | C18—H18 | 0.9500 |
C5—C6 | 1.366 (3) | C19—H19 | 0.9500 |
C2—O1—H1O | 107 (2) | N2—C9—C10 | 115.08 (16) |
C4—O2—C7 | 117.93 (18) | N3—C10—C11 | 111.51 (16) |
C11—O4—H4O | 107 (2) | N3—C10—C9 | 110.83 (16) |
C12—O6—C13 | 114.04 (16) | C11—C10—C9 | 109.62 (16) |
C8—N1—N2 | 114.69 (18) | N3—C10—H10 | 108.3 |
C9—N2—N1 | 119.74 (17) | C11—C10—H10 | 108.3 |
C9—N2—H2N | 120.9 (19) | C9—C10—H10 | 108.3 |
N1—N2—H2N | 119.3 (18) | O4—C11—C10 | 110.37 (17) |
C12—N3—C10 | 118.55 (17) | O4—C11—H11A | 109.6 |
C12—N3—H3N | 120.1 (17) | C10—C11—H11A | 109.6 |
C10—N3—H3N | 120.6 (18) | O4—C11—H11B | 109.6 |
C6—C1—C2 | 117.9 (2) | C10—C11—H11B | 109.6 |
C6—C1—C8 | 119.0 (2) | H11A—C11—H11B | 108.1 |
C2—C1—C8 | 123.06 (19) | O5—C12—O6 | 124.06 (19) |
O1—C2—C3 | 117.29 (19) | O5—C12—N3 | 124.77 (19) |
O1—C2—C1 | 122.32 (19) | O6—C12—N3 | 111.17 (17) |
C3—C2—C1 | 120.38 (19) | O6—C13—C14 | 108.60 (18) |
C4—C3—C2 | 119.7 (2) | O6—C13—H13A | 110.0 |
C4—C3—H3 | 120.2 | C14—C13—H13A | 110.0 |
C2—C3—H3 | 120.2 | O6—C13—H13B | 110.0 |
O2—C4—C3 | 123.9 (2) | C14—C13—H13B | 110.0 |
O2—C4—C5 | 115.7 (2) | H13A—C13—H13B | 108.4 |
C3—C4—C5 | 120.4 (2) | C19—C14—C15 | 118.5 (2) |
C6—C5—C4 | 119.6 (2) | C19—C14—C13 | 121.8 (2) |
C6—C5—H5 | 120.2 | C15—C14—C13 | 119.6 (2) |
C4—C5—H5 | 120.2 | C16—C15—C14 | 120.6 (2) |
C5—C6—C1 | 121.9 (2) | C16—C15—H15 | 119.7 |
C5—C6—H6 | 119.1 | C14—C15—H15 | 119.7 |
C1—C6—H6 | 119.1 | C17—C16—C15 | 120.4 (2) |
O2—C7—H7A | 109.5 | C17—C16—H16 | 119.8 |
O2—C7—H7B | 109.5 | C15—C16—H16 | 119.8 |
H7A—C7—H7B | 109.5 | C16—C17—C18 | 119.7 (2) |
O2—C7—H7C | 109.5 | C16—C17—H17 | 120.2 |
H7A—C7—H7C | 109.5 | C18—C17—H17 | 120.2 |
H7B—C7—H7C | 109.5 | C19—C18—C17 | 119.9 (2) |
N1—C8—C1 | 120.96 (19) | C19—C18—H18 | 120.1 |
N1—C8—H8 | 119.5 | C17—C18—H18 | 120.1 |
C1—C8—H8 | 119.5 | C18—C19—C14 | 120.9 (2) |
O3—C9—N2 | 124.50 (19) | C18—C19—H19 | 119.6 |
O3—C9—C10 | 120.36 (19) | C14—C19—H19 | 119.6 |
C8—N1—N2—C9 | −167.97 (19) | C12—N3—C10—C9 | −154.94 (18) |
C6—C1—C2—O1 | −178.4 (2) | O3—C9—C10—N3 | −112.2 (2) |
C8—C1—C2—O1 | 3.3 (3) | N2—C9—C10—N3 | 70.4 (2) |
C6—C1—C2—C3 | 1.8 (3) | O3—C9—C10—C11 | 11.3 (3) |
C8—C1—C2—C3 | −176.6 (2) | N2—C9—C10—C11 | −166.09 (17) |
O1—C2—C3—C4 | 179.26 (19) | N3—C10—C11—O4 | −172.47 (16) |
C1—C2—C3—C4 | −0.9 (3) | C9—C10—C11—O4 | 64.4 (2) |
C7—O2—C4—C3 | −1.2 (3) | C13—O6—C12—O5 | 0.5 (3) |
C7—O2—C4—C5 | 178.6 (2) | C13—O6—C12—N3 | 179.84 (18) |
C2—C3—C4—O2 | 179.4 (2) | C10—N3—C12—O5 | −6.3 (3) |
C2—C3—C4—C5 | −0.3 (3) | C10—N3—C12—O6 | 174.38 (16) |
O2—C4—C5—C6 | −179.1 (2) | C12—O6—C13—C14 | 176.21 (18) |
C3—C4—C5—C6 | 0.7 (3) | O6—C13—C14—C19 | −45.1 (3) |
C4—C5—C6—C1 | 0.3 (4) | O6—C13—C14—C15 | 139.2 (2) |
C2—C1—C6—C5 | −1.5 (3) | C19—C14—C15—C16 | −2.2 (4) |
C8—C1—C6—C5 | 176.9 (2) | C13—C14—C15—C16 | 173.6 (2) |
N2—N1—C8—C1 | 177.31 (18) | C14—C15—C16—C17 | 1.1 (4) |
C6—C1—C8—N1 | −178.7 (2) | C15—C16—C17—C18 | 1.0 (4) |
C2—C1—C8—N1 | −0.4 (3) | C16—C17—C18—C19 | −2.0 (4) |
N1—N2—C9—O3 | −2.6 (3) | C17—C18—C19—C14 | 0.8 (4) |
N1—N2—C9—C10 | 174.73 (17) | C15—C14—C19—C18 | 1.2 (4) |
C12—N3—C10—C11 | 82.6 (2) | C13—C14—C19—C18 | −174.5 (2) |
Cg1 is the centroid of the C1–C6 ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1o···N1 | 0.85 (2) | 1.91 (2) | 2.667 (3) | 149 (3) |
N2—H2n···O4i | 0.86 (2) | 1.89 (2) | 2.742 (2) | 170 (2) |
N3—H3n···O5ii | 0.86 (2) | 2.18 (2) | 3.013 (2) | 165 (2) |
O4—H4o···O3iii | 0.84 (2) | 1.77 (2) | 2.594 (2) | 169 (3) |
C7—H7c···Cg1ii | 0.98 | 2.67 | 3.565 (3) | 151 |
Symmetry codes: (i) x, y, z+1; (ii) x−1, y, z; (iii) x+1, y, z. |
Experimental details
Crystal data | |
Chemical formula | C19H21N3O6 |
Mr | 387.39 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 120 |
a, b, c (Å) | 5.1634 (2), 32.3173 (11), 5.7030 (2) |
β (°) | 103.918 (2) |
V (Å3) | 923.70 (6) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.50 × 0.32 × 0.10 |
Data collection | |
Diffractometer | Bruker–Nonius Roper CCD camera on κ-goniostat |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2007) |
Tmin, Tmax | 0.623, 0.746 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 9676, 2151, 1954 |
Rint | 0.035 |
(sin θ/λ)max (Å−1) | 0.650 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.032, 0.078, 1.01 |
No. of reflections | 2149 |
No. of parameters | 266 |
No. of restraints | 5 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.14, −0.19 |
Absolute structure | Nd |
Computer programs: DENZO (Otwinowski & Minor, 1997) and COLLECT (Hooft, 1998), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997) and DIAMOND (Brandenburg, 2006), publCIF (Westrip, 2010).
Cg1 is the centroid of the C1–C6 ring. |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1o···N1 | 0.85 (2) | 1.91 (2) | 2.667 (3) | 149 (3) |
N2—H2n···O4i | 0.857 (18) | 1.894 (18) | 2.742 (2) | 170 (2) |
N3—H3n···O5ii | 0.860 (18) | 2.175 (17) | 3.013 (2) | 165 (2) |
O4—H4o···O3iii | 0.838 (15) | 1.766 (16) | 2.594 (2) | 169 (3) |
C7—H7c···Cg1ii | 0.98 | 2.67 | 3.565 (3) | 151 |
Symmetry codes: (i) x, y, z+1; (ii) x−1, y, z; (iii) x+1, y, z. |
Footnotes
‡Additional correspondence author, e-mail: j.wardell@abdn.ac.uk.
Acknowledgements
The use of the EPSRC X-ray crystallographic service at the University of Southampton, England, and the valuable assistance of the staff there is gratefully acknowledged. JLW acknowledges support from CAPES (Brazil).
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Several L-serine derivatives have been found to have potential in anti-tumour therapy, for example, conagenin, a naturally occurring serine derivative, was shown to improve the anti-tumour efficacy of adriamycin and mitomycin C against murine leukemias (Jiao et al., 2009; Yakura et al., 2007). Other L-serine derivatives reported as potential new anti-tumour agents include the anti-biotic thrazarine, which sensitizes tumour cells to macrophage-mediated cytolysis (Takahashi et al., 1988), and eponemycin, an immunomodulator, which plays a crucial role in tumour progression and metastases by supplying essential nutrients to B16 melanoma cells (Sin et al., 1998).
Following on from such reports, we have synthesized some N-acylhydrazones derivatives from L-serine to use in anti-tumour testing. The choice of N-acylhydrazonyl derivatives was suggested by publications indicating that compounds with such groups can aid anti-tumour activities (Rollas & Küçükgüzel, 2007; Terzioğlu & Gürsoy, 2003). We recently reported the structure of benzyl (1S)-2-[2-(2-methoxybenzylidene)hydrazino]-1-(hydroxymethyl)-2-oxoethylcarbamate (Pinheiro et al., 2010) and now we wish to report the structure of the 2-hydroxy-4-methoxy analogue, (I).
Although the absolute structure of (I), Fig. 1, could not be determined experimentally, the assignment of the S-configuration at the C10 atom is based on a starting reagent. Overall, the molecule of (I) is curved. The 2-hydroxy-4-methoxyphenyl group is planar [the C7—O2—C4—C3 torsion angle is -1.2 (3) °] and the planarity extends to include the hydrazino residue [N2—N1—C8—C1 = 177.31 (18) °]; the conformation about the N1═C8 bond [1.291 (3) Å] is E. The observed planar conformation is stabilized by an intramolecular O1—H···N1 bond that closes an S(6) ring, Table 1. A noticeable twist is evident about the hydrazino bond [C8—N1—N2—C9 = -167.97 (19) °], and the remainder of the molecule is similarly twisted. The twists in the molecule results in a conformation where the two carbonyl atoms are directed away from each other, and a similar situation pertains for the amine groups. This arrangement optimizes the formation of a number of strong hydrogen bonds.
In the crystal packing, the O4-hydroxyl group forms an O—H···O hydrogen bond with the carbonyl-O3 atom adjacent to the hydrazino residue, Table 1. Each of the N—H atoms form a N—H···O hydrogen bond: N2 to the O4-hydroxyl group and N3 to the O5-ester atom, Table 1. This results in the formation of supramolecular layers in the ac plane, Fig. 2. Additional stabilization to the layers is afforded by C—H···π interactions, Table 1 and Fig. 2.