Benzyl N-(2-hy­droxy-1-{N′-[(1E)-2-hy­droxy­benzyl­idene]hydrazinecarbon­yl}eth­yl)carbamate

Edward R T Tiekink; Marcus V N de Souza; Alessandra C Pinheiro; Solange M S V Wardell; James L Wardell

doi:10.1107/S1600536811025128

. 2011 Jun 30;67(Pt 7):o1866–o1867. doi: 10.1107/S1600536811025128

Benzyl N-(2-hydroxy-1-{N′-[(1E)-2-hydroxybenzylidene]hydrazinecarbonyl}ethyl)carbamate

Edward R T Tiekink ^a,^*, Marcus V N de Souza ^b, Alessandra C Pinheiro ^b, Solange M S V Wardell ^c, James L Wardell ^d,^‡

PMCID: PMC3151747 PMID: 21837230

Abstract

The molecule of the title compound, C₁₈H₁₉N₃O₅, adopts a curved arrangement with the terminal benzene rings lying to the same side. The hydroxylbenzene ring is close to coplanar with the adjacent hydrazine residue [dihedral angle = 11.14 (12)°], an observation which correlates with the presence of an intramolecular O—H⋯N hydrogen bond. The benzyl ring forms a dihedral angle of 50.84 (13)° with the adjacent carbamate group. A twist in the molecule, at the chiral C atom, is reflected in the dihedral angle of 80.21 (12)° formed between the amide residues. In the crystal, two-dimensional arrays in the ac plane are mediated by O—H⋯O and N—H⋯O hydrogen bonds.

Related literature

For background to the use of l-serine derivatives in anti-tumour therapy, see: Jiao et al. (2009 ▶); Yakura et al. (2007 ▶). For background to N-acylhydrazone derivatives from l-serine for anti-tumour testing, see: Pinheiro et al. (2010 ▶, 2011a ▶,b ▶); de Souza et al. (2010 ▶, 2011 ▶); Howie et al. (2011 ▶).

Experimental

Crystal data

C₁₈H₁₉N₃O₅
M _r = 357.36
Monoclinic,
a = 5.0338 (5) Å
b = 31.357 (3) Å
c = 5.5882 (6) Å
β = 97.890 (3)°
V = 873.72 (16) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 120 K
0.25 × 0.05 × 0.02 mm

Data collection

Bruker–Nonius Roper CCD camera on κ-goniostat diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2007 ▶) T _min = 0.654, T _max = 0.746
8786 measured reflections
2034 independent reflections
1485 reflections with I > 2σ(I)
R _int = 0.066

Refinement

R[F ² > 2σ(F ²)] = 0.053
wR(F ²) = 0.098
S = 1.06
2034 reflections
247 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.20 e Å⁻³

Data collection: COLLECT (Hooft, 1998 ▶); cell refinement: 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 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811025128/hb5935sup1.cif

e-67-o1866-sup1.cif^{(20.2KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811025128/hb5935Isup2.hkl

e-67-o1866-Isup2.hkl^{(98KB, hkl)}

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1o⋯N1	0.90 (5)	1.88 (5)	2.648 (4)	143 (4)
O3—H3o⋯O2ⁱ	0.84 (5)	1.79 (5)	2.616 (4)	167 (5)
N2—H2n⋯O3ⁱⁱ	0.90 (4)	1.87 (4)	2.758 (4)	168 (4)
N3—H3n⋯O4ⁱⁱⁱ	0.95 (4)	1.97 (4)	2.897 (4)	165 (3)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

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).

supplementary crystallographic information

Comment

The known anti-tumour activity of L-serine derivatives (Jiao et al., 2009; Yakura et al.,2007) motivates the development of N-acylhydrazone derivatives from L-serine for anti-tumour testing (Pinheiro et al., 2010; de Souza et al., 2010; Pinheiro et al., 2011a; Pinheiro et al., 2011b, de Souza et al., 2011; Howie et al., 2011), and led to the analysis of (I).

The absolute structure of (I) could not be determined experimentally but, the assignment of the S-configuration at the C9 atom is based on a starting reagent, L-serine. The structure of (I), Fig. 1, adopts a curved conformation with both benzene rings lying to the same side of the molecule. The presence of an intramolecular O—H···N hydrogen bond ensures that the hydroxybenzene group is co-planar with the adjacent hydrazine residue with the dihedral angle between the (O2,N1,N2,C7,C8) and (C1–C6) planes being 11.14 (12) °. By contrast, the benzene ring adjacent to the carbamate residue is twisted as seen in the value of the dihedral angle formed between (O4,O5,N3,C11) and (C13–C18) of 50.84 (13) °. The dihedral angle between the two terminal benzene rings is 75.89 (19) °. The molecule is twisted about the chiral centre with the dihedral angle formed between the two amide residues, i.e. N2,C8,O2 and N3,C11,O4, being 80.21 (12) °.

Hydrogen bonds dominate the crystal packing, Table 1. Thus, the secondary hydroxyl group forms a O—H···O hydrogen bond to the hydrazine-carbonyl-O2, and accepts a N—H···.O hydrogen bond from the hydrazine-amine, leading to chains along the c axis. The carbamate-amine forms a N—H···O hydrogen bond to the carbamate-carbonyl-O4, leading to chains along the a axis. The result is the formation of a two-dimensional array in the ac plane, Fig. 2. The layers stack along the b axis, Fig. 3.

Experimental

To a stirred solution of methyl (2S)-2-[(benzyloxycarbonyl)amino]-3-hydroxypropanoate (0.3 g, 1.17 mmol), prepared from (2S)-2-amino-3-hydroxypropanoate hydrochloride and benzyl chloroformate (21 ml, 0.15 mol), in ethanol (10 ml) was added N₂H₄.H₂O (80%, 5.5 mmol). The reaction mixture was stirred for 24 h at room temperature, rotary evaporated and the residue washed with cold ethanol (3 x 10 ml) to give benzyl (1S)-2-hydrazino-1-(hydroxymethyl)-2-oxoethylcarbamate in 78% yield, which was used as such for the next stage. To a stirred solution of (S)-PhCH₂OCONHCH(CH₂OH)CONHNH₂ (1.0 mmol) in ethanol (10 ml) at room temperature was added 2-hydroxybenzaldehyde (1.05 mmol). The reaction mixture was refluxed for 4 h, rotary evaporated and the residue purified by washing with cold ethanol (3 x 10 ml), affording the title compound, M.pt. 433 K, yield 89%. The sample for the structure determination was recrystallized from EtOH to yield colourless laths. ¹H NMR (500 MHz, DMSO-d6) δ (p.p.m.): 11.79 (1H, s, NHN), 11.12 (1H, s, Ph—OH), 8.46 (1H, s, N═ CH, (E)-diastereomer), 7.52 (1H, dd, J = 7.8 and J = 1.5, H6), 7.48 (1H, d, J = 7.8, NHCH), 7.40–7.20 (6H, m, Ph and (H4 or H5)), 6.93–6.84 (2H, m, H3 and (H4 or H5)), 5.05 (3H, m, CH2Ph and OH), 4.13 (1H, m, CH), 3.80–3.60 (2H, m, CH₂OH). ¹³C NMR (125 MHz, DMSO-d6) δ (p.p.m.): 171.6, 157.8, 156.4, 141.2, 137.4, 131.9, 131.6, 129.8, 128.8, 128.3, 128.2, 126.7, 119.9, 119.1, 116.6, 65.9, 61.5, 55.0. IR (cm^-1, KBr): 3312 ν(O—H), 1681 ν(COCH and COO). MS/ESI: [M—H]: 356.3.