tert-Butyl N-((1S)-2-hy­droxy-1-{N′-[(E)-2-hy­droxy-4-meth­oxy­benzyl­idene]hydrazinecarbon­yl}eth­yl)carbamate

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

doi:10.1107/S1600536811025293

. 2011 Jul 2;67(Pt 8):o1888–o1889. doi: 10.1107/S1600536811025293

tert-Butyl N-((1S)-2-hydroxy-1-{N′-[(E)-2-hydroxy-4-methoxybenzylidene]hydrazinecarbonyl}ethyl)carbamate

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

PMCID: PMC3212283 PMID: 22090940

Abstract

The molecule of the title compound, C₁₆H₂₃N₃O₆, is twisted about the chiral C atom with the dihedral angle formed between the amide residues being 76.9 (3)°. Overall, the molecule is curved with the terminal organic groups lying to the same side. The conformation about the imine bond [1.291 (5) Å] is E and an intramolecular O—H⋯N hydrogen bond generates an S(6) ring. In the crystal, O—H⋯O and N—H⋯O hydrogen bonds involving the hydroxy, amine and carbonyl groups lead to the formation of supramolecular layers, which stack along the c-axis direction.

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 ▶); Tiekink et al. (2011 ▶).

Experimental

Crystal data

C₁₆H₂₃N₃O₆
M _r = 353.37
Triclinic,
a = 5.3101 (14) Å
b = 5.7301 (13) Å
c = 14.651 (4) Å
α = 80.364 (16)°
β = 84.788 (11)°
γ = 74.845 (15)°
V = 423.70 (19) Å³
Z = 1
Mo Kα radiation
μ = 0.11 mm⁻¹
T = 120 K
0.62 × 0.18 × 0.03 mm

Data collection

Bruker–Nonius Roper CCD camera on κ-goniostat diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2007 ▶) T _min = 0.415, T _max = 0.746
7849 measured reflections
1936 independent reflections
1639 reflections with I > 2σ(I)
R _int = 0.092

Refinement

R[F ² > 2σ(F ²)] = 0.062
wR(F ²) = 0.158
S = 1.06
1936 reflections
242 parameters
7 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.32 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/S1600536811025293/hb5936sup1.cif

e-67-o1888-sup1.cif^{(20.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811025293/hb5936Isup2.hkl

e-67-o1888-Isup2.hkl^{(93.3KB, 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	0.84 (5)	1.99 (6)	2.666 (5)	137 (5)
O4—H4o⋯O3ⁱ	0.84 (3)	1.81 (3)	2.607 (5)	157 (6)
N2—H2n⋯O4ⁱⁱ	0.88 (4)	1.92 (3)	2.769 (5)	163 (4)
N3—H3n⋯O5ⁱⁱⁱ	0.88 (4)	2.34 (4)	3.188 (5)	162 (4)

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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 analysis of the title compound, (I), was conducted in the context of developing N-acylhydrazone derivatives from L-serine for use in 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; Tiekink et al., 2011) owing to the known anti-tumour activity of L-serine derivatives (Jiao et al., 2009; Yakura et al., 2007).

The absolute structure of (I) could not be determined experimentally but, the assignment of the S-configuration at the C10 atom is based on a starting reagent, L-serine. The structure of (I), Fig. 1, is isomorphous with the analogue not featuring the hydroxyl group in the ring (Pinheiro et al. 2011b). The molecule adopts a curved conformation with both the benzene ring and tert-butyl group lying to the same side of the molecule. Nevertheless, there is a twist in the molecule, at the chiral centre, as seen in the dihedral angle formed between the two amide residues, i.e. N2,C9,O3 and N3,C12,O5, of 76.9 (3) °. The presence of an intramolecular O—H···N hydrogen bond, Table 1, ensures that the hydroxybenzene group is co-planar with the adjacent hydrazine residue with the dihedral angle between the (O3,N1,N2,C8,C9) and (C1–C6) planes being 9.05 (14) °. The conformation about the N1═C8 imine bond [1.291 (5) Å] is E.

As with related structures in this series, hydrogen bonds dominate the crystal packing, Table 1. 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 b 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 ab plane, Fig. 2. The layers stack along the c axis, Fig. 3.

Experimental

To a stirred solution of (S)-t-BuOCONHCH(CH₂OH)CONHNH₂ (Howie et al., 2011) (1.0 mmol) in ethanol (10 ml) at room temperature was added 2-hydroxy-4-methoxybenzaldehyde (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. 455 K, yield 84%. The sample for the structure determination was recrystallized from EtOH to afford colourless laths of (I).

¹H NMR (500 MHz, DMSO-d6) δ (p.p.m.): 11.60 (1H, s, NHN), 11.46 (1H, s, C1—OH), 8.35 (1H, s, N=CH), 7.39 (1H, d, J = 8.4, H6), 6.84 (1H, d, J = 7.4, NHCH), 6.55–6.40 (2H, m, H3 and H5), 4.98 (1H, m, OH), 4.02 (1H, m, CH), 3.76 (3H, s, CH₃O), 3.70–3.50 (2H, m, CH₂OH), 1.39 (9H, s, (CH₃)₃C). ¹³C NMR(125 MHz, DMSO-d6) δ (p.p.m.): 171.5, 162.5, 158.3, 155.7, 141.8, 128.3, 112.1, 106.9, 101.4, 78.5, 61.6, 56.3, 55.6, 28.6. IR (cm^-1, KBr): 3375 (O—H), 1677 (COCH and COO). MS/ESI: [M—H]: 352.4.