Benzyl N-(1-{N′-[(E)-2-chloro­benzyl­idene]hydrazinecarbon­yl}-2-hy­droxy­eth­yl)carbamate

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

doi:10.1107/S1600536811024895

. 2011 Jun 30;67(Pt 7):o1868–o1869. doi: 10.1107/S1600536811024895

Benzyl N-(1-{N′-[(E)-2-chlorobenzylidene]hydrazinecarbonyl}-2-hydroxyethyl)carbamate

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

PMCID: PMC3151956 PMID: 21837231

Abstract

The molecule of the title compound, C₁₈H₁₈ClN₃O₄, is twisted about the chiral C atom with the dihedral angle between the two amide residues being 87.8 (5)°, but, overall, it can be described as curved, with the benzene rings lying on the same side of the molecule [dihedral angle = 62.8 (4)°]. The conformation about the imine bond [1.294 (7) Å] is E. In the crystal, a two-dimensional array in the ab plane is mediated by O—H⋯O and N—H⋯O hydrogen bonds as well as C—H⋯Cl interactions. The layers stack along the c-axis direction, being connected by C—H⋯.π contacts.

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 ▶); Howie et al. (2011 ▶).

Experimental

Crystal data

C₁₈H₁₈ClN₃O₄
M _r = 375.80
Triclinic,
a = 4.6804 (4) Å
b = 5.6037 (7) Å
c = 16.946 (2) Å
α = 95.669 (6)°
β = 95.886 (7)°
γ = 94.467 (6)°
V = 438.20 (8) Å³
Z = 1
Mo Kα radiation
μ = 0.25 mm⁻¹
T = 120 K
0.12 × 0.03 × 0.02 mm

Data collection

Bruker–Nonius Roper CCD camera on κ-goniostat diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2007 ▶) T _min = 0.682, T _max = 1.000
6351 measured reflections
3438 independent reflections
2520 reflections with I > 2σ(I)
R _int = 0.062

Refinement

R[F ² > 2σ(F ²)] = 0.070
wR(F ²) = 0.196
S = 1.10
3438 reflections
244 parameters
6 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.38 e Å⁻³
Δρ_min = −0.39 e Å⁻³
Absolute structure: Flack (1983 ▶), 1476 Friedel pairs
Flack parameter: 0.15 (12)

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/S1600536811024895/hb5927sup1.cif

e-67-o1868-sup1.cif^{(20.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811024895/hb5927Isup2.hkl

e-67-o1868-Isup2.hkl^{(165.1KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811024895/hb5927Isup3.cml

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

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

Cg1 is the centroid of the C13–C18 benzene ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2o⋯O3ⁱ	0.84 (8)	1.89 (9)	2.728 (7)	171 (9)
N3—H3n⋯O2ⁱⁱ	0.88 (6)	2.20 (6)	3.006 (8)	153 (7)
N2—H2n⋯O1ⁱⁱⁱ	0.88 (3)	1.93 (4)	2.758 (8)	158 (7)
C6—H6⋯Cl^iv	0.95	2.81	3.734 (8)	166
C12—H12b⋯Cg1ⁱⁱⁱ	0.99	2.69	3.474 (8)	137

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

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

Interest in the development of 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; Howie et al., 2011) arises from the known anti-tumour activity of L-serine derivatives (Jiao et al., 2009; Yakura et al., 2007), and motivated the study of the title compound, (I).

Overall, the molecule of (I), Fig. 1, is curved with the benzene rings lying on the same side of the molecule. Nevertheless, the molecule is twisted about the chiral centre with the dihedral angle formed between the two amide residues, i.e. N2,C8,O1 and N3,C11,O3,O4, being 87.8 (5) °. The benzyl group is approximately co-planar with the carboxylate group with the dihedral angle between the carbamate group (N3,C11,O3,O4) and benzene ring (C13–C18) being 9.9 (2) °. By contrast, the benzene ring connected to the hydrazine group is twisted out of the plane through the latter as seen in the value of the C2—C1—C7—N1 torsion angle of 146.7 (5) °. The dihedral angle formed between the terminal benzene rings is 62.8 (4) °. The conformation about the N1═C7 imine bond [1.294 (7) Å] is E.

The crystal packing is dominated by hydrogen bonding interactions, Table 1. The hydroxyl group forms a O—H···O hydrogen bond with the carbamate-carbonyl group, and simultaneously accepts a hydrogen bond from carbamate-amine. The hydrazine-amine forms a N—H···O hydrogen bond with the carbonyl adjacent to the hydrazine group. The result of the hydrogen bonds is the formation of a two-dimensional array in the ab plane, Fig. 2. Additional stabilization to the layer is afforded by C—H···Cl interactions, Table 1. Layers stack along the c direction and are connected via C—H···π interactions, Table 1 and 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-chlorobenzaldehyde (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. 438 K, yield 73%. Yellow needles of (I) for the structure determination were recrystallized from EtOH. ¹H NMR (500 MHz, DMSO-d6) δ (p.p.m.): 11.79 (1H, s, NHN), 8.67 (1H, s, N═CH, (E)-diastereomer), 7.97 (1H, d, J= 6.4, H5), 7.55–7.20 (9H, m, Ph, H2, H3, H4 and NHCH), 5.05 (2H, s, CH₂Ph), 4.94 (1H, m, OH), 4.15 (1H, m, CH), 3.80–3.60 (2H, m, CH₂OH). ¹³C NMR (125 MHz, DMSO-d6) δ (p.p.m.): 172.1, 156.5, 143.5, 137.5, 133.6, 132.0, 131.8, 130.4, 128.8, 128.3, 128.2, 128.1, 127.3, 66.1, 61.9, 57.0. IR (cm^-1, KBr): 3202 ν(O—H), 1682 ν(COCH and COO). MS/ESI: [M—H]: 374.8.