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

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

doi:10.1107/S1600536811024263

. 2011 Jun 25;67(Pt 7):o1805–o1806. doi: 10.1107/S1600536811024263

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

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

PMCID: PMC3151906 PMID: 21837178

Abstract

The molecule of the title compound, C₁₆H₂₃N₃O₅, is twisted about the chiral C atom, the dihedral angle formed between the amide residues being 79.6 (3)°. The conformation about the imine bond [1.278 (5) Å] is E. In the crystal, O—H⋯O and N—H⋯O hydrogen bonding between the hydroxy, amine and carbonyl groups leads 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 ▶, 2011 ▶); de Souza et al. (2010 ▶); Howie et al. (2011 ▶).

Experimental

Crystal data

C₁₆H₂₃N₃O₅
M _r = 337.38
Triclinic,
a = 5.3323 (4) Å
b = 5.7200 (4) Å
c = 14.3319 (10) Å
α = 79.919 (4)°
β = 83.686 (4)°
γ = 76.505 (4)°
V = 417.41 (5) Å³
Z = 1
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 120 K
0.16 × 0.07 × 0.04 mm

Data collection

Bruker–Nonius Roper CCD camera on κ-goniostat diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2007 ▶) T _min = 0.887, T _max = 1.000
7495 measured reflections
1900 independent reflections
1661 reflections with I > 2σ(I)
R _int = 0.046

Refinement

R[F ² > 2σ(F ²)] = 0.051
wR(F ²) = 0.113
S = 1.09
1900 reflections
230 parameters
6 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.25 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/S1600536811024263/hb5921sup1.cif

e-67-o1805-sup1.cif^{(20.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811024263/hb5921Isup2.hkl

e-67-o1805-Isup2.hkl^{(91.6KB, 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
O3—H3o⋯O2ⁱ	0.84 (3)	1.87 (3)	2.651 (4)	153 (4)
N2—H2n⋯O3ⁱⁱ	0.88 (3)	1.93 (3)	2.803 (4)	169 (3)
N3—H3n⋯O5ⁱⁱⁱ	0.88 (3)	2.34 (3)	3.188 (4)	164 (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 anti-tumour activity of L-serine derivatives (Jiao et al., 2009; Yakura et al.,2007) and 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., 2011: Howie et al.,2011) is well documented.

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. The synthetic protocols led to the formation of both the E and Z isomers (see Experimental). Recrystallization provided one isomer only, with the conformation about the N1═C8 imine bond [1.278 (5) Å] being E. The molecule is twisted about the chiral centre as seen in the value of the N2—C9—C10—N3 torsion angle of 77.5 (4) °; the dihedral angle formed between the two amide residues, i.e. N2,C9,O2 and N3,C12,O5, is 79.6 (3) °. This arrangement precludes the formation of intramolecular hydrogen bonds. The methoxy residue is co-planar with the benzene ring to which it is attached as seen in the C7—O1—C4—C3 torsion angle of -0.5 (5) °.

The crystal packing is dominated by hydrogen bonding interactions whereby each of the acidic hydrogen atoms forms a hydrogen bond. Thus, the hydroxy-OH forms a hydrogen bond with the hydrazine-carbonyl, and at the same time accepts a hydrogen bond from the hydrazine-amine. The carbamate-amine forms a hydrogen bond with the carbamate-carbonyl; details are given in Table 1. The hydrogen bonding leads to layers in the ab plane, Fig. 2, which stack along the c axis, Fig. 3.

Experimental

A reaction mixture of (S)-t-BuOCONHCH(CH₂OH)CONHNH₂ (1.0 mmol), prepared from L-serine (Howie et al., 2011), and 4-methoxybenzaldehyde (1.05 mmol) in EtOH (10 ml) was refluxed for 4 h. The reaction mixture was rotary evaporated, and the residue was purified by washing with cold ethanol (3 x 10 ml): M.pt. 409 K, yield 80%. The solution NMR spectra in DMSO-d6 solution indicated the presence of both E and Z isomers. On recrystallization from EtOH for the structure determination, only the E isomer was obtained. ¹H NMR (400 MHz, DMSO-d6): δ (p.p.m.): 11.28 and 11.21 (1H, s, NHN, E & Z isomers), 8.17 and 7.92 (1H, s, N=CH, E & Z isomers), 7.63 (1H, s, H1 or H5), 7.61 (1H, s, H1 or H5), 7.00 (2H, m, H2 and H4), 6.73 (d, J= 7.4) and 6.58 (d, J= 8.6), (1H, NHCH, E & Z isomers)), 4.91 (m) and 4.76 (t, J= 6.6), (1H, OH, E & Z isomers)), 4.91 and 4.02 (1H, m, CH, E & Z isomers)), 3.80 (3H, s, CH₃O), 3.70–3.50 (2H, m, CH₂OH), 1.39 (9H, s, (CH₃)₃C–). ¹³C NMR (100 MHz, DMSO-d6) δ (p.p.m.): 171.3 and 166.9 (COCH, E & Z isomers), 160.7 and 160.6 (C3, E & Z isomers), 155.2 (COO), 146.6 and 143.0 (N=CH, E & Z isomers), 128.5 and 128.3 (C1 and C5), 126.8 (C6), 114.3 (C2 and C4), 78.2 and 78.0 ((CH₃)₃C–, E & Z isomers)), 61.6 and 61.2 (CH₂OH, E & Z isomers), 56.0 and 54.0 (CH, E & Z isomers), 55.3 (CH₃O), 28.1 ((CH₃)₃C). IR (cm^-1, KBr): 3306 (O—H), 1697 (COCH), 1678 (COO). EM/ESI: [M—H]: 336.1.