tert-Butyl N-{(1S)-1-[(2,4-dihydroxybenzylidene)hydrazinecarbonyl]-2-hydroxyethyl}carbamate ethanol monosolvate

The molecule of the title ethanol solvate, C15H21N3O6·C2H6O, adopts a curved shape; the conformation about the imine bond [N=N = 1.287 (3) Å] is E. The amide residues occupy positions almost orthogonal to each other [dihedral angle = 85.7 (2)°]. In the crystal, a network of O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds leads to the formation of supramolecular arrays in the ab plane with the ethanol molecules lying to the periphery on either side. Disorder in the solvent ethanol molecule was evident with two positions being resolved for the C atoms [site occupancy of the major component = 0.612 (10)].

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). Comment 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 antibiotic 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 Nacylhydrazones 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-tumoural activities (Rollas et al., 2007;Terzioğlu et al., 2003). In continuation of on-going structural studies of these compounds , we now report the structure of the ethanol solvate of tert-butyl

tert-Butyl N-{(1S)-1-[(2,4-dihydroxybenzylidene)hydrazinecarbonyl]-2-hydroxyethyl}carbamate
Although the absolute structure of (I), Fig. 1, could not be determined experimentally, the assignment of the S-configuration at the C9 atom is based on a starting reagent. The overall conformation of the molecule is curved with the major kink occurring at the C9 atom. The dihydroxybenzene ring is slightly twisted out of the plane of the hydrazine residue with the C2-C1-C7-N1 torsion angle being -8.2 (3) °. The conformation about the N1-C7 imine bond [1.287 (3) Å] is E.
Each of the carbonyl groups is diagonally opposite the amine group and the dihedral angle formed between the two amide residues is 85.7 (2) °.
As expected with four hydroxyl and two amine donors, there is significant hydrogen bonding operating in the crystal structure, Table 1. While the O1-hydroxy group forms an intramolecular O-H···N hydrogen bond with the hydrazine-N1 atom, the remaining interactions are intermolecular in nature. The O2-hydroxy group forms an O-H···O hydrogen bond with the O5-carbonyl, and the O3-hydroxyl group linked to the chiral centre is connected to the ethanol molecule which in turn forms a hydrogen bond to the O2-hydroxyl group. The N2-amine is connected to the O3-carbonyl and the N3-amine forms a hydrogen bond with the O4-hydroxyl. The result of the hydrogen bonding is the formation of layers of molecules in the ab plane sandwiched by ethanol molecules. The layers stack along the c axis, Fig. 2.
The O-and N-bound H atoms were located from a difference map and refined with the distance restraints O-H = 0.84 ± 0.01 and N-H = 0.86±0.01 Å, and with U iso (H) = zU eq (carrier atom); z = 1.5 for O and z = 1.2 for N. Disorder was resolved in the solvent ethanol molecule in that two distinct positions were discerned for the C atoms. From fractional anisotropic refinement, the major component had a site occupancy factor = 0.612 (10). In the absence of significant anomalous scattering effects, 2067 Friedel pairs were averaged in the final refinement. However, the absolute configuration was assigned on the basis of the chirality of the L-serine starting material. The maximum and minimum residual electron density peaks of 0.61 and 0.33 e Å -3 , respectively, were located 0.42 Å and 0.37 Å from the H6 and H16a atoms, respectively. Fig. 1. The molecular structure of (I) showing displacement ellipsoids at the 50% probability level. The ethanol molecule of solvation has been omitted.  Atomic displacement parameters (Å 2 )