Boc-AzAla-Ala-OMe

The title compound (systematic name: tert-butyl 3-{[1-(methoxycarbonyl)ethyl]aminocarbonyl}-3-methylcarbazate), C11H21N3O5, is a precursor for the study of a new class of foldamer based on aza/α-dipeptide oligomerization [Abbas et al. (2009 ▶). Tetrahedron Lett. 50, 4158–4160]. The asymmetric unit consists of one molecule in an extended conformation which is stabilized by intermolecular N—H⋯O and C—H⋯O hydrogen bonding.


Comment
As part of our continuing studies on the synthesis and structure of hydrazino-and N-amino-peptides, we recently described the original and efficient synthesis of aza/α-dipeptides via Mitsunobu and trans-protections protocols starting from N-tertbutyloxycarbonylaminophtalimide (Abbas et al., 2009;Majer & Randad 1994;Brosse et al. 2001;Bouillon et al. 2004).
Aza-peptides are pseudopeptides, in which nitrogen has been substituted for at least one of the CH α groups. Here we report the crystal structure of the pseudodipeptide Boc-AzAla-Ala-OMe (Fig. 1).
In the present study, the geometry of the aza-residue is similar to those observed for known azapeptides structures. In most of the cases, the α-nitrogen adopts a non-planar planar structure (André et al., 1996;Benatalah et al. 1991). In the title compound, the deviation of the α-nitrogen out of the plane, defined by the three atoms bonded to it, is 0.268 (2) Å. The greatest difference from standard peptide group concern the bond lengths and bond angles around the α-nitrogen: (i) the N-N α (N1-N2) and N α -C β (N2-C6) bonds are shorter by about 0.06Å than their homologous bonds in peptides; (ii) the N α -C' ((N2-C7) bond of 1.392 (3)Å is shorter than the homologous C α -C' bond and exceeds the dimension of the amide bond; (iii) the bond angles around the α-nitrogen are larger by 5-6° than the bond angles around the α-carbon.
In the solid state, Boc-AzAla-Pro-NHiPr (André et al., 1997) and the title compound Boc-AzAla-Ala-OMe adopt two distinct conformations with the N α atoms having opposite configurations. In the former, the AzAla residue assumes the R chirality and the pseudodipeptide is folded by an intramolecular hydrogen bond between the (iPr)NH and the Boc(CO) groups. In the crystal of the title compound, the pseudodipeptides adopt an extended conformation which form infinite chains along the four fold axis. The N-H goups of AzaAla and Ala residues are engaged in intermolecular hydrogen bonds with the carbonyl groups of the N-terminal protecting group and the aza-residue, respectively, forming two C(4) chain motifs (Fig. 2, Etter 1990). Combination of these two motifs generates a new R 2 2 (12) pattern, shown in the Fig. 2. Finally, the third carbonyl group, C10=O4, is involved in weak CH···O hydrogen bonds forming a threedimensional network structure.

Experimental
The title compound was prepared from N-tert-butyloxycarbonylaminophtalimide (Abbas et al., 2009), and was crystallized by slow evaporation of a diethyl ether solution.

Refinement
Because of the lack of any significant anomalous dispersion effects, the absolute configurations of the title compound could not be determined from the diffraction experiments but was known from the method of synthesis. The origin was fixed by floating-origin restraints (Flack & Schwarzenbach, 1988). All H atoms were located in difference Fourier maps. The C/N-bonded H atoms were placed at calculated positions and refined using a riding model, with C-H distances of 0.96-0.98 supplementary materials sup-2 Å and with N-H distance of 0.86 Å. The H-atom U iso parameters were fixed at 1.2Ueq(C) for methine C-H, at 1.2Ueq (N) for the N-H group and at 1.5Ueq(C) for methyl C-H. Fig. 1. The molecular structure of the title compound showing the atom-numbering scheme. All non-H atoms are represented by 25% probability displacement ellipsoids.