N-{1-[(3-Bromopropyl)aminocarbonyl]ethyl}-2-(2-nitrobenzenesulfonamido)propionamide

In the title compound, C15H21BrN4O6S, all three NH groups are involved in intermolecular N—H⋯O interactions which, together with two intermolecular C—H⋯O contacts, lead to a continuous antiparallel β-sheet structure. There are no π–π interactions between molecules, and two C—H⋯π interactions primarily govern the linkage between sheets.

In the title compound, C 15 H 21 BrN 4 O 6 S, all three NH groups are involved in intermolecular N-HÁ Á ÁO interactions which, together with two intermolecular C-HÁ Á ÁO contacts, lead to a continuous antiparallel -sheet structure. There are nointeractions between molecules, and two C-HÁ Á Á interactions primarily govern the linkage between sheets.

Comment
The title compound is a precursor for making conformationally restricted dipeptide analogues, which are essential for many molecular recognition events including interactions between antigens and antibodies, peptide hormones and their receptors, and enzymes and their corresponding substrates (Ripka et al., 1993;Belvisi et al., 2000). The dipeptide sequence Ala-Ala has a low frequency of appearance in the conformationally ordered regions of polypeptides (Wilmot & Thornton, 1988;Venkatraman et al., 2001). The sulfonamide group is known to render conformational ordering in peptides and many sulfonamides are crystalline in nature. The title compound was synthesized to investigate the ordering rendered to Ala-Ala dipeptide by the N-nosyl (2-nitro-benzenesulfonylamino) protecting group. In the crystal structure all the three NH groups of the molecule are involved in intermolecular N-H···O interactions.
The two adjacent amide N-H bonds, N 3 -H 3 and N 4 -H 4 , that flank the C-terminal alanine in the title compound are antiperiplanar to each other. The phi, psi angles for the C-terminal alanine are phi = -151.9 (5)°, psi = 130.4 (2)°. These angles and the H3-N3-N4-H4 dihedral angle (166.1 (3)°) are within the limits of those found in b-strand structures (Loughlin et al., 2004). On the other hand, the two adjacent N-H bonds N 2 -H 2 and N 3 -H 3 that flank the N-terminal alanine are slightly distorted away from ideal antiperiplanarity (H2-N2-N3-H3 dihedral angle = 150.2 (5)°). The phi, psi angles for the N-terminal alanine are phi = 95.6 (2)°, psi = 137.8 (7)°. The distortion from the ideal phi value for a beta-strand near N2 is probably due to the fact that N2 is bonded to a sulfonyl group rather than an acyl group.
The strands are arranged in a head-to-tail fashion, with three intermolecular N-H···O interactions and two intermolecular C-H···O interactions (Table 1). These interactions are between adjacent strands and assist in forming a continuous beta-sheet structure. The C1-S1-N2-C7 torsion angle is 62.9 (3)°. This orients the phenyl ring at a dihedral angle of 73.9 (1)° from the mean plane of the rest of the molecule. The crystal structure is stabilized by two C-H···π interactions.
One is intermolecular (C 11 -C g = 3.85 A°, Cg: the centroid of the phenyl ring) and the other is intramolecular (C 11 -C g = 3.92 A°). There are no π-π interactions between the phenyl rings and the interactions between the sheets are solely governed by the C-H···π interactions.

Experimental
To a stirring solution of 2-[2'-(2-nitrosulfonylamido)-propionamido]-propanoic acid (650 mg, 1.88 mmol) in THF (10 ml) at 258 K was added N-methyl morpholene (0.31 ml, 2.82 mmol) followed by ethylchloroformate (0.18 ml,1.93 mmol) under N 2 atmosphere. After two minutes a solution of 3-bromopropan-1-ammonium bromide (536 mg, 2.44 mmol) and N-Methyl morpholene (0.51 ml, 4.7 mmol) in a mixture of DMF/THF (1.5/3 ml) were added to the mixture and stirred for 10 min. The reaction mixture was warmed to room temperature and stirred for further 8 h. THF was removed under reduced pressure and the resulting residue was diluted with EtOAc (10 ml) and washed with saturated aqueous citric acid solution (5 ml), saturated aqueous NaHCO 3 (5 ml) solution and dried (anhydrous Na 2 SO 4 ). The solvent was removed under reduced pressure and the resulting residue was purified by silica gel flash column chromatography (EtOAc/Hexane:1/2) to obtain the title compound sup-2 as a colorless solid 392 mg (0.84 mmol, 45%) (m.p. 404 K). Needle like crystals were obtained for the isolated compound by slow evaporation at room temperature from a solution in 2-propanol (2.1 mM).

Refinement
All the H atoms were positioned geometrically with C-H bond lengths of 0.93 (3)-0.97 (3) Å, and refined using a riding model approximation with U iso (H) = 1.2 U eq (C) or 1.5 U eq (C) for methyl H atoms. Fig. 1. View of the title compound with the atom numbering scheme. Displacement ellipsoids for non-H atoms are drawn at the 50% probability level. H atoms have been omitted for clarity.