Hydrogen Bonds between Acidic Protons from Alkynes (C–H···O) and Amides (N–H···O) and Carbonyl Oxygen Atoms as Acceptor Partners

Crystals of tert-butyl (2S)-2-(prop-2-yn-1-ylcarbamoyl)pyrrolidine-1-carboxylate (Boc-L-Pro-NHCH2CCH) have been obtained. The title compound crystallizes easily as sharp needles in orthorhombic system, space group P 21 21 21 with a = 9.2890(2), b = 9.7292(2), c = 15.7918(4)？？, V = 1427.18(6)？？3, and Z = 4. The main feature of the structure is the orientation of the carbamate and amide. Their dipoles add up and the molecule displays an electric dipole moment of 5.61？D from B3LYP/6-31G(d) calculations. The antiparallel H bonding of amides and the alignment of dipoles induce columnar stacking (the dipole moment along the columnar a axis is 4.46？D for each molecule). The other components across the other axes are, therefore weaker, (3.17？D and 1.23？D along the b and c axes, resp.). The resulting anisotropic columns pack side by side, in an antiparallel fashion mostly by (alkyne) CH···O=C (carbamate) interactions. 1. Introduction The design of organic solid (crystal or supramolecular engineering) is still today challenging and of great importance [1, 2]. Understanding the details of weak intermolecular interactions plays definitely a major role in the rational design of ordered organic crystals. In our lab, we already achieved great molecular macroscopic order with specially designed peptides, macrocycles as precursors to organic nanotubes [3–5] or supramolecular walls [6]. Here, we present the crystal structure of the proline derivative 1 (Figure 1) which alkyne, amide, and carbamate functionalities are all involved in hydrogen bonding. Figure 1: Structure of the proline derivative 1 (Boc-L-ProNHCH 2CCH). 2. Materials and Methods 2.1. Synthesis To Boc-L-proline N-hydroxysuccinimide ester (2.0？g, 6.4？mmol) in CH2Cl2 (40？mL) was added, at 0°C, propargylamine (0.46？g, 8.4？mmol) and K2CO3 (1.43？g, 10.3？mmol). The reaction mixture was allowed to warm up to RT and was stirred for 72？h. Water (30？mL) was added and the organic phase was isolated. The remaining aqueous layer was extracted again with CH2Cl2 ( ？mL). The combined organic layers were filtrated through a cotton plug and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel, eluted with Et2O/Hexane (75？:？25), to yield the title product as a white solid (1.654？g, 78%). (Et2O/Hexane 75？:？25); Tfus (108–111°C); IR (NaCl, ？ cm？1): 3242, 3055, 2982, 2288, 2117, 1688, 1536, 1402, 1324, 1258, 919, 885, and 718. NMR1H (300？MHz, CDCl3, δ ppm): 6.20 (br, 1H), 4.30–3.90 (m, 3H), 3.50–3.30 (m, 2H), 2.40–2.00 (m, 2H), 2.20 (brs, 1H), 2.00–1.80 (m, 2H), and 1.45