Synthon preference in O-protonated amide crystals - dominance of short strong hydrogen bonds

Although the amide functional group is weakly ionizable, there have been serendipitous discoveries of amide salts. To facilitate their systematic design, we sought to identify the preference of 12 possible synthons in oxygen protonated amide structures. An analysis of a total of 81 protonated amide crystal structures retrieved from the Cambridge Structural Database and 12 new protonated amide structures prepared by us, revealed that similar to 86% of these structures involving charge assisted short strong hydrogen bonds, including similar to 54% of the hydrogen bridged dimers formed between protonated and neutral amide. The probability of forming hydrogen bridged dimers increases in the order of primary amide < secondary amide < tertiary amide. The two previously missing synthons, R-2(2)(8) and R-2(1)(6), in primary amides are realized for the first time in this work. However, the two predicted ring (R) hydrogen bonding synthons, R-2(2)(8) and R-2(1)(6), for cis secondary amides remain to be discovered.