amidine

Amidine refers to compounds with the functional group C(=NH)NR2, where R and R' are hydrogen or organic groups. The simplest members are primary amidines (R-C(=NH)NH2); secondary and tertiary amidines have one or two substituents on the imine nitrogen. In neutral form amidines are typically planar and exhibit resonance between C=N and C–N bonds; upon protonation they form amidinium cations, accounting for their high basicity.

Amidines are among the more basic nitrogen-containing functionalities. The conjugate acids often have pKa values around 10–12, making neutral amidines strongly basic and often protonated under physiological conditions. They are good hydrogen-bond donors and acceptors and can act as ligands in coordination chemistry. In medicinal chemistry, amidine motifs appear in protease inhibitors and other pharmacophores; benzamidine is a widely used simple model compound.

Synthesis and preparation: Amidines are typically prepared by amidination of carbonyl- or nitrile-derived precursors, using reagents such as ammonia, primary amines, cyanamides, carbodiimides, or imidoyl chlorides. These routes provide broad access to aryl- and alkyl-substituted amidines for use in synthesis, catalysis, and pharmaceutical research.

Related groups and occurrences: The amidine motif is related to the guanidine group; guanidines are fully substituted amidines. The arginine amino acid contains a guanidinium moiety. Amidines are mainly synthetic building blocks, though they also appear in natural products and as functional groups in various bioactive compounds.