guanidines

Guanidines are a class of organic compounds that contain the guanidino functional group, typically represented in the parent compound as HN=C(NH2)2 and in substituted forms as R2N–C(=NH)–NR2. The neutral molecule is planar and participates in extensive resonance among the three nitrogen atoms and the central carbon. In protonated form, the conjugate acid is the guanidinium cation, a highly stabilized resonance-stabilized species.

Guanidines are among the strongest basic compounds known in organic chemistry. They readily accept protons to give guanidinium salts, with a conjugate acid pKa around 13.6 in water for the unsubstituted parent. Substitution on the amino nitrogens modulates basicity and lipophilicity, and many guanidines exist as salts with various acids. In biological systems, the guanidino group is positively charged at physiological pH, enabling interactions with biomolecules and contributing to metal binding and catalysis.

Occurrence and significance: The simplest guanidine is the parent compound itself. The guanidino group is a defining feature of the amino acid arginine, where it exists as a highly basic guanidinium moiety at the side chain. Guanidine motifs appear in numerous natural products and in medicinal chemistry, including drugs and bioactive compounds such as metformin, a biguanide, and other guanidine-containing pharmaceuticals like amiloride.

Synthesis and reactivity: Guanidines are typically prepared by guanidinylation of amines using cyanamides or dicyandiamide derivatives, or via condensation routes from amidines and related reagents. They act as versatile bases, nucleophiles, and guanylating agents in organic synthesis and can serve as ligands in coordination chemistry.