Amidines

Amidines

Amidines are a class of compounds in organic chemistry characterized by the functional group consisting of a carbon atom connected to a nitrogen atom (C=N) which is in turn bonded to two other nitrogen atoms. They are considered the nitrogen analogs of carboxylic acids and amides, where the oxygen atom in these compounds is replaced by a nitrogen atom. Amidines are represented by the general formula R-C(=NR')NR2, where R, R', and R can be hydrogen atoms, alkyl, or aryl groups.

Structure and Bonding

The central carbon-nitrogen double bond (C=N) in amidines is shorter and stronger than the carbon-nitrogen single bond found in amides due to the presence of resonance structures that delocalize the lone pair of electrons on the nitrogen across the C=N bond. This delocalization contributes to the stability of amidines and affects their chemical properties. The nitrogen atoms in amidines are sp² hybridized, leading to a trigonal planar geometry around the carbon-nitrogen double bond.

Synthesis

Amidines can be synthesized through several methods. One common approach is the reaction of nitriles with amines in the presence of a strong base. This method typically involves the deprotonation of the amine to form an imine, which then reacts with the nitrile to form the amidine. Another method involves the reaction of an amide with a more reactive amine, a process known as amidation.

Reactivity and Applications

Amidines are basic compounds due to the electron-donating effect of the nitrogen atoms, making them more nucleophilic than amides. They can act as ligands in coordination chemistry, forming complexes with metals. Amidines are also used as catalysts in a variety of organic reactions, including the synthesis of other nitrogen-containing compounds.

In the pharmaceutical industry, amidines have found applications as active pharmaceutical ingredients. Some amidines are used as antifungal agents, while others have been investigated for their antiviral and antibacterial properties.

Examples

• DBU (1,8-Diazabicyclo[5.4.0]undec-7-ene) and DBN (1,5-Diazabicyclo[4.3.0]non-5-ene) are amidines that serve as strong, non-nucleophilic bases in organic synthesis.
• Pentamidine is an example of a diamidine that is used as an antifungal and antiprotozoal medication.
• Benzamidine is a simple amidine that acts as a reversible inhibitor of serine proteases, such as trypsin and thrombin.

Environmental and Safety Considerations

The synthesis and use of amidines must be conducted with consideration for environmental and safety impacts. Some amidines may be toxic or hazardous, requiring appropriate handling, storage, and disposal practices to minimize risks to human health and the environment.