Synthesis of imidazolines from nitrile and from ester precursors.
A variety of routes exist for the synthesis of imidazolines,[1][2] with the most common methods involving the condensation of 1,2-diamines (e.g. ethylenediamine) with nitriles or esters. The nitrile based route is essentially a cyclic Pinner reaction; it requires high temperatures and acid catalysis and is effective for both alkyl and aryl nitriles.
As natural products
Imidazoline has been found in various natural products. Natural molecules topsentin D and spongotine B were discovered in several marine sponges. These metabolites have received considerable attention because of their potent properties such as antitumor, antiviral, and anti-inflammatory activities.[3]
2-imidazolines have been investigated as antihyperglycemic, anti-inflammatory, antihypertensive, antihypercholesterolemic, and antidepressant reagents.[1][5] The imidazoline-containing drug clonidine is used alone or in combination with other medications to treat high blood pressure. It is also used in the treatment of dysmenorrhea, hypertensive crisis, Tourette's syndrome and attention deficit hyperactivity disorder (ADHD).[6]
Cis-imidazolines act as small-molecule antagonists of MDM2. These compounds bind MDM2/X in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice. The most active compounds are nutlin-3a[7] and rg-7112,[8] but some other analogs also activate p53.[9][10][11]
Surfactants
Surfactants based around 2-imidazoline, such as sodium lauroamphoacetate, are used in personal care products where mildness and non-irritancy are particularly important (e.g. baby products, "no more tears" shampoos etc.).[12]
As precursors of imidazoles
Imidazoles can be prepared from dehydrogenation of imidazolines.[13]
^ abcdLiu H, Du DM (March 2009). "Recent Advances in the Synthesis of 2-Imidazolines and Their Applications in Homogeneous Catalysis". Advanced Synthesis & Catalysis. 351 (4): 489–519. doi:10.1002/adsc.200800797.
^Guinchard X, Vallée Y, Denis JN (May 2007). "Total synthesis of marine sponge bis(indole) alkaloids of the topsentin class". The Journal of Organic Chemistry. 72 (10): 3972–3975. doi:10.1021/jo070286r. PMID17444688.
^Dardonville C, Rozas I (September 2004). "Imidazoline binding sites and their ligands: an overview of the different chemical structures". Medicinal Research Reviews. 24 (5): 639–661. doi:10.1002/med.20007. PMID15224384. S2CID31258438.
^Ishihara M, Togo H (2006). "An Efficient Preparation of 2-Imidazolines and Imidazoles from Aldehydes with Molecular Iodine and (Diacetoxyiodo)benzene". Synlett (2): 227–230. doi:10.1055/s-2005-923604.
