Imidazole chemical properties

Two new sections on the protection for indoles, imidazoles, and pyrroles, and protection for the amide — NH are included. They are separated from the regular amines because their chemical properties are sufficienth different to affect the chemistry of protection and deprotection. The Reactivity Charts in Chapter 8 are identical to those in the first edition. The chart number appears beside the name of each protective group when it is first discussed. 

The chemical structure of histamine has similarities to the structures of other biogenic amines, but important differences also exist. Chemically, histamine is 2-(4-imidazolyl)ethylamine (Fig. 14-1). The ethylamine backbone is a common feature of many of the amine transmitters (e.g. dopamine, norepinephrine and serotonin). However, the imidazole nucleus, absent from other known transmitters, endows histamine with several distinct chemical properties. Among these is prototypic tautomerism, a property that permits it to exist in two different chemical forms (Fig. 14-1). The tautomeric properties of histamine are thought to be critical in the... 

In the same way, the activity of histamine on the Hj receptor is directly correlated with its conformation. That is why the presence of a methyl group in position 4, by modifying the orientation of the imidazole ring relative to the side chain, decreases dramatically the potency of 4-methylhistamine (Table 20.4) on Hj receptor (400-fold less than histamine) whereas its potency on the H2 receptor is almost unchanged. Indeed, a different chemical property is needed at the H2 receptor namely the tautomeric property of the imidazole ring to act as a proton-transfer agent (see Section II.C.). 

Molecules of imidazopyridines 1 and 2 (IP) are built from imidazole and pyridine nuclei that have no common nitrogen atom. This distinguishes imidazopyridines 1 and 2 from imidazo[l,2-a]pyridine 2 and imidazo[l,5-a]pyridine 6. The latter two have little in common with purine in terms of molecular structure and chemical properties (66JOC1295, 67JOC2430). Consequently, imidazopyridines 5 and 6 are not analogues of purine and are not considered here. 

The chemical behaviour of IPs is determined not only by the chemical properties of the imidazole and pyridine rings separately, but also by intramolecular interaction effects (electronic and steric) that arise between the rings in the fused systems. These effects strongly depend both on the electronic condition of the substrate (neutral molecule, cation or anion) and on the geometrical orientation of the rings. IP s behaviour in various reactions will be considered below. We will also examine the behaviour of related heterocycles (for example, pyridine, isoquinoline or triazolo [4,5-c]pyridine, etc.) to illustrate the general or particular character of the IP s properties. 

In this sequence, the pKa of IbP 1 is placed almost exactly between those for purine 3 and benzimidazole 4, and IcP 2 is somewhat closer to purine. These ionization constants give some insight into the influence of the fused rings on the acidity of the imidazole NH. Imidazo[4,5-b]pyridines, and imidazo[4,5-c]-pyridines have more in common with purine in terms of molecular structure and chemical properties than with benzimidazole. 

IC-MS has also been applied for the characterization of ionic liquids (IL) and for the investigation of their long-term stability under process-like conditions. The term ionic liquid commonly refers to a class of molten salts that are by definition liquid below 100 °C. They usually consist of bulky organic cations such as alkylated imidazole, pyrrole, or pyridine derivatives, or quatemized alkyl amines and alkyl phosphines. Common counterions are halides, alkyl sulfates, fluorinated hydrocarbons, carboxylic acids, or amino acids [268]. The physical and chemical properties of ILs are customizable by different cation-anion combinations and by the length of the alkyl chain of the cation. Depending on the... 

ILs have designer properties due to their alterable structures. It was well known that the alkyl chain on an imidazole ring greatly affects the physical and chemical properties of diaUcylimidazolium-based ILs, such as hydrophobicity, viscosities. 

Asher et pointed out that our knowledge of the imidazole ability of n bonding is important for understanding its effect on the physical and chemical properties of hemoproteins. 

---