Imidazole relative aromaticity

According to the indices, pyrazole is more aromatic than imidazole. The stability of azoles generally increases with an increasing number of aza-groups, though some exceptions are known. The relative aromaticities of triazoles and tetrazole are questionable. 2H-1,2,3-Triazole (/= 88%) which is the more stable in the gas phase reveals more bond levelling than 1//-1,2,3-triazole (1=13%). 

TT-Electron delocalization in isoxazole seems to be more effective than in oxazole however, isothiazole is less aromatic than thiazole thus it is not a general rule that 1,2-diazoles possess higher aromaticity in comparison with 1,3-diazoles. Oxygen-containing heterocycles are always less aromatic than their sulfur and nitrogen counterparts, e.g. thiazole > imidazole > > oxazole. At the same time, the relative aromaticity of S- and N-containing heterocycles can interchange (pyrazole > isothiazole > isoxazole). 

Magnetic criteria have received wide application mainly as a qualitative test for aromaticity and antiaromaticity. The values of the exaltation of diamagnetic susceptibility (in 10-6A cm-3 mol-1), and therefore aromaticity, decrease in the sequence thiazole (17.0) > pyrazole (15.5) > sydnone (14.1). The relative aromaticity of heterocycles with a similar type of heteroatom can be judged from values of the chemical shifts of ring protons. The latter reveals paramagnetic shifts when Tr-electron delocalization is weakened. For example, in the series of isomeric naphthoimidazoles aromaticity decreases in the sequence naphthof 1,2-djimidazole (8 = 7.7-8.7 ppm) > naphtho[2,3- perimidine (8 = 6.1-7.2 ppm). This sequence agrees with other estimates, in particular with energetic criteria. 

The relative aromaticities of isomers of oxygen and sulfur heterocycles can be predicted in a similar way, e.g., thiatriazoles . Of course, the most stable isomer of a pair, as measured by heat of formation, is not necessarily the most aromatic in fact, imidazole (A7/f = 132.9 kj mol ) is thermodynamically more stable than pyrazole (Hf= 179.4 kj mol-1) <1999JPCA9336>. Nevertheless, the empirical rule that 1,2-nitrogen interactions are more favorable for aromaticity than 1,3-nitrogen interactions is a convenient guide to the relative stabilities of closely related azole isomers in the gas phase <2010T2695>. 

The pyrimidine ring system is planar, while the purine system deviates somewhat from planarity in having a slight pucker between its imidazole and pyrimidine portions. Both are relatively insoluble in water, as might be expected from their pronounced aromatic character. 

Two factors are responsible for the high reactivity of the imidazolides as acylating reagents. One is the relative weakness of the amide bond. Because of the aromatic character of imidazole, there is little of the N —> C=0 delocalization that stabilizes normal amides. The reactivity of the imidazolides is also enhanced by protonation of the other imidazole nitrogen, which makes the imidazole ring a better leaving group. 

When formulated into one-component adhesive systems, the product is stable when stored for 6 months to 1 year at room temperature. It will then cure when exposed to 145 to 160°C for about 30 to 60 min. Since the reaction rate is relatively slow at lower temperatures, the addition of 0.2 to 1 percent benzyldimethylamine (BDM A) or other tertiary amine accelerators is common to reduce cure times or cure temperatures. Other common accelerators are imidazoles, substituted urea, and modified aromatic amine. 

Proton loss from cationic species of type (217 Scheme 116) can give rise to relatively stable imines which can be alkylated or acylated with some facility. However, imines are much more common in compounds which are not in tautomeric equilibrium with fully aromatic imidazoles, and among the imidazolidines. 

The tautomerism of these compounds has been discussed in detail in the chapters on structure (Sections 4.01.1.1 and 4.06.5.2), and general reactivities have been considered in Chapter 4.02.3.7 wherein the relative reactivities and interconversions of the hydroxy and carbonyl forms are summarized. Some of the reactions have also been covered in the section dealing with non-aromatic derivatives of imidazoles (Section 4.07.2). Discussion here will be limited to reactions which do not lead to ring fission. 

There has been considerable research into the electrolytic reduction of aromatic carboxylic acids to the corresponding aldehydes. A general procedure has been described in which key elements are the use of the ammonium salt of the acid, careful control of the pH and the presence of an organic phase (benzene) to extract the aldehyde and thus minimize overreduction. The method appears to work best for relatively acidic substrates for example, salicylaldehyde was obtained in 80% yield. Danish workers have shown that, under acidic conditions, controlled electrolytic reductions are possible for certain pyridine-, imidazole- and thiazole-carboxylic acids. In these cases, it is thought that the product aldehydes are protected by geminal diol formation. A chemical method which is closely related to electrolysis is the use of sodium amalgam as reductant. Although not widely used, it was successfully employed in the synthesis of a fluorinated salicylaldehyde. ... 

The catalysis of hydrolysis of carboxylic acid derivatives by weak bases has not been carefully studied until relatively recently. Koshland reported in 1952 the catalysis of acetyl phosphate hydrolysis by pyridine Bafna and Gold (1953) reported the pyridine-catalyzed hydrolysis of acetic anhydride. A short time later the catalysis of aromatic ester hydrolysis by imidazole was demonstrated (Bender and Turnquest, 1957 a, b Bruice and Schmir, 1957). Since that time a large amount of work has been devoted to the understanding of catalyzed ester reactions. Much of the work in this area has been carried out with the purpose of inquiry into the mode of action of hydrolytic enzymes. These enzymes contain on their backbone weak potential catalytic bases or acids, such as imidazole in the form of histidine, carboxylate in the form of aspartate and glutamate, etc. As a result of the enormous effort put into the study of nucleophilic displacements at the carbonyl carbon, a fair understanding of these reactions has resulted. An excellent review is available for work up to 1960 (Bender, 1960). In addition, this subject has been... 

In solution, resonance stabilization (R) is commonly the predominant structural driving force of a reaction. Gas-phase proton-transfer equilibria offer a striking contrast, in which the R effects are frequently found to be secondary to a predominant combination of I and P effects. However, it is recognized that for aromatic compounds, such as, for instance, imidazole, resonance stabilization of the protonated form is the predominant contribution determining the relatively high basicity of imidazole and its congeners in the class of five-membered heteroaromatic compounds. 

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