Aromaticity of imidazoles

Fig. 5 Isomerization stabilization energy, an isodesmic reaction applied to evaluate the aromaticity of imidazole-ylidenes...

Imidazole and its derivatives form an interesting and important class of hetero cyclic aromatic amines Imidazole is approximately 100 times more basic than pyndme... 

The systems discussed here are aromatic systems which undergo a variety of isomerizations on irradiation. Irradiation of imidazoles led to a scrambling of substituents, whereas such scrambling has not been observed in the pyrazoles which undergo photoisomerization to imidazoles. 

When the aromatic group of the sulfoxide is replaced by a heteroaromatic group (e.g., N-methylimidazole), the internal coordination between Li—N to form a five-membered metallocycle apparently predominates over Li—O coordination to form a four-membered metallocycle . Reaction of imidazole (S)-sulfoxide 16 with benzaldehyde produces aldol 17 as the major product in which the a-H and the sulfoxide lone pair are syn (equation 14) imidazole (R)-sulfoxide 18 reacts similarly (equation 15). The stereochemical outcome of these reactions is rationalized in terms of a-lithiosulfoxides in which the reactive diastereomer (i.e., 20 and 21) is that having one diastereotopic face of the five-membered Li—N metallocycle carrying both H and sulfoxide lone pair. 

R = Aromatic R = H, aliphatic, yields 85-90% Scheme 13 Synthesis of imidazoles on alumina... 

Analogous to the synthesis of isocyanates, isothiocyanates are obtained in good yield by reacting AyV -thiocarbonyldiimidazole (ImCSIm) with primary aliphatic or aromatic amines in equimolar amount. In chloroform at room temperature the dissociation equilibrium of imidazole-A-thiocarboxamides is shifted completely to isocyanates. 

The most common methods suitable for the synthesis of different azolium compounds will be discussed here. Two routes are particularly useful for the preparation of the imidazolium salts (1) substitution reactions at the nitrogen atoms of imidazole [25] and (2) multicomponent reactions for the generation of an Af,Af -substituted heterocycle which are particularly useful for the synthesis of imidazolium salts bearing aromatic, very bulky, or particularly reactive N,N -sub-stituents (Fig. 3a,b) [26]. Both methods offer the opportunity to produce unsym-metrically substituted imidazolium salts of type 1 either by stepwise alkylation of imidazole or by the synthesis of an W-arylated imidazole derivative followed by 77 -alkylation [27]. Nevertheless, the method of choice for the preparation of the imidazolium salts 1 is the 77,77 -substitution of imidazole. Several other methods for the preparation of imidazolium salts with previously unattainable substitution patterns have also been described [28, 29]. 

From the reaction of imidazole 161 and aromatic acid halides (Scheme 63), imidoyl chlorides 162 are obtained, which eliminate methyl chloride to form imidazo[2,l-6]l,3,4]thiadiazoles 163 upon extended heating (88H1935). 

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. 

Is the stability of 8Ad due to unfavorable kinetics, i.e., the bulky adamantyl groups blocking reaction, or to unfavorable thermochemistry, i.e., loss of aromaticity of the imidazole ring as a result of reaction, or both The distinction is potentially important as understanding could assist in designing stable carbenes. To decide, compare the kinetics and thermodynamics of the insertion of 8Ad into the central CH bond in propane with reactions of 8Me, which should also be aromatic but lacks shielding groups , and 9, which is neither aromatic nor crowded. 

The inverse electron demand Diels-Alder [4- -2]-cycloaddition of imidazoles to electron-poor dienes to yield imidazo[4,5-i pyridazines, reported in CHEC-II(1996), has been further developed. It was reported that the reaction of267 with tetrazines 268 was fruitless. However, 267 reacted with excess of 268 to yield aromatic 271 along with 1,4-dihydrotetrazine 270. Most likely, 271 arose from dehydrogenation of first-formed 269 by an extra equivalent of 268 <2001T5497> (Scheme 18). 

Heinemann, C., Mueller, T., Apeloig, Y. et al.. On the question of stability, conjugation, and aromaticity in imidazol-2-ylidenes and their silicon analogs, /. Am. Chem. Soc., 118, 2023,1996. 

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