Nucleophilic substitution imidazoles

Halogen atoms in the 2-position of imidazoles, thiazoles and oxazoles (542) undergo nucleophilic substitution reactions. The conditions required are more vigorous than those used, for example, for a- and y-halogenopyridines, but much less severe than those required for chlorobenzene. Thus in compounds of type (542 X = Cl, Br) the halogen atom can be replaced by the groups NHR, OR, SH and OH (in the last two instances, the products tautomerize see Sections 4.02.3.7 and 4.02.3.8.1). 

Chichibabin reaction, 5, 409-410 UV spectra, 5, 356 Naphthimidazoles, 2-amino-tautomerism, 5, 368 Naphth[2,3-h]imidazoles oxidation, 5, 405 Naphth[l,2-d]imidazolium salts nucleophilic substitution, 5, 412 Naphth[l, 2-h]isoquinolines... 

Imidazole with [Re(CO)3(phen)Cl] or [Re(CO)3(phen)(CF3S03)] in the presence of sulfuric acid gives [Re(CO)3(phen)(im)]2SO (95ICA(240)169). Imidazole with [Mri2(CO) g] gives [Mn2(CO)g(imH)] (84P707). This path involves the nucleophilic substitution of the carbonyl ligand. However, it is complicated by some redox... 

Both electrophilic and nucleophilic reactions can generate halogenopur-ines with differences in regioselectivity dependent on substituents and on the nature of the substrate (anion, neutral molecule, or cation). In the neutral molecule nucleophilic displacements occur in the order 2 > 4 > 6 in the anion the imidazole ring may be sufficiently 7r-excessive for attack to occur at C-2, and the nucleophilic substitution order becomes 4 > 6 > 2. Strong electron donors are usually necessary to promote 2-halogenation by electrophilic halogen sources. 

In Brown s classification a diazonium ion is a reagent of very low reactivity and correspondingly high substrate selectivity and regioselectivity. This follows from the fact that benzenediazonium salts do not normally react with weakly nucleophilic benzene derivatives such as toluene. More reactive heteroaromatic diazonium ions such as substituted imidazole-2-diazonium ions will even react with benzene (see Sec. 12.5). 

Imidazole is a n-electron-excessive heterocycle. Electrophilic substitution normally occurs at C(4) or C(5), whereas nucleophilic substitution takes place at C(2). The order of reactivity for electrophilic substitution for azoles is ... 

The mechanism of hydrolysis of cysteine peptidases, in particular cysteine endopeptidases (EC 3.4.22), shows similarities and differences with that of serine peptidases [2] [3a] [55 - 59]. Cysteine peptidases also form a covalent, ac-ylated intermediate, but here the attacking nucleophile is the SH group of a cysteine residue, or, rather, the deprotonated thiolate group. Like in serine hydrolases, the imidazole ring of a histidine residue activates the nucleophile, but there is a major difference, since here proton abstraction does not appear to be concerted with nucleophilic substitution but with formation of the stable thiolate-imidazolium ion pair. Presumably as a result of this specific activation of the nucleophile, a H-bond acceptor group like Glu or Asp as found in serine hydrolases is seldom present to complete a catalytic triad. For this reason, cysteine endopeptidases are considered to possess a catalytic dyad (i.e., Cys-S plus H-His+). The active site also contains an oxyanion hole where the terminal NH2 group of a glutamine residue plays a major role. 

In many cases the synthesis of NHC complexes starts from iV,A/ -disubstituted azolium salts. Imidazolium salts as precursors for imidazolin-2-ylidenes are generally accessible by two ways complementing each other (i) nucleophilic substitution at the imidazole heterocycle or (ii) a multicomponent reaction building up the heterocycle with the appropriate substituents in a one-pot reaction. 

In general, the 1,3-diazoles do not react by nucleophilic substitution, although imidazole can participate in the Chichibabin reaction with substitution at C-2 the position of substitution is eqmvalent to that noted with pyridine (see Section 11.4.1). Nucleophilic species that are strong bases, like... 

---