Imidazoles, diazo-, reactions

The electrophilic carbene, 4H-imidazolylidene (63), has been prepared by photodecomposition of 4-diazo-4H-imidazole (64). Reaction with cyclohexane affords the C-H insertion product, 4(5)-cyclohexylimidazole (65), whereas reaction with benzene yields 4(5)-phenylimidazole (66). Analogous addition of 4H-imidazolylid-ene to derivatives of benzene is influenced by the presence and nature of the substituents. 

Pyrazoles and imidazoles exist partly as anions (e.g. 108 and 109) in neutral and basic solution. Under these conditions they react with electrophilic reagents almost as readily as phenol, undergoing diazo coupling, nitrosation and Mannich reactions (note the increased reactivity of pyrrole anions over the neutral pyrrole species). 

Diazo coupling is expected to occur only with highly reactive systems, and experiment bears this out. Diazonium ions couple with the anions of N-unsubstituted imidazoles at the 2-position (e.g. 125 yields 126) and with indazoles (127) in the 3-position. In general, other azoles react only when they contain an amino, hydroxyl, or potential hydroxyl group, e.g. the 4-hydroxypyrazole (128), the triazolinone (129) and the thiazolidinedione (130) (all these reactions occur on the corresponding anions). 

Benzenediazonium fluoroborate, 2-carboxy-xanthone synthesis from, 3, 838 Benzenediazonium ions phenyl azide formation from, 5, 839 Benzenediazonium salts, o-(imidazol-l-yl)-intramolecular diazo coupling, 5, 404 Benzene-1,2-disulfonimides N-substituted reactions, 6, 930 Benzene episulfide formation, 7, 577 Benzeneimine... 

Since the regioselectivity of mercuration reactions is often hard to control, recent efforts have focused on the use of Lewis-basic substituents whose role is to direct the approach of the mercuric ion to a specific position. Reaction of the diazo derivative 74 with Hg(OAc)2 leads to mercuration of the naphthalene moiety in the 8-position rather than mercuration of the electron-rich imidazole carbon atoms. 4 Presumably, the diazo-imidazole bidentate moiety coordinates to the mercuric cation, thereby directing substitution at the naphthalene 8-position (Equation (27)). 

Both 3-diazO 1,2,4-triazoles and 4-diazo-l,2,3-triazoles easily give cycloaddition reactions with ynamine leading to 4-aminotriazolo-triazine 284 and the yields are generally higher than in the pyrazole and imidazole series (77S556) (Scheme 85). 

The above considerations do not necessarily apply to reactions of electrophilic reagents with pyrazole and imidazole anions (134, 135). The imidazole anion is sometimes (diazo coupling, halogenation, deuterium exchange) substituted in the 2-position (139) and the indazole anion in the 3-position (cf. Section 3.4.1.4.5). 

As in the reaction of imidazole, no major isotope effect has been observed 3-deuterioindole reacts at about the same rate as indole. The diazo coupling of five-membered heteroaromatic substrates therefore appears similar to that of homocyclic compounds where, in the absence of steric hindrance, slow attack of the diazonium ion is followed by a fast proton loss.165... 

These orientations of substitution are observed when either the neutral or the protonated molecules are the reacting species. On the other hand, different orientations can be observed in those reactions of imidazole (and perhaps pyrazole) which involve the dissociated anions C3H3N2-. For example, diazo coupling96 and deuterium exchange203 of imidazole in alkaline media give rise to 2-substitution. 

This report covers two topics (1) The generation of 2-thioxo-2,4-dihydro-3fT-imidazol-l-ium-l-imides as intermediates in the course of [3+2] cycloaddition reactions of azoalkenes and thiocyanic acid resulting in the formation of l-aminoimidazole-2-thione derivatives some further reactions of these heterocycles are presented as well. (2) The rhodium-catalyzed intramolecular interaction of co-diazenyl a -diazo ketones giving rise to the formation of mostly two cyclic azomethine imine isomers with an exocyclic terminal nitrogen atom and with all three... 

Semi-empirical LCAO calculations for all azoles, introducing cr-electrons, indicate that charges are weak except those on NH nitrogen atoms, and that the cr-dipolar moments are close to those of lone pairs. It is therefore inappropriate to take cr-polarity into account in the approximations used in 7r-calculations for these heterocycles. A number of other quantum mechanical calculations have been applied to reactions of imidazoles (80AHC 27)241), while the nucleophilic substitution reactions at C-2 of benzimidazoles, and diazo coupling at C-2 of uncondensed imidazoles have been discussed from theoretical points of view. 

In contrast to the neutral molecule of imidazole, the conjugate base is highly susceptible to electrophilic attack, particularly on one or other of the annular nitrogen atoms. Thus, alkylation occurs very rapidly in basic medium. There are also some electrophilic substitution reactions at ring carbon atoms which involve the heterocyclic anion, e.g. diazo coupling and iodination. 

Unsubstituted imidazole reacts with most electrophiles preferentially at C-4(5), but in neutral or basic media it is often difficult to prevent multiple substitution, e.g. halogenation. Deuterium exchange is unusual in that 2-exchange is more facile than 4- or 5-exchange, and diazo coupling occurs with about equal facility in both 2- and 4-positions. Acidic reagents almost always involve the protonated imidazole (imidazolium) as the reactive species. In this form the reactivity is greatly decreased, and 4(5)-substitution is observed, e.g. nitration and sulfonation. Friedel-Crafts reactions will not occur at all. Under severe conditions, disubstitution may be possible. 

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