Imidazoles, 4-diazo

H-Imidazol 4-Diazo-5-ethoxycar-bonyl- E14b, 1312 (NH2 - N2) 9H-Purin... 

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... 

Imidazole, 4-methyl-annular tautomerism, 5, 363 association, 5, 362 boiling point, 5, 362 bromination, 5, 398 deuteration, 5, 417 diazo coupling, 5, 403 hydrogen bonding, S, 350 hydroxymethylation, 5, 404 iodination, 5, 400 kinetics, 5, 401 mass spectra, 5, 358 melting point, 5, 362 methylation, 5, 364 sulfonation, 5, 397 synthesis, 5, 479-480, 482, 484, 489 Imidazole, 5-methyl-annular tautomerism, 5, 363 Imidazole, l-methyl-4-chloro-ethylation, 5, 386 Imidazole, l-methyl-5-chloro-ethylation, 5, 386 nitration, 5, 395... 

The tetracyano derivative of 2.49, 5-diazo-l,2,3,4-tetracyanocyclopentadiene (2.52), and its heterocyclic analogue, 2-diazo-4,5-dicyano-imidazole (2.53) can be obtained by diazotization of the corresponding amines, namely the (anionic) 1-amino-... 

Aromatic diazonium salts react easily in neutral aqueous solution with thiols such as N-acetylcysteine, forming compounds of the type Ar — N2 —S —CH2CH(NHAc) COOH. Nifontov et al. (1990) suggested that such compounds, e.g., that of 5-diazo-imidazole-4-carboxylate, function as a form of transport depot for cytotoxic diazo-carboxylate in the human body. 

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)). 

The only problem for the matrix-isolation of 21 consisted in the non-availability of a reasonable diazo precursor molecule suited for this technique. But since we already had experience with the preparation of 2,3-dihydrothiazol-2-ylidene46 (see below) by photofragmentation of thiazole-2-carboxylic acid we tried the same method with imidazole-2-carboxylic acid (20). Indeed, irradiation of 20 with a wavelength of 254 nm leads to decarboxylation and the formation of a complex between carbene 21 and CO2. This is shown by the observation that the experimental IR spectrum fits only with the calculated spectrum of complex 21-CC>2 (calculated stabilization energy relative to its fragments 4.3 kcal mol-1). The type of fixation of CO2 to 21 is indicated in the formula S-21 C02. 

Four 4-diazo-1,2,3-triazole derivatives, though stable in dichloromethane solution, exploded violently when heated as solids [1], Several diazo-triazoles, -pyrazoles and -imidazoles were found to be explosively unstable in varying degrees [2],... 

Diazo-4,5-dicyanoimidazole in acetic acid decomposed to the corresponding imidazole, but in hot water or aqueous acetic acid it gave quantitative evolution of nitrogen and intractable tars (79JOC1717). 4-Diazoi-midazole-5-carboxamide treated with 30% sulfuric acid at 95°C in the presence of copper bronze did not give the hydroxy compound, but cy-clized to 2-azahypoxanthine, the same compound obtained by thermolysis and photolysis in acid [81JCS(P1)1433]. 

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 2-diazo-4-R-imidazoles (R = H, CH2COOH) showed sufficient stability in neutral medium to be tested in binding experiments for the rat brain y-aminobutyric acid (GABA) receptor (87JMC2222). They had an ICso of 5.10" M and 7.10 M, respectively, and they recognized the GABA receptor. Therefore they can be used as potential irreversible probes for this receptor. 

Auch bei der Umsetzung von 4-Methyl-benzolsulfonsaure-imidazolid und Kalium-imidazolid mit Diphenyl-methanol wird C-Alkylierung beobachtet. Hier entsteht ein Gemisch aus 1-(22%), 2- (12%) und 4(5)-Diphenylmethyl-imidazol (24%)845. Beim Belichten von Imidazol und Diazo-diphenyl-methan in Tetrahydrofuran entsteht das gleiche Produktgemisch845. 

Mit N(a)-tert.-Butyloxycarbonyl-2-diazo-L-histidin-methylester gelingt auch die Isolierung der 2-Diazo-Verbindung eines Histidin-Derivates1069. 5-Aminocarbonyl-4-diazo-imidazol reagiert mit Hydrazin zu 5(4)-Aminocarbonyl-4(5)-azido-imidazoli06 1069. 

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