Imidazoles alkyl

Imidazole, 4-acetyl-5-methyl-2-phenyl-synthesis, 5, 475 Imidazole, 1-acyl-reactions, 5, 452 rearrangement, 5, 379 Imidazole, 2-acyl-synthesis, 5, 392, 402, 408 Imidazole, 4-acyl-synthesis, 5, 468 Imidazole, C-acyl-UV spectra, 5, 356 Imidazole, N-acyl-hydrolysis rate constant, 5, 350 reactions, 5, 451-453 synthesis, 5, 54, 390-393 Imidazole, alkenyl-oxidation, 5, 437 polymerization, 5, 437 Imidazole, 1-alkoxycarbonyl-decarboxylation, 5, 453 Imidazole, 2-alkoxy-l-methyl-reactions, 5, 102 thermal rearrangement, 5, 443 Imidazole, 4-alkoxymethyl-synthesis, 5, 480 Imidazole, alkyl-oxidation, 5, 430 synthesis, 5, 484 UV spectra, 5, 355 Imidazole, 1-alkyl-alkylation, 5, 73 bromination, 5, 398, 399 HNMR, 5, 353 synthesis, 5, 383 thermal rearrangement, 5, 363 Imidazole, 2-alkyl-reactions, 5, 88 synthesis, 5, 469... 

Imidazole, 4-alkyl-synthesis, 5, 482 Imidazole, 5-alkyl-synthesis, 5, 481 Imidazole, N-alkyl-metallation, 5, 415-416 reactions, 5, 449-450 synthesis, 5, 387 Imidazole, 1 -alkyl-5-amino-synthesis, 5, 462... 

Cobalt, Co " (cf ) 4, tetrahedral 5 -Thiolate, thioether, N-imidazole Alkyl group transfer, oxidases... 

Imidazole alkylations can be carried out under a variety of reaction conditions. For conventional iV-alkylations which are unlikely to be complicated in terms of regiochemistry, it is preferable to alkylate the imidazole anion (an Se2cB process). Such reactions are faster, higher yielding and less prone to azole salt formation than those in neutral conditions. The anion is generated best by the use of sodium in ethanol or liquid ammonia, with sodium or potassium hydroxide or carbonate, or by use of sodium hydride in dry DMF [3]. Addition of the alkylating agent to the deprotonated substrate completes the reaction. 

By analogy to imidazoles, alkylation by haloalkanes of benzimidazoles on the N-atom occurs in neutral and in basic media. 1-Alkylbenzimidazoles are obtained from benzimidazole, sodium hydroxide and bromoalkanes. Benzimidazoles unsubstituted in the 1-position undergo the Mannich reaction ... 

Classic A/-heterocychc ligands, eg, bipyridyl (bipy), terpyridyl, imidazole, pyrazine, phenanthroline, piperazine (including alkyl- and aryl-substituted derivatives), and polypyrazol-l-yl-borates (bis, tris, and tetra), have all been found to coordinate Th(IV) chlorides, perchlorates, and nitrates. The tripodal hydrotris(pyrazolyl)borates, HBPz, have been used to stabilize organometaHic complexes (31). Bis-porphyrin Th(IV) "sandwich" complexes have been... 

Data taken from <71pmhi3i297), which contains references to the original literature. Simple alkyl- and aryl-imidazoles. iV-Unsubstituted compounds are IV-acylated prior to injection. 

Pyrazoles and imidazoles carrying a substituent on nitrogen, as well as oxazoles, thiazoles, etc., are converted by alkyl halides into quaternary salts. This is Illustrated by the preparation of thiamine (89) from components (87) and (88). 

Pyrazoles and imidazoles with free NH groups are readily alkylated, e.g. by Mel or Me2S04. A useful procedure is to use the alkyl salt of the azole in liquid ammonia (80AHC(27)241). However, alkylation can also occur under neutral conditions, particularly with imidazoles. 

Since /V-acylation is a reversible process, it has allowed the regiospecific alkylation of, for example, imidazoles to give the sterically less favored derivative. This principle is illustrated in Scheme 7 (80AHC(27)24l). 

Under alkaline conditions, alkyl nitrites nitrosate imidazoles which possess a free NH group in the 4-position (70AHC(12)103). Nitrosation of 3,5-dimethylpyrazole gives the 4-diazonium salt by further reaction of the nitroso compound with more NO". 5-Pyrazolinones are often nitrosated readily at the 4-position. 3-Alkyl-5-acetamidoisothiazoles undergo 4-nitrosation. 

Alkyl radicals produced by oxidative decarboxylation of carboxylic acids are nucleophilic and attack protonated azoles at the most electron-deficient sites. Thus imidazole and 1-alkylimidazoles are alkylated exclusively at the 2-position (80AHC(27)241). Similarly, thiazoles are attacked in acidic media by methyl and propyl radicals to give 2-substituted derivatives in moderate yields, with smaller amounts of 5-substitution. These reactions have been reviewed (74AHC(i6)123) the mechanism involves an intermediate cr-complex. 

In addition to the reactions described in the preceding section, alkyl groups in the 2-positions of imidazole, oxazole and thiazole rings show reactions which result from the easy loss of a proton from the carbon atom of the alkyl group which is adjacent to the ring (see Section 4.02.3.1.2). 

Amidines and related systems such as guanidines react with a-halogenoketones to form imidazoles. a-Hydroxyketones also take part in this reaction to form imidazoles, and a variety of substituents can be introduced into the imidazole nucleus by these procedures. Reaction of the a-halogenoketone (73) with an alkyl- or aryl-substituted carboxamidine (76) readily gave the imidazole (77) (01CB637, 48JCS1960). Variation of the reaction components that successfully take part in this reaction process is described in Chapter 4.08. 

Sulfur may also be alkylated under appropriate conditions. On formation, the N-/3-chloroethylthiazolidine-2-thione (307) underwent spontaneous ring closure to the tetrahy-drothiazolo[2,3-6]thiazolylium chloride (308) (71CHE1534) and a similar reaction occurred in the imidazole series. 

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