Imidazole halides

In contrast to the scarcity of precedents in the imidazolylboronic acids, abundant reports exist on imidazolylstannanes. In the Stille reaction, the imidazole nucleus may serve as either the nucleophile as an imidazole halide or the electrophile as an imidazolylstannane. One advantage of the Stille reaction is that it often tolerates delicate functionalities in both partners. 

Transition metal catalyzed coupling reactions 4.02.5.5.4(i) Palladium mediated coupling of N-protected imidazole halides 4.02.5.5.4(i)(a) Heck coupling... 

Diarylimidazoles were prepared by Suzuki cross-coupling reactions of imidazole halides with arylboronic acids <05H(65)1975>. Suzuki cross-coupling reactions of 6-bromoimidazo[l,2-a]pyridines have been developed <05H(65)2979>. Cul-catalyzed iV-arylation of imidazoles and benzimidazoles with aryl bromides was achieved in a near-homogeneous system that utilized tetraethylammonium carbonate as base, 8-hydroxyquinoline as ligand and water as cosolvent <05JOC10135>. 

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). 

Azoles containing a free NH group react comparatively readily with acyl halides. N-Acyl-pyrazoles, -imidazoles, etc. can be prepared by reaction sequences of either type (66) -> (67) or type (70)->(71) or (72). Such reactions have been carried out with benzoyl halides, sulfonyl halides, isocyanates, isothiocyanates and chloroformates. Reactions occur under Schotten-Baumann conditions or in inert solvents. When two isomeric products could result, only the thermodynamically stable one is usually obtained because the acylation reactions are reversible and the products interconvert readily. Thus benzotriazole forms 1-acyl derivatives (99) which preserve the Kekule resonance of the benzene ring and are therefore more stable than the isomeric 2-acyl derivatives. Acylation of pyrazoles also usually gives the more stable isomer as the sole product (66AHCi6)347). The imidazole-catalyzed hydrolysis of esters can be classified as an electrophilic attack on the multiply bonded imidazole nitrogen. 

Displacement of bromine on phenacyl halide with imidazole gives Reduction with sodium borohydride followed by displacement with 2,6-dichloro-benzyl alcohol in HMPA then produces antifungal orconazole (37). ... 

Insertion of a triazole ring in place of an imidazole ring is consistent in some cases with retention of antifungal activity. The synthesis of one such agent, azoconazole (64), proceeds simply by displacement of halide with 1,2,4-triazole. The route to terconazole (65) is rather like that to ketoconazole (34). ... 

Hardacre et al. have developed a procedure for the synthesis of deuterated imidazoles and imidazolium salts [65]. The procedure involves the platinum- or palladium-catalyzed deuterium exchange of 1-methyl-d -imidazole with D2O to give 1-methylimidazole-d , followed by treatment with a deuterated alkyl halide. 

Poly (ethylene oxide) macromonomers72 761 are made in a similar way, as the alkoxide end group is reactive enough towards benzylic halides. With methacryloyl chloride, side reactions are involved. It is better to first protonate the PEO, and then to have it react with methacryloyl chloride in the presence of some triethyl amine. One can also react co-hydroxy polyethylene oxide) with methacryloyl imidazole, or with methacrylic acid in the presence of dicyclohexyl carbodiimide (DCCf)77). 

In vanadium-dependent haloperoxidases, the metal center is coordinated to the imidazole system of a histidine residue, which is similarly responsible for creating hypochlorite or hypobromite as electrophilic halogenating species [274]. Remarkably, a representative of this enzyme class is capable of performing stereoselective incorporation of halides, as has been reported for the conversion of nerolidol to various snyderols. The overall reaction commences through a bromonium intermediate, which cyclizes in an intramolecular process the resulting carbocation can ultimately be trapped upon elimination to three snyderols (Scheme 9.37) [275]. 

Other examples of nucleophilic attack on the oxirane ring include the formation of (3-halohydrins with silica-gel supported lithium halides <96TL1845>, the addition of amines catalyzed by lithium triflate, an ersatz for lithium perchlorate <96TL7715>, and the addition of pyrroles, indoles and imidazoles under high pressure i.e., 91 —> 93) <96JOC984>. 

In addition to acyl halides and acid anhydrides, there are a number of milder and more selective acylating agents that can be readily prepared from carboxylic acids. Imidazolides, the (V-acyl derivatives of imidazole, are examples.115 Imidazolides are isolable substances and can be prepared directly from the carboxylic acid by reaction with carbonyldiimidazole. 

Allylation of acyloyl-imidazoles and pyrazoles61 with allyl halide mediated by indium in aqueous media provides a facile regioselective synthesis of P, y-unsaturated ketones (Scheme 11.1), which has been applied to the synthesis of the monoterpene artemesia ketone. The same product can be obtained by indium-mediated allylation of acyl cyanide (Eq. 11.35).62 Samarium, gallium, and bismuth can be used as a mediator for the allylation of nitrones and hydrazones to give homoallylic hydroxylamine and hydrazides in aqueous media in the presence of Bu4NBr (Scheme 11.2).63 The reaction with gallium and bismuth can be increased dramatically under microwave activation. 

A modification of this method, related to the Beckmann rearrangement, entails treatment of a ketoxime with one equivalent of CDI, then four to five equivalents of a reactive halide such as allyl bromide or methyl iodide (R3X) under reflux in acetonitrile for 0.5-1.5 h. Quatemization of the imidazole ring effectively promotes the reaction by increasing the electron-withdrawing effect. The target amides then are obtained by hydrolysis. High yields, neutral conditions, and a very simple procedure make this modification of the synthesis of amides by azolides a very useful alternative. 1243... 

By reaction of the appropriate aromatic sulfomc acid halide or anhydride with imidazole[1] Toluenesulfonic lmidazolide was obtained from toluenesulfomc anhydride in very good yield... 

Imidazole- and Triazole-Transfer Reactions to Tertiary Alcohols, Halides, and Acetates... 

Table 21-1. Halides prepared from alcohols via imidazole-V-carboxylates, -sulfonates and -sulfinates.

Carbene complexes have also been prepared by transmetallation reactions. Lithiated azoles react with gold chloride compounds and after protonation or alkylation the corresponding dihydro-azol-ylidene compounds, e.g., (381) or (382), are obtained.22 9-2264 Silver salts of benz-imidazol have also been used to obtain carbene derivatives.2265 Mononuclear gold(I) carbene complexes also form when trimeric gold(I) imidazolyl reacts with ethyl chlorocarbonate or ethyl idodate.2266,2267 The treatment of gold halide complexes with 2-lithiated pyridine followed by protonation or alkylation also yields carbene complexes such as (383).2268 Some of these carbene complexes show luminescent properties.2269-2271... 

As a further approach for novel electrolytes appropriate for selective cation transport, we have prepared poly(organoboron halide)-imidazole complexes.35 Even though boron-amine complexes are widely known materials reported by the early works of H. C. Brown et al.,52-54 they had not been investigated as solvents or electrolytes to the best of our knowledge. 

It is known that organoboron halide-imidazole complexes dissociate diming equilibrium 56 however, charges disappear upon dissociation. In such a matrix, mobile ions should not originate from the matrix. Therefore, the polymer electrolytes composed of boron halide-imidazole complexes were considered to be appropriate for selective ion transport. 

Figure 5 Temperature dependence of ionic conductivity for poly(organoboron halide)-imidazole complexes in the presence of various lithium salts.

Figure 6 VFT plots for poly(organoboron halide)-imidazole complexes. 

Table 2 VFT Parameters for Poly(organoboron halide)-imidazole Complexes...

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