Imidazole 5-alkyl-4-aryl

A number of microwave-assisted multicomponent methods for the synthesis of imidazoles have been reported [68-71 ]. The irradiation of a 1,2-diketone and aldehyde with ammonium acetate in acetic acid for 5 min at 180 °C in a single-mode reactor provides alkyl-, aryl-, and heteroaryl-substituted imidazoles 39 in excellent yield (Scheme 14) and this method has been used for the rapid and efficient preparation of two biologically active imidazoles, lepidiline B and trifenagrel [68]. 

The reaction of 1-amino-1-deoxyketoses, and their N-alkyl and N-aryl derivatives, with alkyl or aryl isothiocyanates (Huber et al, 1960) was studied in more detail, and new 4-(alditol-l-yl)-l-alkyl(aryl)-3-alkyl(aryl)-l,3-dihydro-2H-imidazole-2-thiones were obtained. These compounds were used as starting materials for the synthesis of OL-histidines, DL-histidine-2-thiol, and other imidazole derivatives of biological interest. 

Direct coupling of imidazole with aryl iodides in the presence of copper(I) triflate results in 1-aryl-imidazoles, which can be alkylated in a second step [Eq. (5)]. This route represents a variation of the Gridnev method. ... 

Aryl-imidazole konnen direkt aus Alkyl-aryl-ketonen in einer Eintopfreaktion durch Bromierung in Formamid und anschlieBende Cyclisierung unter Durchleiten von Ammoniak hergestellt werden48. 

For nonsymmetrical bicyclic imidazoles, direct TV-alkylation (arylation or acylation) is problematic since site-selectivity is influenced by many subtle electronic effects. Thus, Curtius rearrangement-based syntheses have been used widely for the synthesis of differentiated TV-substituted thienoimidazoles (104), (106) from (acylamido)thiophene carbonyl azides (103), (105) (Equations (30) and (31)) <79JCR(S)96>. These intermediates are useful for the synthesis of angiotensin II antagonists (Equation (32)) <91EUP483683,92EUP520423>. 

It appears that mass spectrometry is of considerable value in structure determination although, at present, it is not possible to differentiate between 2- and 4-substituted isomers. The technique has been used to establish the structure of 4-(imidazol-4-yl)butane-1,2,3-triol55 which, unlike most carbohydrate derivatives, shows a molecular ion. The mass spectra of 2-alkylbenzimidazoles246 and mercaptoimidazoles124 have been examined, while use has been made of mass spectrometry in the identification of some alkyl, aryl, and acyl imidazoles.138... 

In an endeavor to study the transmission of substituent effects in imidazoles Noyce (73JOC3762) examined the solvolysis rates of a series of l-(l-methylimidazolyl)ethyl p-nitrobenzoates (75-77 OPNB = p-nitrobenzoate). The relative rates (75 76 77 = 1 13 15) parallel the relative electron densities in 1-methylimidazole as deduced from chemical shift data. By comparison with other heteroarylethyl p-nitrobenzoates the effective replacement constants, crXr, were determined as a-2-im = —0.82, o-J-im = —1.01 and <7-5.1 = —1.02. The effects on the 2-substituted compound of alkyl, aryl and halogen substituents at the 4- and 5-positions were examined, but though the rates for the 5-substituents could be represented satisfactorily by cTp, substituted compounds. It is not surprising that the distorting effects of annular heteroatoms make it difficult to superimpose the substitution behavior of benzenoid compounds into this series. 

Both imidazole-2- and -4-carbaldehydes resist the Cannizzaro, Perkin and benzoin reactions, but the 1-substituted compounds react normally. 1-Substituted 5-nitroimidazole-2-aldehydes condense readily with alkyl aryl ketones. Examples of successful condensations... 

By careful control of metallating agent, blocking groups and reaction conditions, it is possible to make 2-alkyl(aryl)thio- and 4(5)-alkyl(aryl)thioimidazoles in high yields, e.g. l-trityl-2-phenylthio- [3], 4(5)-methylthio- [4] and l-benzyl-2,4,5-tris(methylthio)-imidazole [5]. 

The effects on the 2-substituted compound of alkyl, aryl, and halogen substituents in the imidazole ring have also been examined, and although the rates for the 5-substituents were represented satisfactorily by quantum-mechanical calculations of 7c-electron densities for the imidazole neutral molecule predict the order of substitution as 5 > 4 > 2, but the tautomeric equivalence of the 4- and 5-positions is not taken into account. In addition, there are probably few occasions on which electrophilic substitution takes place with the neutral molecule the conjugate acid or conjugate base may be the reactive species. 

In Table A.l the chemical environment of each bond is normally defined by a linear formulation of the substructure. The target bond is set in bold type, e.g. Cgr-C N (aryl cyanides) C-CH2-0-Cgr (primary alkyl aryl ethers) (C-0)2-P( = 0)2 (phosphate diesters). Occasionally the chemical numbering of a functional group or ring system is used to define bond environment, e.g. in naphthalene, C(2)-C(3) in imidazole N1-C2. To avoid any possible ambiguity in these cases, we include numbered chemical diagrams in Figure A.4. A combination of chemical name and linear formulation is often employed to increase the precision of the definition, e.g. NH2-C=0 in acyclic amides C = C-C( = 0)-C(=0) in benzoquinones. Finally, for very simple ions the accepted conventional representation is deemed to be sufficient, e.g. in N03, S04, etc. 

Methyl-l-organo-4,5-dihydro-imidazoliuin-jodide allgemeine Vorschrift 0,1 mol l-Alkyl(Aryl)-4,5-dihydfo-imidazol wird mit 142 g (1 mol) Methyljodid in 150 ml Dichlormethan versetzt und 1 -2 Stdn. zum Sieden erhitzt. Losungsmittel und Methyljodid werden abdestilliert, der Riickstand mit Ether verriihrt und abgesaugt Ausbeuten 80-95%. 

The use of a,P-unsaturated 2-acylimidazoles [151] as the dienophile increased the practicality of the approach, since the imidazole group can be removed readily from the product. The substrate scope is quite broad substituents at the alkene moiety (e.g., alkyl, aryl and 2-furanyl) were very well tolerated, hi all cases good to excellent enantioselectivies and diastereoselectivities were obtained, i.e., 80-98% ee for the endo isomer and endo. exo > 94 6, in the case of the 4,4 -dimethyl-2,2 -bipyridine ligand [152]. Moreover, the D-A reaction was successfully performed on a preparative scale (1 mmol), making it attractive from a synthetic point of view. 

In an analogous approach, the effect of imidazole was also observed by Inoue et al. [114]. When alkyl aryl sulfides were oxidized with a novel iron porphyrin catalyst (52) (0.2 mol% equiv), the reaction proceeded enantioselectively under appropriate conditions. Iodosobenzene was used as oxidant in dichloromethane at -43°C. The turnover number increases to 142, and an ee of 73% was obtained in the presence of a 100 to 600 molar ratio of imidazole to catalyst for the synthesis of (5)-methoxymethyl phenyl sulfoxide. In the absence of imidazole, the enantioselectivity disappeared, giving the racemic sulfoxide. 

The (SIPr)Pd(cinnamyl)Cl (SlPr= l,3-bis(2,6-diisopropyl phenyl)-4,5-dihydro imidazol-2-ylidene) catalysed anaerobic oxidation of aryl/alkyl, aryl/aryl, and alkyl/ alkyl secondary alcohols to the corresponding ketones in high yields has been achieved using aryl chlorides in toluene with f-BuONa. Domino Pd-catalysed synthesis of a-arylated ketones from secondary aryl alcohols in very good yields was also reported. " ... 

N-Substitut0d PBI The NH groups in the imidazole rings are chemically reactive. For some applications, the chemical reactivity can be reduced by, for example, replacement of the hydrogen of the imidazole ring with less reactive substituents such as hydroxyethyl [179], sulfoalkyl [180,181], cyanoethyl [182], and phenyl [183], as well as alkyl, alkenyl, or aryl [184] groups. The methods developed by Sansone et al. [180-184] use a PBI solution in DMAc or 7V-methyl-pyrrilidone. The unsubstituted PBI is first reacted with an alkah hydride to produce a polybenzimidazole polyanion, which is then reacted with a substituted or unsubstituted alkyl, aryl, or alkenyl methyl halide to produce an iV-substituted PBI, as shown in Fig. 4.13. 

Cellulose is a natural biopolymer, which is biodegradable, environmentally safe, widely abundant, inexpensive, and easy to handle [57]. Cellulose and its derivatives are widely used in chemical and bio-chemical applications and also as supports for the synthesis of organic molecules [58]. Interestingly, the cellulose fibers also act as a nanoreactor for the stabilization of metal nanoparticles [59]. However, its use as a support for catalytic applications is not well explored. Recently, Choplin and coworkers reported cellulose as the support for water soluble Pd(OAc>2/5 TPPTS system in the Trost-Tsuji allylic alkylation reaction [60]. To corroborate the above concept in the cross coupling of aryl halides and boronic acids, we reported A-arylation of imidazoles with aryl halides using a cellulose-supported Cu(0) catalyst (CELL-Cu(O) [61]. The prepared catalyst was well characterized using various instrumental techniques. For example, the X-ray diffraction pattern of CELL-Cu(O) catalyst clearly indicates the presence of Cu (111) and Cu (200) phases which are attributed to Cu(0) [46]. Further, the high resolution XPS narrow scan spectrum of the fresh CELL-Cu(O) catalyst shows a Cu 2p3/2 peak at 932.72 ev, which is attributed to Cu (0) [22]. 

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. 

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. 

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