Imidazoles 2-methylimidazole

In the case of manganese porphyrin catalyzed epoxidations, the axial ligands have been used alone or together with other additives like carboxylic acids (Banfi and coworkers) and soluble bases (Johnstone and coworkers). For example, Mansny and coworkers showed that in the presence of imidazole, 2-methylimidazole or 4-imidazole chloromanganese(tetra-2,6-dichlorophenylporphyrin) catalyzes the epoxidation of varions aUtenes including 1-alkenes by Under these conditions alkene conversion... 

A study of the kinetics of iodination of 2- and 4-methylimidazoles also demonstrated base-catalyzed iodination, but whereas imidazole and its 2-methyl derivative were subject also to uncatalyzed iodination, 4-methylimidazole was not. Relative rates for base-catalyzed iodination (imidazole 2-methylimidazole 4-methylimidazole) were 1 34 667. For uncatalyzed... 

Vanadium(II) heterocyclic amine complexes of the type [VX2L4] and [VL6]X2 (L = heterocyclic amine, e g. pyrazole, imidazole, 2-methylimidazole, benzimidazole, isoquinoline X = anionic ligand) have been known for some time and more recent examples of such complexes include polypyridyl V complexes of the type [V(terpy)(bipy)L] +. Such complexes are obtained as a result of the disproportionation reaction of [V (terpy)Cl3], which yields [V (terpy)2] + and [V 0] + in CH2CI2 suspensions. ... 

Imidazole, 2-methylimidazole, 2-ethylimidazole, 2-propylimidazole, 2-undecylimidazole, 2-heptadecylimidazole Undecylimidazole... 

Equimolar mixtures of 3,5-dimethylpyrazole with four different NH-imida-zoles have been studied by C and N CP MAS NMR and by DSC. In three cases, the solid mixture behaved as the sum of the individual components [imidazole, 2-methylimidazole and 2,4(5)-dimethylimidazole]. In one case [4,5-dimethylimidazole], the mixture eorresponded to a new species in whieh the dynamic behaviour of 3,5-dimethylpyrazole no longer exists. 

CuO nanoparticles were also found to be effective for the coupling of heterocyclic amines such as imidazole, 2-methylimidazole, and benzimidazole with iodobenzene using 2.5 mol% of catalyst, whereas 1.26 mol% of catalyst was sufficient for pyrrole and indole (Fig. 2). 

Fig. 2 Coupled products of heterocyclic amines (left to right) pyrrole, indole, imidazole, 2-methylimidazole, and benzimidazole with iodobenzene catalyzed by CuO nanoparticles...

Methylimidazole (51) with chloroform in the vapor phase gave, among other products, 2-chloro-3-methylpyrazine (52) (550°C, flow system 17%) n other such reactions with imidazole, methylimidazoles, and methylimidazo-... 

Gas-phase pK values for azoles are unavailable except for imidazole and 1-methyl-imidazole. Imidazole is ca. 75kJmor more basic than ammonia, i.e. approximately the same as pyridine 1-methylimidazole is about 29kJmor more basic than imidazole (82PC40200). 

Annular tautomerism of azoles and benzazoles [the nonaromatic tautomers of imidazole 17, 2H and 4(5)H have been calculated at the MP2/6-31G level to be about 15 kcal mol less stable than the IH tautomer (95JOC2865)]. We present here the case of 4(5)-substituted imidazoles, different from the histamine, histidine, and derivatives already discussed. By analogy with these histamines, 4-methylimidazole 17a is often named distal [N(t)H] and 5-methylimidazole 17b, proximal [N(7t)H] (Scheme 9). 

By far the most common starting material is l-methylimidazole. This is readily available at a reasonable cost, and provides access to the majority of cations likely to be of interest to most researchers. There is only a limited range of other N-substituted imidazoles commercially available, however, and many are relatively expensive. The synthesis of l-alkylimidazoles may be achieved without great difficulty, though, as indicated in Scheme 2.1-2. 

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. 

When the aromatic group of the sulfoxide is replaced by a heteroaromatic group (e.g., N-methylimidazole), the internal coordination between Li—N to form a five-membered metallocycle apparently predominates over Li—O coordination to form a four-membered metallocycle . Reaction of imidazole (S)-sulfoxide 16 with benzaldehyde produces aldol 17 as the major product in which the a-H and the sulfoxide lone pair are syn (equation 14) imidazole (R)-sulfoxide 18 reacts similarly (equation 15). The stereochemical outcome of these reactions is rationalized in terms of a-lithiosulfoxides in which the reactive diastereomer (i.e., 20 and 21) is that having one diastereotopic face of the five-membered Li—N metallocycle carrying both H and sulfoxide lone pair. 

The amino acid 58 was used in the solid-phase synthesis of sequence-specific DNA binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids <96JACS6141> and it was also reported that the imidazole-acridine conjugate 59 could effectively catalyze the cleavage of t-RNA <96TL4417>. 

THF, tetrahydrofuran DMF, dimethylformamide DMSO, dimethyl sulfoxide DPSO, diphenyl sulfoxide en, ethylenediamine py, pyridine pic, picoline lut, lutidine nic, nicotinamide IMD, imidazole MelMD, N-methylimidazole 1-Cl-nap, 1-chloronaph-thyl acac, acetylacetonyl anion, CH3COCHCOCH3 C4H9O3, acetoacetic ester anion, CH3COCHCOOC2HS C4H,oN2, piperazine C7HSN2, benzimidazole. 

Klejdus, B. et al.. Solid-phase extraction of 4(5)-methylimidazole (4-MeI) and 2-acetyl-4(5)-(l,2,3,4-tetrahydroxybutyl)-imidazole (THI) from foods and beverages with subsequent liquid chromatographic-electrospray mass spectrometric quantification, J. Sep. ScL, 29, 378, 2006. 

The l-acyl-3-methylimidazole-2-thiones are easily obtained either from bis-l-methyl-2-imidazole disulfide, a carboxylic acid, and triphenylphosphine, or from 2-mercapto-l-methylimidazole and a carboxylic acid chloride in the presence of triethylamine.[32 ... 

For this reason the regioselective methylation of various 4-substituted 1-acetyl-imidazoles was studied.1[2] While reaction with l-acetyl-4-phenylimidazole furnished the isomers l-methyl-5-phenylimidazole and l-methyl-4-phenylimidazole in a ratio of 93 7, reaction with l-acetyl-4-methylimidazole produced an isomer ratio of 86 14. 

Upon recrystallization, [Ni(tpzlmtacn)]2+ affords [Ni(L)(MeCN)]2+ (L = l,4-bis(pyrazol-l-ylmethyl)-l,4,7-triazacyclononane) via a N-dealkylation reaction and loss of a pendent arm.1420 More rational routes to Ni complexes of tacn ligands with only one or two pendent arms have been developed.1431,1432 In [Ni(L)(X) ]x (e.g., L= l-(3-aminopropyl)-l,4,7-triazacyclononane (n = 2) or l-(l-methylimidazol-2-ylmethyl)-l,4,7-triazacyclononane (n = 2) or l,4-bis(l-methyl-imidazol-2-ylmethyl)-l,4,7-triazacyclononane (n = 1), the coordination sphere is completed by additional ligands that bind either terminal (X = C1 , H20) or bridge two metal ions (X = N3 , OH, oxalate). The Ni11 complex of l,4-bis(2-pyridylmethyl)-l,4,7-triazacyclononane has been shown to be extremely inert to ligand dissociation in aqueous solution.1433 In (562), the tacn ligand provides a single bidentate arm.1434... 

The zinc bis(tetraseleno) anion, [Zn(Se4)2]2-, has been crystallized with a number of cations, synthesized by a variety of methods, and its reactivity studied.581-584 The compound (hexaseleno) (tetraseleno)zinc (64) was synthesized from zinc acetate in the presence of lithium polyselenide and structurally characterized, demonstrating seven-membered and flve-membered ZnSen rings.585 Mixed donor neutral monomers have also been formed with imidazole A-donor ligands, ZnSe4 (A-methylimidazole)2.553... 

Equations (12.36) and (12.40) are the basis of the LRA method for calculating pi a shifts [59]. Indeed, to obtain the pKa shift due to the protein environment, we perform the same calculation for the protein and for a small molecule in solution, analogous to the side chain of interest. For a histidine side chain, for example, one would choose imidazole or methylimidazole in solution as a model compound. The pKa shift due to the protein environment will then have the form ... 

A rather complex microwave-assisted ring-opening of chiral difluorinated epoxy-cyclooctenones has been studied by Percy and coworkers (Scheme 6.131) [265]. The epoxide resisted conventional hydrolysis, but reacted smoothly in basic aqueous media (ammonia or N-methylimidazole) under microwave irradiation at 100 °C for 10 min to afford unique hemiacetals and hemiaminals in good yields. Other nitrogen nucleophiles, such as sodium azide or imidazole, failed to trigger the reaction. The reaction with sodium hydroxide led to much poorer conversion of the starting material. 

By the same procedure, crystalline picrates of 5-amino- 1-cyclohexyl-2-methylimidazole (112 R = Me) (45%) [71JCS(C)1501] and 5-amino-l-(2-pyridyl) imidazole (96 R1 = pyrid-2-yl, R2 = H) (20%) [80JCS(P1)2316] were obtained from the sodium salts of the corresponding acids. 

Biosynthesis is performed in one step by the enzyme L-histidine decarboxylase (HDC, E.C. 4.1.1.22). Histamine metabolism occurs mainly by two pathways. Oxidation is carried out by diamine oxidase (DAO, E.C. 1.4.3.6), leading to imidazole acetic acid (IAA), whereas methyla-tion is effected by histamine N-methyltransferase (HMT, E.C. 2.1.1.8), producing fe/e-methylhistamine (t-MH). IAA can exist as a riboside or ribotide conjugate. t-MH is further metabolized by monoamine oxidase (MAO)-B, producing fe/e-methylimidazole acetic acid (t-MIAA). Note that histamine is a substrate for DAO but not for MAO. Aldehyde intermediates, formed by the oxidation of both histamine and t-MH, are thought to be quickly oxidized to acids under normal circumstances. In the vertebrate CNS, histamine is almost exclusively methylated... 

The synthesis of methylimidazole-thiophene compounds was reported by Santos et al. [46] and has been included for completeness, although no biological activity has been reported for these heterocycles. The formation of these imidizole-thiophenes (24a-d), occurs via the condensation of 2-formylthiophene (25) with benzil derivatives (26a-d) in the presence of ammonium acetate to yield the imidazole-thiophene compounds (27a-d). These compounds can then be N-methylated by treatment with iodomethane in... 

Steric factors play an important role in reactions of bromomethylaqua-cobaloxime with substituted imidazoles - 1-methylimidazole reacts at approximately the same rate as imidazole itself, but the presence of an alkyl substituent in the 2-position of the incoming imidazole reduces the rate dramatically (72). 

Treating imidazole with iodine in an NaOH solution afforded the complete ring iodination product, 2,4,5-triiodoimidazole. 4-Iodoimidazole was then produced in 75% yield upon selective reductive deiodination, [5]. The same procedure converted 2-methylimidazole and 1-methylimidazole to 4(5)-iodo-2-methylimidazole [6] and 4(5)-bromo-l-methylimidazole [7], respectively. 

Nonetheless, to make imidazole-containing molecules, haloimidazoles may serve as electrophilic coupling partners for the Suzuki reaction. As described in section 9.1, regioselective bromination at the C(4) position could be achieved for a 1,5-dialkylimidazole using NBS in CH3CN. The Suzuki coupling of l-benzyl-4-bromo-5-methylimidazole with phenylboronic acid assembled the unsymmetrical heterobiaryl in 93% yield, whereas the corresponding Stille reaction with phenyltrimethyltin proceeded in only moderate yield (51%) [8]. 

Generally, the intermolecular Heck reaction between 2-iodo-, 4-iodo- and 5-iodo-l-methylimidazoles and olefins suffers from low yields (< 25%). Therefore, these transformations are of limited synthetic utility [29]. In one case, variable yields for adduct 62 (15-58%) were observed for the Heck reaction of 5-bromo-l-methyl-2-phenylthio-lf/-imidazole (61) and a large excess of methyl acrylate [42]. 

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