Imidazoles methylation

Needle like nanoparticles of Mg-Al mixed spinel catalysts synthesized under hydrothermal conditions were used for the synthesis of 1-methylimidazole by the gas phase imidazole methylation with methanol performed at atmospheric pressure [113]. High yield and selectivity to desired product were obtained at a temperature range between 320 and 350°C. It was proposed that one of the nitrogen atoms participates in the bonding of the imidazole with the basic site of the catalyst, and the second nitrogen atom is accessible for the reaction with electrophilic methyl species formed from methanol on acid site of the catalysts. 

H3 Receptor Agonist Activity of Imidazole-methylated Histamine Derivatives... 

L-Idothiofuranoside, ethyl 2-acetamido-2,6-didesoxy-6-nitro-, III, 384 Imidazole, methyl-, III, 117 Immunological properties of dextrans, II, 214... 

Miconazole. Miconazole nitrate [22832-87-7] (Fig. 2), the 1-phenethyl-imidazole derivative first described in 1969, interferes at low doses with the cytochrome P-450 dependent ergosterol biosynthesis in yeasts and fungi. The result is accumulation of C-14 methylated sterols on the one hand and reduction of the ergosterol levels in the membranes on the other hand (12). Analogous to clotrimazole, this leads to a disturbance in the membranes it results in inhibition of ceU repHcation, mycelium development (in C. albicans) and finally, ceU death. High concentrations of miconazole, which may be achieved with topical use, disturb the orientation of phosphoHpids in the membranes, which produces leaks (13). 

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). 

The basicities of the parent azole systems in water are shown in Table 1. When both heteroatoms are nitrogen, the mesomeric effect predominates when the heteroatoms are in the 1,3-positions, whereas the inductive effect predominates when they are in the 1,2-positions. The predominance of the mesomeric effect is illustrated by the pK value of imidazole (82 Z = NH), which is 7.0, whereas that of pyrazole (83 Z = NH) is 2.5 cf. pyridine, 5.2). An fV-methyl group is base-strengthening in imidazole, but base-weakening in pyrazole, probably because of steric hindrance to hydration. When the second heteroatom is oxygen or sulfur the inductive, base-weakening effect increases the pK of thiazole (82 Z = S) is 3.5 and that of isoxazole (83 Z = 0) is 1.3. 

Annular nitrogen atoms can form hydrogen bonds, and if the azole contains an NH group, association occurs. Imidazole (84) shows a cryoscopic molecular weight in benzene 20 times that expected. Its boiling point is 256 °C, which is higher than that of 1-methyl-imidazole (198 °C). 

Despite the weak basicity of isoxazoles, complexes of the parent methyl and phenyl derivatives with numerous metal ions such as copper, zinc, cobalt, etc. have been described (79AHC(25) 147). Many transition metal cations form complexes with Imidazoles the coordination number is four to six (70AHC(12)103). The chemistry of pyrazole complexes has been especially well studied and coordination compounds are known with thlazoles and 1,2,4-triazoles. Tetrazole anions also form good ligands for heavy metals (77AHC(21)323). 

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 general, methyl groups in the 4- and 5-positions of imidazole, oxazole and thiazole do not undergo such deprotonation-mediated reactions, even when the ring is cationic. 

Imidazo[2,l-c][l,2,4]dithiazole-3-thione HNMR,6, 904 <71TL1317> 4/7-Imidazol-5-amine, 4-cyano-4-methyl- H NMR, 5, 16 <83UP40100>... 

Imidazole, 2-bromo-l-methyl-5-nitro-pK 5, 384 B-76M140701, 70AHC(12)103, 80AHC(27)241>... 

Imidazole, 2,4(5)-dibromo-l-methyl-rate constants, 5, 400 (78JCS(P2)865, 74AJC233I) Imidazole, 4,5-dibromo-1-methyl-rate constants, 5, 400 (78JCS(P2)865, 74AJC233I) Imidazole, 4,5-dicyano-pKa, 5, 384 (B-76MI40701, 70AHC(I2)I03, 80AHC(27)24I>... 

Imidazole, 2-fluoro-l-methyl-pK., 5, 384 (B-76MI4070I, 70AHC(I2)I03, 80AHC(27)24I)... 

Imidazole, I-methyl-dipole moment, 5, 351 (7ICHE80I) kinetic data, 6, 21 (73AJCI949)... 

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