Imidazol pyridines, formation

Without additives, radical formation is the main reaction in the manganese-catalyzed oxidation of alkenes and epoxide yields are poor. The heterolytic peroxide-bond-cleavage and therefore epoxide formation can be favored by using nitrogen heterocycles as cocatalysts (imidazoles, pyridines , tertiary amine Af-oxides ) acting as bases or as axial ligands on the metal catalyst. With the Mn-salen complex Mn-[AI,AI -ethylenebis(5,5 -dinitrosalicylideneaminato)], and in the presence of imidazole as cocatalyst and TBHP as oxidant, various alkenes could be epoxidized with yields between 6% and 90% (in some cases ionol was employed as additive), whereby the yields based on the amount of TBHP consumed were low (10-15%). Sterically hindered additives like 2,6-di-f-butylpyridine did not promote the epoxidation. 

Much has been learned from synthetic complexes (Section 17-E-7). The requirements to mimic oxyhemoglobin are the formation of a 5-coordinate heme precursor having a proximal base (imidazol, pyridine, or other) and hindering pathways that would lead to irreversible formation of /i-peroxo dimers. The lifetime of the working models is increased by exclusion of acidic protons and nucleophiles from the 02 binding site and working at low temperatures. 

From these structural and chemical features considered necessary to mimic oxyhemoglobin or oxymyoglobin, there are at least two minimum requirements that any realistic models must satisfy (1) formation of a five-coordinate heme precursor having a proximal base (imidazole, pyridine and so on) and (2) limitation of pathways that lead to irreversible oxidation. 

In the olefin epoxidation, the mechanistic scheme commonly proposed for the oxygen-transfer reaction consists of a two-step catalytic cycle (Pig. 21) 123). In the first step, an oxygen atom is transferred from the primary oxidant to the Mn -salen catalyst, which in the second step carries the activated oxygen to the olefinic double bond. The main problem in Mn-salen catalyzed epoxidation with H2O2 was the formation of HO radicals by the homolytic cleavage of the weak 0-0 bond, leading to indiscriminate oxidation 124). Addition of Lewis bases, such as imidazole, pyridine, or... 

Herrmann, W. A. Koecher, C. Goossen, L. J. Artus, G. R. J. Chem. Eur. J. 1996,2,1627. A combined synthesis involving the formation of the halide salt and an in situ anion metathesis with a sodium salt was also developed, but requests very long reaction time (typically two weeks) Wasserscheid, R HUgers, C. Boesmann, A. Single step preparation of ionic fluids by alkylation of amines, phosphines, imidazoles, pyridines, triazoles, and pyrazoles with alkyl halides followed by ion exchange. Eur. Rat. AppL 1182197, 2002 Branco, L. C. Rosa, J. N. Moura Ramos, J. J. Afonso, C. A. M. Chem. Eur. J. 2002, 8,3671. 

Necessary conditions for synthetic models to mimic oxyhemoglobins are formation of a five-coordinate heme precursor with a proximal base (e.g., imidazole, pyridine), prevention of p-peroxo/p-oxo (M-02-M/M-0-M) dimer formation upon oxygenation (i.e., reversible oxygenation), and exclusion of protons and nucleophiles. Model systems should be easily modified and allow probing of distal and proximal influences. Tetraphenyl-porphyrins (TPP) serve as the basis of numerous model complexes, because they are less susceptible to oxidation... 

Benzidine-like rearrangements are reported on acid treatment of suitable imidazoles , pyridine and thiazole hydrazocompounds , but not ferrocene derivatives. Related, probably intramolecular, rearrangements of/>-quinamines and 0,iV-diarylhydroxylamines , (reactions 106 and 107) have been arbitrarily assigned w-bond mechanisms, whereas reactions (108) and (109) are probably inter-molecular, although the observed formation of cross-over products counts for litde . ... 

Another example of imidazole ring formation in aqueous medium is reported by Proenca and Costa [65]. A one-pot condensation/cyclization reaction involving l-(cyanomethyl)pyridinimn chloride 94 and salicylaldehyde 95 in aqueous sodimn carbonate solution leads to the formation of chromeno-imidazo[l,2-a]pyridine scaffold 96 with 47-71% yield. The reaction is general to electron-donating groups (EDG) and electron-withdrawing groups (EWG). A representative example is shown in Scheme 31. 

Resorcinol or hydroquinone production from m- or -diisopropylben2ene [100-18-5] is realized in two steps, air oxidation and cleavage, as shown above. Air oxidation to obtain the dihydroperoxide (DHP) coproduces the corresponding hydroxyhydroperoxide (HHP) and dicarbinol (DC). This formation of alcohols is inherent to the autooxidation process itself and the amounts increase as DIPB conversion increases. Generally, this oxidation is carried out at 90—100°C in aqueous sodium hydroxide with eventually, in addition, organic bases (pyridine, imidazole, citrate, or oxalate) (8) as well as cobalt or copper salts (9). 

Formation of a central pyridine ring can also be effected by reaction of 2-(pyrrol-2-yl)imidazoles with ethyl bromoacetate <1999TL8157>. Kandeel et al. also synthesized angular systems in this manner from the thioxo-pyranopyrazole precursor <2002H(57)1121>. 

This alkylation reaction can be applied to intramolecular alkylation affording cyclic products, as shown in Equations (19)-(21). The reaction of 2-vinylpyridines with 1,5- or 1,6-dienes results in the formation of five- or six-membered carbocycles with good efficiency.20,20a,20b In addition to pyridine functionality, oxozole and imidazole rings can be applied to this intramolecular cyclization. When the reaction is conducted in the presence of a monodentate chiral ferrocenylphosphine and [RhCl(coe)2]2, enantiomerically enriched carbocycles are obtained. A similar type of intramolecular cyclization is applied to TV-heterocycles. The microwave irradiation strongly... 

Kinetic studies on complex formation reactions of the tripodal tetra-mine complex [Co(Me6tren)(H20)]2+ with pyridine, 4-methylpyridine, and imidazole yielded activation parameters AH1, and AS. Activation parameters and dependences of rate constants on incoming ligand concentration indicated that the formation mechanism ranged from dissociative for the weaker and bulkier incoming ligands (py, 4-Mepy) to associative for the more basic and less bulky imidazole 2-methylimida-zole occupies an intermediate position (280). 

More recently, a new and straightforward one-pot approach was reported by Bu et al. <2003JOC5415>. This reaction involves the cyclocondensation of l,2-dipyridin-2-yl-ethane-l,2-dione 120 and arylaldehydes, in the presence of ammonium acetate. Imidazo[l,5- ]pyridines 121 were obtained in reasonable yields, but competitive formation of imidazoles 122 was observed. The amount of ammonium acetate used in this reaction was also shown to strongly influence the yield of the cyclization (Scheme 38). 

---