Imidazole /V-oxide

Imidazole /V-oxide substrates may be used in a similar fashion. Initial investigations revealed that the use of palladium acetate in conjunction with an electron deficient 4-fluorophenylphosphine in acetonitrile at 70 °C provides C2 arylation in high yields. With the goal of achieving the same reactivity at or near room temperature it was determined that the use of palladium acetate in conjunction with a Buchwald ligand, catalytic copper bromide and 30 mol% pivalic acid in acetonitrile could also achieve high yields of C2 arylation at 25 °C. As was the case with thiazole V-oxides. if the C2 and C5 positions of the imidazole are blocked C4 arylation may also be achieved in synthetically useful yield (Scheme 15). 

Scheme 15 Imidazole (V-oxides in palladium-catalyzed direct arylation...

Imidazolones, particularly 2-imidazolones, give the corresponding chloro derivatives when heated with phosphoryl chloride, especially with copper(I) chloride as catalyst [76MI1 80AJC1545 90EGP3828208]. The same reagents convert imidazole (V-oxides into 2-chloroimidazoles [75 JCS(P 1)275],... 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

When they have no conjugating substituents 2//-imidazoles absorb in ethanol 240 nm (log e 3). Addition of one or more aryl groups shifts this principal absorption to 261-276 nm (log e 3.71-3.97). No UV data has been reported for 2//-imidazole mono-V-oxides, but the 1,3-dioxides... 

Resistance to oxidative breakdown falls off in the order thiazoles > imidazoles > oxazoles. 2-Substituted thiazoles can be converted into A-oxides," however peracids bring about degradation of imidazoles oxazole /V-oxides can only be prepared by ring synthesis. 

A straightforward conversion of 2-unsubstituted imidazole 3-oxides (66) into the corresponding imidazole-2-thiones (67) is achieved by the reaction with 1 in dichloromethane at rt (eq 28). This sulfur-transfer reaction can be applied to other azole (V oxides with an unsubstituted carbon atom next to the Atoxide position. 

Both nitronium and nitrosonium salts are effective initiators but with quite different results. Thus, propene and nitronium fluoroborate reactto produce the secondary a-nitrocarbenium ion which undergoes Ritter reaction with acetonitrile to yield amide (118). Under similar conditions, nitrosonium fluoroborate leads to heterocyclic products. Intramolecular reaction of the nitroso and nitrilium groups, followed by prototropic shifts, affords the A -hydroxy imidazolium salt (119). This may be either neutralized to produce the /V-oxide or reduced to the imidazole (120 Scheme 55). 

Ru(MpDC)(Im)2 (Im = imidazole), Oj-oxidation to the so-called met form via the outer-sphere process exemplified in eq. 12 (one L = histidine, the other L being unknown) the oxidation rate is faster than that of an axial ligand dissociation, which, for example, is the initial step in formation of Ru(porp)L(CO) via reaction with CO V... 

Electrophilic Trapping of Lithium Species. The deprotonation of arene or heteroarene species followed by quench with electrophiles is a general method for the introduction of functional groups in organic molecules. The arene moiety needs to be electron poor (i.e., thiazoles, imidazoles, pyridine (V-oxides, etc.). Possible electrophiles include sources of halogens, carbonyls, or sulfur. Phenylacetylenes can also be deprotonated with LiO/Bu and quenched with various aldehydes. ... 

Low yields were obtained in the absence of pivalic acid however, employing greater than 30% pivalic acid did not further improve yields or reactivity. Substrates that performed well included C3-substituted benzothiophenes, C2-substituted thiophenes, pyrroles, imidazole, triazole, imidazopyridine, thiazole, and oxazoles, which could be efficiently arylated with aryl bromides. Unfortunately, benzofuran produced low yields (29% with 2-bromotoluene), and furans encountered issues with diarylation, which could be minimized by using more sterically hindered aryl bromides. Arylation of indolizines could be achieved, albeit electron-deficient aryl bromides required longer reaction times (16-24 h). Heterocyclic aryl bromides, such as 3-bromopyridine, could also be employed with thiazole. Problematic aryl halides included cyano, nitro, acetyl, pyridyl functionalities, and N-heterocyclic V-oxides. Other coupling partners, such as aryl tri-flates and aryl chlorides, performed poorly under the reaction conditions. Unsuitable heterocycles included unprotected imidazoles, 2-aminothiazole, isoxazole, benzothiazole, and benzoxa-zole, which failed to produce arylated products. 

Determination of electrochemical oxidation potentials and electrochemical reduction of 13 p-phosphorylated acyclic nitrones shows that phosphorylated compounds have a clear anodic shift of potentials of both, oxidation (Ep 1.40 to 2.00 V versus SCE in CH3CN) and reduction (Ep—0.94 to —2.06 V). This is caused by a strong electron-acceptor influence of the diethoxyphosphoryl group (430). In contrast, a reversible one-electron oxidation of azulene nitrones (233) (Scheme 2.80) occurs 0.6 V below the Ep potential of PBN, that is at the value one observes the oxidation of AH -imidazole-1,3-dioxides (219) (428, 429). In other words, the corresponding RC (234) is 14 kcal more stable than the RC of PBN. Although the EPR spectrum of RC (234) was not recorded, RC (236) from dinitrone (235) turned out to be rather stable and gave an EPR spectrum (170). 

---