Imidazolone formation

Knochel s method provided the pentameric peptide 224. Hydrogenation followed by treatment of the resulting amino acid with EDC and HOBt afforded macrocycle 225. Hydrolysis of methyl ester 225, and imidazolone formation via the acid chloride, followed by Boc deprotection provided kapakahine F (219) in significant quantity. Final coupling of 219 with Boc-Phe-OH followed by Boc removal afforded kapakahine B (218) (Scheme 40). 

Dehydration converting the imidazolone ring to imidazolinone seems to be sensitive to the aromatic nature of residue 66 [61, 62]. This step is thought to lead to the formation of an enolate intermediate, which can be trapped by reverse anaerobic chemical reduction of the mature chromophore using dithionite and other reducing agents [63]. 

Comparison of this reaction with that performed using classical heating shows an acceleration of the 1,3-dipolar cycloaddition upon irradiation and yield enhancements for the synthesis of imidazolones 122. These advantages occur by virtue of diminished formation of the byproduct 125 (see Scheme 9.37). 

Moreover, the oxidation of methional to ethylene has been proposed (Beauchamp and Fridovich 1970 Biaglow et al. 1997), and the formation of allantoin (Grootveld and Halliwell 1987 Halliwell et al. 1988) from uric acid as well as the imidazolone derivative from histamine (Ching et al. 1995) have been suggested as an index of OH action in vivo (Halliwell et al. 1988). 

Velikyan I, Acharya S, Trifonova A, Foldesi A, Chattopadhyaya J (2001) The pffas of 2 -hydroxyl group in nudeosides and nucleotides. J Am Chem Soc 123 2893-2894 Veltwisch D, Asmus K-D (1982) On the reaction of methyl and phenyl radicals with p-benzoquinone in aqueous solution. J Chem Soc Perkin Trans 2 1147-1152 Vialas C, Pratviel G, Claparols C, Meunier B (1998) Efficient oxidation of 2 -deoxyguanosine by Mn-TMPyP/KHSOs to imidazolone dlz without formation of 8-oxo-dG. J Am Chem Soc 120 11548-11553... 

Asaro, M. F. Nakayama, I. Wilson, R. B. Formation of sterically hindered primary vicinal diamines from vicinal and geminal dinitro compounds. /. Org. Chem. 1992, 57, 778-782. Rodriguez, H. Marquez, A. Chuaqui, C. A. Gomez, B. Oxidation of mesoionic oxazolones by oxygen. Tetrahedron 1991, 47, 5681-5688. Heras, M. Ventura, M. Linden, A. Villal-gordo, J. M. Reaction of a-iminomethylene amino esters with mono- and bidentate nucleophiles a straightforward route to 2-amino-lH-5-imidazolones. Tetrahedron 2001, 57, 4371—4388. 

Although these transformations or oxazolinones and thiazolinones can be extended to imidazolones such as (271 Scheme 119), which also proceed through the acylamidrazone intermediate (272), the alkaline reagent (0.2% sodium hydroxide) may cause partial hydrolysis of the amide with the formation of acid (273 2%) or the amide (274) (69AC(R)434). 

Unlike formamidine, acetamidine and benzamidine react with both aromatic and aliphatic a-hydroxyketones to give imidazoles exclusively. It has been suggested that aryl groups favour the enolic form (2) of the tautomeric mixture, resulting in the formation of oxazoles as major products. Aliphatic groups favour the keto form (1), from which imidazoles are derived. That amidines more complex than formamidine favour imidazole formation may be a consequence of steric hindrance to reaction of the enolic hydroxy groups with the amidine carbon in (2). The general reaction has been used to prepare such compounds as 4,5-dipropyl imidazole (25% yield from tris(formylamino)-methane and 5-hydroxyoctan-4-one), and a variety of 2-imidazolones and 2-aminoimidazoles [8]. The fact that oxazoles can be converted into imidazoles with some ease extends the applicability of this reaction. 

One of the notable features of this rearrangement is the exclusive formation of 5-imidazolones 315 rather than the isomeric 4-imidazolones (Scheme 74). These results were attributed to two causes. Sterically, the 5-imidazolone is less crowded than the isomeric 4-imidazolone since the spirocyclopentyl ring is further away from the... 

Like other heterocyclic iV-oxides, imidazole 3-oxides 1063 react with AC2O to give the corresponding imidazolones 1064 and 1065 (Scheme 257). TMSCN transforms 1063 into imidazole 2-carbonitriles 1066, whereas alkyl thiones convert 1063 to 1067 <2000HCA728, 1998HCA1585, 2002AGE2290>. The 2-aminoimidazoles 1068, formed from the reactions with either isocyanate or isothiocyanate, react further with isocyanates to form ureas but are inert toward thiourea formation. In contrast to nonaromatic imidazole A -oxides (nitrones), oxides 1063 react with DMAD to form butanedioates 1069, rather than the (putative) [3-1-2] adduct <2000T5405>. 

A protocol involving the intermolecular cyclization between acetals and ureas has been developed to synthesize imidazolones on solid support. Reaction of polymer-bound glycerol 1148 with bromoacetaldehyde diethyl acetal gives the cyclic acetal bromide 1149. Amination followed by urea formation affords the resin-bound urea acetals 1150. The aldehydes released from the resin upon treatment with TFA immediately cyclize to give 2-imidazolones 1151 in good yields and purity (Scheme 279) <2002TL4571>. 

There are a number of examples also of the formation of 2-imidazolones and 2-benzimidazolones from reaction of 2-halogeno salts with dilute sodium hydroxide <81AG(E)612, 82CHE830>. With... 

Generally the yields of 2-aminooxazoles (37) are moderate to good with 2-amino-4,5-diphenyloxazole maximum yield of 91% has been obtained. Poor yields of the oxazoles are often accompanied by the formation of imidazoles and 2-imidazolones as by-products.104... 

Within double-stranded oligonucleotides, the imidazolone derivative was not the major product. The HPLC peak detected at 260 nm (Fig. 29A) and containing this lesion (in-line ESI-MS data) eluted at a retention time of 40.1 min. This product incorporated one oxygen atom from labeled water and the mechanism of its formation could be attributed to a nucleophilic attack of a water molecule at the former C5 of guanine 253). 

Fig. 31. Proposed mechanism for the formation of dehydro-guanidinohydantoin and imidazolone from intermediate 30 accounting for the labeling data. Numbering of carbon atoms corresponds to that of guanine.

Heating of 3-amino-2-picolinic acid azide in toluene for a short duration gave IP-2-one in 50% yield, whereas the thermolysis of 2-aminonicotinoyl azide in xylene led to the formation of the same imidazolone but in 90% yield. This imidazolone is also formed in a relatively poor yield ( 38%) on pyrolysis (210-220 °Q of both 3-aminopicolinoyl hydroxamic acid and its isomer, 2-aminonicotinoyl hydroxamic acid. In the latter case 2-aminonicotinic acid (59JCS3157) is formed as a by-product in 19% yield. 

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