Imidazolinone ring

EMazotization of an o-amino-hydrazide at low temperatures leads to the formation of a pyrazole ring (p. 241), but under more drastic conditions, a fused imidazolinone ring may be formed. 

The structural features of imidazolinones important for target site and herbicide activity have been summarized [11-14]. The orientation of the imidazolinone ring ortho to the acid equivalent is critical. Derivatives of the acid equivalent are herbicidally active if they can be metabolized to the acid either in the soil or in the plant. Likewise, tricyclic derivatives such as 4 are pro-herbicides that must be metabolized to the acid-imidazolinone form. 

Although imidazolinones are usually resistant to hydrolysis, oxazolinone rings are often easily opened. In acid-catalyzed reactions of this type, water converts azlactones (181) into a-acylamino-a,/3-uhsaturated acids (182) (77AHC(21)175). 1,3,4-Oxadiazolinones are readily opened by hot water to give hydrazine carboxylic acids which undergo decarboxylation. 

Propargyl alcohol (332) and (328) react readily with isocyanates in the presence of a basic catalyst to give 4-methylene-2-oxazolidinones (334) and 4-methylene-2-imidazolinones (336), respectively (63JOC991). In the absence of sodium methoxide the intermediate methanes (333) and ureas (335) were obtained and on treatment with sodium methoxide underwent ring closure. Moderate to excellent yields were obtained. 

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]. 

In the four-membered rings, the P-lactam moiety is part of the classical penicillin and cephalosporin antibiotics. The most prominent example of a drug with a five-membered ring with one nitrogen atom is Lipitor (see Table 1.1). In the five-membered rings with 2 N atoms, imidazoles are found both in modern agrochemicals, especially the imidazolinones (e.g., Imazapyr), and pharmaceuticals, such as antimycotics (e.g., isoconazole, ketoconazole, and... 

The reaction of lactim ethers with amino acids has been studied in detail.21,23,93 These reactions proceed readily, resulting in the substituted amidino acids. Their cyclization yields fused dihydropyrimi-dinones or imidazolinones (Scheme 13). The cyclization of the aliphatic amidino acids requires drastic conditions, whereas aromatic and heterocyclic amidino acids react under mild conditions, perhaps due to the formation of the new aromatic ring which stabilizes the resulting structure. 

There have also been a few examples of ring expansions involving azetines. One such instance, which follows a pericyclic mechanism, is the thermolysis of 4-cyano-l-t-octyl-3-t-octylamino-2-t-octyliminoazetine (160), producing the 4-amino-5-cyanoimidazole (Scheme 89). Such azetine species have been implicated as intermediates in the photolysis of enaminonitriles to imidazoles (Section 4.08.1.1.1 Scheme 17). In strongly basic medium the azetidinone (161), which possesses a lactam group, is ring expanded to the 4H-imidazolinone (163), probably via the anionic acylic species (162 Scheme 89) <80AHC(27)241>. 

When the dihydro-1,2,4-triazinone (194) is heated at 180 °C under reducing conditions there is rupture of the 1,2-bond followed by ring closure, producing 4,5-diphenyl-imidazolinone (195). Such reductive ring closures of benzotriazine 1-oxides (196) can give benzimidazoles, in particular 2-(4-thiazolyl)benzimidazoles (197) ( thiabendazole ). Similar reactions take place with 1,3,5-triazines. In fact, primary amines cleave the compounds completely with evolution of ammonia and formation of iV.iV -disubstituted formamidines. With suitable primary amines, though, this reaction can be designed to produce imidazolines or benzimidazoles (Scheme 113). 

Mild alkaline treatment of 5-bromo-2 -deoxyuridine 1523 results in a ring contraction of the pyrimidine to form the imidazolinone nucleoside 1524. The a-anomer was isolated after chromatographic purification (Scheme 394) <2005T5081>. 

Eq. 16), which contains a /S-lactam ring as well as an isocyanide group, rearranges in strongly basic medium, probably via the anion 53, to the imidazolinone. ° Azirines have already been mentioned (Section II,E) as intermediates in the transformations of enaminonitriles into imidazoles. 

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