Imidazolinone formation

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]. 

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. 

Certain quinoxaline (V-oxides (191), too, are converted into 1-acetyl-3-aroylbenz-imidazolinones (193) when they are heated in acetic anhydride. The reaction proceeds by an initial acetylation at N-3, and this is succeeded by formation and rearrangement of an intermediate oxaziridine (192 Scheme 111). Apart from their involvement in other reactions discussed earlier, such intermediates have also been invoked to explain the formation of 1,3-dibenzoylbenzimidazolinone (70%) when quinoxaline 1,3-dioxide is exposed to sunlight (74CRV279). 

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). 

Fig. 17 Bronsted acid-induced LLC phase formation of a chiral imidazolinone monomer as means of generating nanoporous, solid-state, chiral Diels-Alder catalysts. Partially reproduced with permission from [120]. 2005 by the American Chemical Society...

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. 

For example, glyphosate inhibits the enzyme, EPSP (5-enolpyruvylshikimate 3-phosphate) synthase, that catalyzes a step in the synthesis of the aromatic amino acids. Similarly, both the imidazolinones and sulfonylureas inhibit acetolactate synthase (ALS), the enzyme that catalyzes the first step in the formation of branched-chain amino acids (11). Triazine herbicides act by binding to a specific protein in the thylakoid membranes of the chloroplasts, preventing the flow of electrons and inhibiting photosynthesis (12). 

Inhibitors of Acetolactate Synthase (ALS/AHAS) The enzyme acetolactate synthase (ALS) plays in plants an essential role in branched-chain amino acid biosynthesis. In the pathway leading to valine and leucine, ALS catalyzes the formation of 2-acetolactate from two pyruvate molecules, and in the pathway to isoleucine the formation of 2-acetohydroxybutyrate from 2-ketobutyrate and pyruvate. Due to this double function the enzyme is also called with a more general term aceto-hydroxyacid synthase. ALS is inhibited by several groups of herbicides, mainly the sulfonylureas (SUs), imidazolinones (IMIs), triazolopyrimidines (TPs), pyrimidinylthiobenzoates(PTBs) and sulfonylaminocarbonyltriazolinone (SCTs) (see Chapter 2.1, M. E. Thompson). 

Besides the formation of oxazole derivatives, Schollkopf and the others have successfully extended the a-alkali metalated isocyanides to the formation of the chain-extended primary amines, 2-oxazolines, 2-thiazoline-4-carboxylic esters," 2-imidazolines, 2-pyrrolines and pyrroles, thiazoles, 2-imidazolin-5-ones," 2-imidazolinones," etc. For example, a simple reaction between lithiomethyl isocyanide with two equivalents of piperonal followed by acetylation of the intermediate with acetic anhydride affords the corresponding oxazoline. ... 

Cyclization of a series of aryl-substituted 2-(Ai-benzoyl-A -methyl)aminoalkan-amides (107 X = H, Cl, NO2, OMe, CN) in alkaline solution led to the formation of the corresponding imidazolinones (108) the Hammett reaction constant was found to be /o = 1.4, consistent with a mechanism involving initial deprotonation of the amide group, followed by intramolecular attack of the benzoyl group by the amide ion. For the compound (109) in which the isopropyl group of (107) was replaced with a 4-nitrophenyl group, the reaction observed (Scheme 19) was more complex. This was due to the lability of the first-formed imidazolinone (110), which yielded with hydroxide ion a moderately stable intermediate (113)... 

Scheme 11 Formation of imidazolinone groups by cyclodehydration of dipeptide-like moieties formed during amine-oxazolinone chain coupling.

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