Synthesis imidazolinones

The inhibitors of amino acid synthesis, sulfonylureas, imidazolinones, and glyphosate, were first recognized as general growth inhibitors that prevent mitotic entry (188,189). Whatever the mode of action, herbicides that inhibit amino acid synthesis also cause a rapid inhibition of cell growth, usually through inhibition of mitotic entry. 

Imidazolin-2-one, 1,5-diphenyl-4-aryl-synthesis, 5, 492 4-Imidazolin-2-one, 1-hydroxy-synthesis, 5, 474—475 4-Imidazolin-2-one, l-methyl-3-phenyl- C NMR, 5, 355 Imidazolinones acylation, 5, 424, 443 alkylation, 5, 443 developers... 

The synthesis of symmetrically and unsymmetrically substituted J ,J -diarylimidazolin-2-ones by copper-catalyzed arylamidation under microwave-assisted and conventional conditions was studied <07S1403>. Palladium-catalyzed direct functionalization of imidazolinone with aryl halides has been reported <07JA7768>. 

Imazapyr/ 2-[4,5-dihydro-4-methyl-4-(l-methyl ethyl)-5-oxo-lH-imidazol-2-yl]-3-pyridi necarboxylic acid Imidazolinones Amino acid synthesis inhibitor, nonselective Noncrop areas, railroad tracks, plantations 11-8... 

Nitrogen Heterocycles.- Reactions of iminophosphoranes have been used to prepare a wide range of heterocycles. Examples of compounds prepared by intramolecular aza-Wittig reactions include 3,4-dihydroquinazolines (191) and quinazolines (192), quinazoline derivatives (e.g. 193),pyrrolo( 1,2-a)quinoxalines (194), indolo[3,2-clquinolines (195), and indolo[l,2-c]quinazolines (196),"8 imidazolinones (197),"9 quinazolinones (198),"9, 120 pyrido[2,3-d]pyrimidine derivatives (199), 21 and 4,5-dihydropyrazolo(3,4-d]pyrimidine derivatives (200). 22 Tributyl(cyclohepta-1,3,5-trienylimino)phosphorane (201), prepared by thermal isomerization of the 2,4,6-derivative, reacts with a,p-unsaturated ketones to give 9H-cyclohepta[b]pyridine derivatives (202). 23 a synthesis of (2,4)pyridinophanes (204) by the reaction of N-vinyliminophosphoranes (203) with a,P-unsaturated ketones has been reported. 24... 

The synthesis and herbicidal activities of various imidazolinthiones, in particular the thiono isosteres of imazapyr, imazethapyr and imazamethabenz are discussed. In the synthesis area it is shown that the imidazolinthione ring functions as an ortho-directing group in aromatic lithiations. In the biological activity area it is shown that replacement of the imidazolinone carbonyl with a thio-carbonyl results in changes in weed toxicity and crop selectivity. 

The original Lonza synthesis [1, 2] of (d)-(+)-biotin 1 (outlined in Fig. 1) was designed around the critical diastereoselective hydrogenation of the tetrasubstituted double bond in imidazolinone 2 to the desired 3aS,6aR isomer 3. This strategy was a natural consequence of the experience gained with an analogous diastereoselective hydrogenation in the synthesis of an intermediate for the Merck antibiotic thienamycine (see Fig. 2). 

Lolium biotypes exist which have resistance to the sulfonylurea herbicides chlorsulfuron and metsulfuron methyl (4). The biotype used in the studies presented here is resistant to both these sulfonylurea herbicides. Sulfonylurea herbicides inhibit the chloroplastic enzyme acetolactate synthase (ALS), also known as acetohydroxyacid synthase (AHAS) (16). Inhibition of this enzyme results in disruption of the synthesis of the branched-chain amino acids valine and isoleucine (161. The imidazolinone herbicides also inhibit ALS Q2). In some species auxins can protect against chlorsulfuron inhibition (S. Frear, USDA North Dakota, personal communication) the mechanistic basis for this protection is not known. We have measured the ALS activity in the resistant and susceptible Lolium and have also checked for any induction of ALS activity following treatment with the sulfonylurea herbicide chlorsulfuron. 

Identification of the mode of action of the imidazolinones occurred while resistant cell lines were being isolated. Imidazolinones inhibit acetohydroxyacid synthase (AHAS EC 4.1.3.18), the first enzyme in the pathway of branched chain amino acid synthesis (8). Imidazolinone-resistant cell lines provide proof that inhibition of AHAS is the site of action of the imidazolinones AHAS activities in extracts from resistant corn cell lines are highly resistant to inhibition by imidazolinone herbicides (7). 

The L-isomer of 111 (R1 = R2 = H) has been obtained by enzymatic degradation of an appropriate DL-derivative.474,475 In an interesting asymmetric synthesis, the imidazolinone 112 [L = (SJ-l-phenylethyl] was... 

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). 

Another recent asymmetric amino acid synthesis involves the reaction of a methyl 2-isocyanoalkanoate (5) with I in the presence of -butyllithium or potassium t-butoxide to form the metalated imidazolinones 6 in situ. Alkylation of 6 results in chiral 4,4-disubstituted imidazolinones (7) often in optical yields of 90-1007o. The highest optical yields are obtained when R has a higher priority than R. In this case 7 has the (R)-configuration. Reversal of the priority results in the (S)-configuration. Hydrolysis of 7 to the chiral amino acid 8 requires rather drastic conditions and is best conducted with base. This method was reported for the synthesis of twenty 2-imidazoline-5-ones of type 7. ... 

With the invention of the aceto-hydoxy-add synthesis inhibitors (AHAS) the dominance of herbiddes that ad as photosynthesis inhibitors was dramatically broken - as it was also by the development of genetically modified herbicide tolerant crops. These especially important areas of research and development, from the 1990s up to now, are exemplified in Chapters 3 and 7. The development of 12 new sulfonyl urea herbicides launched since 1995 and the invention of four development compounds of the same chemical class, after the introduction to the market of twenty compounds already between 1980 and 1995, refleds the importance of this biochemical mode of adion for the herbicide market as well as the different chemistries found to be active at this target, such as imidazolinones, triazolo-pyrimidines, pyrimidinyl-carboxylates, and sulfonylaminocarbonyl-triazolinones. 

Synthesis methodology for numerous imidazolinones is described in the patent literature [2-6]. Figure 2.3.1(A) shows a simple one-step method [7j. 

Los, M. Synthesis and Biology of the Imidazolinone Herbicides, in Pesticide Science and Biotechnology, Greenhalgh, R., Roberts, T. R. (Eds.), Blackwell Scientific Publications, Oxford, 1987. 

Dihydropyrano[2,3-b]pyridylimidazolinones and related compounds represent a new series in the imidazolinone herbicide family developed by American Cyanamid Company. The synthesis of the parent compound was accomplished by a novel enaminone-directed cyclization to the pyrano ring in the key step. These compounds showed excellent herbicidal activity with soybean selectivity. 

Final synthesis of the imidazolinone was accomplished by the usual four-step sequence as described below. 

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