Imidazolone syntheses

Imidazolone synthesis, 291 Imidoline, 259 Imipramine, 420 Indapamide, 349 Indazole synthesis, 350 Indoles, as starting material for benzodiazepines, 405 Indomethacin, 345 Indoramin, 344 Incfoxoie, 254, 340 Inflammation, 63 Influenza A, 18 Inhibition,... 

An efficient solventless synthesis of imidazolones via the Knoevenagel reaction using microwave irradiation has appeared recently in Green Chemistry [76] (Scheme 8.52). 

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). 

The synthesis of the coupling component 5-acetoacetylaminobenzimidazolone (25) corresponds to the preparation of acetoacetarylides (Sec. 2.1.2) from 5-aminobenz-imidazolone by reaction with diketene or acetoacetic ester ... 

Pagoria and co-workers " " also reported the synthesis of (113) (K-56, TNABN) and the trinitrated derivative, 2,5,7-trinitro-2,5,7,9-tetraazabicyclo[4.3.0]nonane-8-one (115) (HK-56). Their route to the bicycle (112) was via bromination of l,3-diacetyl-2-imidazolone, followed by reaction with ethylenedinitramine and nitrolysis of the acetyl groups. 

Scheme 31 Catalyst-free three-component synthesis of functionalized imidazolones...

Amino acids " " and aminobenzoic acids " " react as nitrogen nucleophiles to effect ring opening of unsaturated 5(4//)-oxazolones. Cyclization of the intermediate acylamino amide has opened the way for the synthesis of new series of imidazolones that now incorporate a carboxylic acid moiety into the N-1 substituent. These compounds are readily further elaborated into derivatives with diverse biological activity. 

The synthesis and antimicrobial activity of new l-aryl-4-arylmethylene-2-phenyl-5(4//)-imidazolones 818, obtained from reaction of 4-arylmethylene-2-phenyl-... 

Similarly, 4-(furan-2-ylmethylene)-2-phenyl-1 -substituted-5(477)-imidazolones 820, evaluated as antibacterial and antifungal agents, have been synthesized from the 4-(furan-2-yhnethylene)-2-phenyl-5(4//)-oxazolone 819 (Scheme 7.253). ° Using 4-arylmethylene-2-phenyl-5(4//)-oxazolones as substrates and 2-amino-5-methyl-l,3,4-thiadiazoles as nucleophiles the synthesis of the corresponding... 

Fig. 4. Solid-phase synthesis of an indolepyridoimidazole library and an imidazo-imidazolone hbrary from resin-bound acylated dipeptides.

Lerestif, J.M., Perrocheau, J., Tonnard, F., Bazureau, J.P., and Hamelin, J. 1995. 1,3-Dipolar cycloaddition of imidate ylides on imino-alcohols Synthesis of new imidazolones using solvent free conditions. Tetrahedron, 51 6757-74. 

Diaminomaleonitrile derivatives 1112 are useful synthons for the synthesis of imidazoles (see CHEC(1984) and CHEC-II(1996)). For example, imidazolone 1115 is obtained from the reaction of 1,2-diaminomaleonitrile with isocyanate 1113 via the intermediate A -[(Z)-2-amino-l,2-dicycanovinylcarbamoyl]-/>-toluenesulfonamide 1114 (Scheme 269) <2001JHC939>. 

The cycHc urea moiety provides structural rigidity as well as hydrogen-bonding possibihties similar to those of the imidazoles described above. The corresponding 2-imidazolones have been prepared on a soHd phase by tandem aminoacylation of a resin-bound allylic amine with an isocyanate followed by intramolecular Michael addition [73]. However, due to the paucity of data presented on the characterized compounds and the brief experimental procedure, this synthesis is not discussed in detail. Access to cyclic ureas or thioureas has also been obtained by reaction with carbonyl- or thiocarbonyldiimidazole through a cyclo-release mechanism [74—76]. 1,3-Dihydroimidazolones have been obtained by treatment of ureido acetals with TFA and subsequent conversion in an intramolecular cyclization via an N-acyliminium ion [77]. 

The most common examples utilize the old Marckwald synthesis in which an a-aminocarbonyl species (or equivalent aminonitrile) reacts with cyanates, thiocyanates, cyanamide, etc. to give 2-imidazolones, 2-imidazolethiones, 2-aminoimidazoles, or reduced versions in cases where aro-matization is not favored. Often oxidation or dehydrogenation will accomplish the aromatization. 

A number of examples of imidazole synthesis from azirines and aziridines have been included under other classifications (see Sections 3.02.8.1.l(iii) and 3.02.8.1.2(i),(ii)). 2/f-Azirines are intermediates in the rearrangement of oximino p-toluenesulfonates to aminoketones in the presence of bases, and with 2-acylphenols these azirines form imidazolones. 4//-Imidazoles (244) are formed when a 2-amino-3,3-dimethylazirine reacts with an acetamide (Scheme 181) <90CHE719>. 

Metal-mediated approaches to the synthesis of imidazoles have been reported. PaUadium(ll)-catalyzed intermolecular 1,2-diamination of conjugated dienes with ureas led to 4-alk enyl-2-imidazolones in good yields rmder mild conditions <05JA7308>. Palladium-catalyzed cyclization of O-pentafluorobenzoylamidoximes 74 furnished l-benzyl-2-substituted-4-methylimidazoles 75 <050L609>. Direct copper(I)-chloride mediated reaction of nitriles 76 with a-amino acetals 77 followed by acidic reaction led to a variety of 2-substituted imidazoles 78 <05TL8369>. 

Shaw and McDowell41 have prepared imidazolone derivatives by cyclization of a-acylamino amides. In a variation of this reaction the azlactone (30) was gradually converted to the hydroxamic acid (31) by methanolic hydroxylamine. Sodium methoxide and hydroxylamine readily gave the acyclic hydroxamic acid (32) which could be cyclized to 31 by dilute acid. Benzyloxyurea has been used in the synthesis of pyrimidine hydroxamic acids (33) by reaction42 with /3-diketones followed by catalytic hydrogenation of the benzyl group. Protection... 

A synthesis of 3,5-dioxo-2/f,3i/-pyrrolo[l,2-c]imidazoles (132) has been developed by reaction between the imidazolones (131) and anhydrides in NaH/DMF (Scheme 25) <9lJOC858,92JMC1267>. 

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