Imidazole Michael addition

Such groups a to a pyridine-like nitrogen atom are expected to undergo Michael additions. Examples are known in the imidazole series. 

Imidazole, 2-ethyl-1 -(o-nitrophenyl)-cyclization, S, 431 Imidazole, 4-ethyl-2-phenyl-oxidation, S, 405 Imidazole, ethynyl-Michael addition, S, 437 Imidazole, 4-ethynyl-2-phenyl-synthesis, S, 494 Imidazole, 1-formyl-reactions, S, 452 Imidazole, 2-formyl-mass spectra, S, 360 Imidazole, 4-formyl-synthesis, S, 475-476 Imidazole, 2-formyl-1,5-dimethyl-mass spectra, S, 360 3-oxide... 

In 2002, Leadbeater and Torenius reported the base-catalyzed Michael addition of methyl acrylate to imidazole using ionic liquid-doped toluene as a reaction medium (Scheme 6.133 a) [190], A 75% product yield was obtained after 5 min of microwave irradiation at 200 °C employing equimolar amounts of Michael acceptor/donor and triethylamine base. As for the Diels-Alder reaction studied by the same group (see Scheme 6.91), l-(2-propyl)-3-methylimidazolium hexafluorophosphate (pmimPF6) was the ionic liquid utilized (see Table 4.3). Related microwave-promoted Michael additions studied by Jennings and coworkers involving indoles as heterocyclic amines are shown in Schemes 6.133 b [230] and 6.133 c [268], Here, either lithium bis(trimethylsilyl)amide (LiHMDS) or potassium tert-butoxide (KOtBu) was em-... 

Imidazole has been condensed via a 1,4 Michael addition with ethyl acrylate by use of basic clays (Li+ and Cs+ montmorillonites) under solvent-free conditions with microwave irradiation [77] (Eq. 24). 

The microwave activation of Michael additions in the preparation of N-substituted imidazoles afforded excellent yields in very short reaction times under mild reaction conditions, Scheme 10.9. Basic clays (Li+, Cs+) exchanged montmorillonites were found to be very active and selective catalysts for the Michael addition of imidazole and ethyl acrylate [54]. 

Scheme 10.9 Michael addition of imidazole with ethyl acrylate.

Some Michael additions of unsaturated reagents to imidazoles involve the neutral species of the heterocycles, but others may be reactions of the anion. Fluoride ion catalyzed addition of 2-methyl-4-nitroimidazole (113) to a suitable Michael acceptor gives almost quantitative yields of the 1-substituted 4-nitroisomers (114) (90JOC3702,91JCR(S)35o). 

Imidazole, l,2,5-trimethyl-4-nitro-mass spectra, 5, 359 Imidazole, 1-trimethylsilyl-reactions, 5, 454 with acid chlorides, 5, 391 Imidazole, 1-trimethylstannyl-reactions, 5, 454 Imidazole, 2,4,5-trinitro-reactions, 5, 98 synthesis, 5, 395 Imidazole, 1,2,4-triphenyl-UV spectra, 5, 356 Imidazole, 1,2,5-triphenyl-UV spectra, 5, 356 Imidazole, 2,4,5-triphenyl-chemiluminescence, 5, 381, 406 irradiation, 5, 433 oxidation, 5, 376, 406 photochemical addition reactions, 5, 421 synthesis, 5, 467, 483 UV spectra, 5, 356, 357 Imidazole, 1-trityl-rearrangement, 5, 377 Imidazole, vinyl-Michael addition, 5, 437 polymers, 1, 281 Imidazole, 1-vinyl-reactions, 5, 450 thermal rearrangement, 5, 450 Imidazole, 2-vinyl-oxidation, 5, 437 Imidazole, l-(D-xylofuranosyl)-synthesis, 5, 491 277-Imidazole, 2,2-dialkyl-rearrangement, 5, 422 277-Imidazole, 4,5-dicyano-2,2-dimethyl-synthesis, 5, 472... 

Enantioselective Michael additions of pyrroles to a,(3-unsaluralcd 2-acyl imidazoles were accomplished by Sc(III)triflate-bis(oxazolinyl)pyridine com-... 

Vinyl and ethynyl groups attached to an imidazole ring can be catalytically reduced to the saturated (or less unsaturated) species and cleaved by oxidation. The corresponding 4-carbaldehyde is formed in 71% yield when l-methyl-2,5-diphenyl-4-styrylimidazole is oxidized with osmium tetroxide. However, they may not react like aliphatic alkenes and alkynes not all addition reactions occur normally, Michael additions are known, and the compounds can act as dienophiles in DielsAlder reactions (e.g., Scheme 132). 

Imidazol 4,5-Diethoxycarbonyl-l-propyl- IV/la, 746 Kohlensaure -[l-(3,5-dimethoxy-phenyl)-1 -methyl-ethylester]-hydrazid XV/1, 151 Propan 2-(3,4-Dimethoxy-phenyl)-3-methylamino-1-nitro- E16d, 233 (Michael-Addition)... 

Regioselective Michael addition of imidazole to levoglucosenone 475 is effectively catalyzed by cathodic electrolysis. The electrochemical conditions are milder and provide higher yields as compared to the base-catalyzed reactions (Scheme 110) <1996JOC8786>. 

Heteroarylamines, for example 1195, react with (dimethylamino)propenoate 1196 to yield an imidazolecarboxylate 1199. The imidazole ring is formed via the intermediate diaminoalkenoate 1197, which undergoes an intramolecular Michael addition followed by a retro-aldol-like reaction (Scheme 294) <1998JHC1527>. Similarly, 4-dimethyl-amino-2-aza-l,3-dienes 1200, serving as y-dielectrophiles, condense with amines or hydrazines neat at 70 °C to form A -substituted imidazole-4-carboxylates 1201 in 60-75% yields (Scheme 294) <1999TL8097>. 

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]. 

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