4.4- Dimethyl-4//-imidazole, rearrangement

Fig. 11) would likely proceed by different mechanisms. Protonation of the diol (IV, Fig. 12) derived from theobromine would lead to ring opening at the C6— Cs position giving an imidazole isocyanate (XVI, Fig. 12). This could readily form XVII which after hydrolysis and loss of C02 would give dimethyl-allantoin (XVIII). On the other hand, the uric acid diol derived from caffeine (X, Fig. 12) cannot fragment by this mechanism. Accordingly, either or both of the processes could Occur via the form of the diol hydrated at the C6 carbonyl group (XIX, Fig. 12) which could readily lose C02 to give XX followed by rearrangement to trimethylallantoin (XXI).

A similar type of transmetalation was also seen with l,2-dimethyl-5-trimethylstannylimidazole, which gave the 5-lithio derivative at -100°C, but rearranged to the 2-lithiomethyl derivative at higher temperatures [83JCS(P1)271]. However, transmetalation does not occur with Grignard reagents and 5-substituted imidazoles can be successfully prepared via this route (Scheme 49) (81 Mil 82OPP409). 

Sheradsky has found that the hydroxyl function of a ketoxime such as acetophenone oxime can be made to react with DMAD when the reaction is carried out in methanol with a basic catalyst, to give mixture of the fumarate and maleate isomers (164) in the ratio 2 1. This mixture on heating undergoes a hetero-Cope rearrangement followed by cyclization and dehydration to give dimethyl 5-phenylpyrrole-2,3-dicarboxylate (168) (Scheme 25). Similarly, Heindel and Chun have reported that vinyl ether adducts (171), obtained by the condensation of arylamide oximes with DMAD, get thermally converted into oxa-diazolines (172) or imidazolinones (174), depending on the reaction conditions. A similar reaction occurs with aromatic amidoxime-methyl propiolate adducts to give imidazoles (170) (Scheme 26). 1,2,4-Dioxazoles have been reported to be formed in the reaction of hydrox-amic acids with DMAD. - ... 

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... 

The use of cycloaddition reactions for the synthesis of partially reduced heterocyclic systems was shown to be an attractive approach to dihydrobenzimidazoles, dihydroquinazolines, and dihydro-//n-benzopurines (Scheme 14) <86JOC6i6>. The dihydroxylation of the Diels-Alder adduct dimethyl 3,6-dihydrophthalate (128) with 0s04 and NMO followed by protection of the diol as the iso-propylidene derivative afforded compound (129). Saponification, dehydration with ethoxyethyne, and rearrangement with TMS—N3 effected conversion to the substituted tetrahydroisatoic anhydride (130), and subsequent treatment with formamidine acetate yielded compound (131). The substituents at the 6,7-positions of compound (131) were not amenable, however, for annelation of an imidazole. 

The reaction of 5,5-dimethyl-l-pyrroline 1-oxide with dimethylketene N-phenylimine leading to pyrrolo[l,2-a]imidazol-2(3H)-ones (190) proceeds via initial formation of zwitterion (188). Subsequent sigmatropic rearrangement of (188) gives zwitterion (189), capable of undergoing ring closure to (190) (79JOC4543). 

Like 2//-imidazoles, 4//-imidazoles also rearrange thermally to the more stable l//-compounds, but migration is to carbon in this instance thus 4,4-dimethyl-4//-imidazole 446 rearranges quantitatively to the 4,5-dimethyl-l//-isomer 447 by successive [l,5]-methyl and -hydrogen shifts. 

The scope of this methodology was established by forming imidazoles fused to five-, six- and seven-membered rings, 165, as outlined in Scheme 3856c,d. It was also found that while N-monosubstituted enaminonitriles such as 166 underwent photochemically mediated rearrangement to give imidazole 167, the reported conversion of 2-(dimethyl-amino)-1 -cyclohexene-1 -carbonitrile to 1,2-dimethyl-4,5,6,7-tetrahydrobenzimidazole could not be reproduced, i.e. no reaction was observed with A, 7V-disubstituted enaminonitriles5 6cd 58. 

Under conditions of thermolysis, photolysis and hydrogenation certain isoxazoles can be converted into imidazoles. For example, merely heating 5-amino-3,4-diaUcylisoxazoles at 180-190°C gives 40-65% yields of 4,5-dialkylimidazolln-2-ones in what initially appears to be a Dimroth-type rearrangement. Compounds such as 4-mcthyl-5-propyl-, 4-butyl-5-propyl, 5-benzyl-4-methyl-, 4,5-dimethyl- and 4-ethyl-5-methylimidazoles can be formed in the same way, but only if urea is present and if the reaction is carried out in the condensed phase. Without the added urea (or an arylamine) the yields are only 40-65% with urea they reach 70-90% [29-31]. 

Anthracene, 9,10-dihydro-9,9-dimethyl-as antidepressant, 1, 169 Anthracene, 1,4,5,8,9-pentamethyl-synthesis, 2, 537 Anthracyclinones synthesis, 1, 414, 4, 700 Anthramycin synthesis, 7, 614 Anthranil, 3-acyl-rearrangement, 5, 93 Anthranil, 3-aiyl-acridones from, 2, 93 thermolysis, 5, 91 Anthranil, 3-(imidazol-2-yl)-rearrangement, 5, 433 Anthranil, 6-nitro-reactions... 

A related synthesis leads to 4-trifluoromethylimidazoles. Trifluoracetylated aldehyde dimethyl-hydrazones thermally rearrange to give mixtures of oxadiazines and imidazoles. Higher temperatures and more polar solvents suppress formation of the six-membered rings, while solvent variation also alters the proportions of the imidazole regioisomers. In carbon tetrachloride the major product is... 

Diaryl-2,4-dithiohydantoins, when refluxed with BF3 dimethyl etherate or mixtures of the former reagent with BF3 in toluene or chlorobenzene, are selectively methylated at the S2 atom and/or undergo the above-mentioned rearrangement to yield imidazole derivatives (89).226... 

Intramolecular addition processes involving latent carbenes have been reported twice. On one hand, the thermolysis of 2,2-dialkoxy-5,5-dimethyl-A -l,3,4-oxadiazolines (38) as latent carbenes formed bicyclic compounds (39) via an efficient and highly stereoselective formal 4- -1-cycloaddition process, carbene (40) being postulated as the key intermediate. On the other hand, the deprotonated carbenic forms of alkyne-tethered imidazolium (41) and 1,2,4-triazolium salts (42) have been found to undergo 6-exo-dig intramolecular addition, leading to zwitterionic intermediates (43) and (44) that rearrange to give 2-substituted imidazole (45) and bicyclic 1,2,4-triazole (46), respectively. ... 

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