5.6- Disubstituted imidazo

Disubstituted imidazo[2,l-f)][l,3,4]thiadiazoles (56 R, R, R = H, alkyl, cycloalkyl, aryl) are liquid crystals, and various properties of these compounds have been investigated <88ZORl92, 88ZOR199, 88ZOR1306, 90LC475>. 

Diaminoquinoline also reacts with aldehydes in nitromethane. In a molar ratio of 1 1 it gave 2-substituted 106, and in a molar ratio of 1 2,1,2-disubstituted imidazo[4,5-/]quinolines 107 were formed (85IJC372, 82MI4). 

Bromine in acetic acid attacked 2,5-disubstituted imidazo[ 1,2-b]... 

Disubstituted imidazo[2,l-ft]thiazoles 41 have been prepared (55JCS1695 57JCS566) by eyelization of 1,5-disubstituted 2-mereaptoim-idazoles 40 in eonc. hydroehloric aeid. The latter eompounds were synthesized via eyelization of the thiourea derivatives 39. No aldehyde (42) was isolated from the reaetion obviously the thiourea eyelized more readily by reaetion with the aldehyde than with the keto group. 

Antiviral 2,5-disubstituted imidazo[4,5-f]pyridines have been reported for the treatment of hepatitis C <2007BML390, 2007BML5111>. A method for the preparation of substituted l//-imidazo[4,5-f]pyridines as immune response modifiers has been reported <2007W0092641>. 6-Phenyl-l//-imidazo[4,5-f]pyridine-4-carbo-nitrile derivatives have been reported to act as cathepsin K and S inhibitors <2007USP179138>. Imidazo[4,5-4pyridine derivatives have also been prepared as C3A receptor antagonists <2007W0034277>. 

Reports from Kuhn and co-workers identified the reaction of stable car-benes with 1,2-dichloroethane to yield 2-chloro-l,3-disubstituted imidazo-lium chloride salts.58 The versatility of these salts has been demonstrated by Ishikawa and co-workers.59 Due to its strong electrophilicity, 2-chloro-l, 3-dimethylimidazolium chloride can be used in chlorination, oxidation, reduction and rearrangement reactions, in addition to being used as a dehydrating agent. 

Copper(I) cyanide in dimethylformamide displaces bromine in positions 5 or 6 of disubstituted imidazo[2,l-i][l,3,4]thiadiazoles (56) forming the corresponding heteroaromatic nitriles (Table 18) <83JHC1003, 88ZOR199). 

In the imidazo[l,2-a]pyridine series, nucleophilic displacement of halides from C-5 or from C-2 when assisted by an adjacent EWG, was documented in the first edition. In similar fashion the nitro group of (68) has been shown to be displaced by RS <81JOC1026>. Pcn-disubstituted imidazo[l,2-... 

NHCs are most commonly derived from A,A -disubstituted imidazo-lium salts (4.16) by deprotonation at C2 to give the free NHC, 4.15. This acts as a very powerful 2e donor, binding to a variety of ML fragments to give NHC complexes (4.17). These are often seen represented in one of two ways depending on whether we want to emphasize the carbene character of the product (4.17a) or else the alternative picture of a metal substituted arenium ring (4.17b). 

Veerabhadraiah et al. (89SUL167) treated 4,5-disubstituted 2-mercapto-imidazoles with 3-(a>-bromoacetyl)coumarins and obtained ketones that on subsequent cyclization with PPA furnished 2,5,6-trisubstituted imidazo[2,l-h]thiazoles 38. 

Several other azolopyridazine ring systems have been prepared by similar approaches <2002FA89, 2002JHC329, 2001MOL203, 2000MOL1187>. For example, 6-substituted imidazo[4,5-tf pyridazin-7-ones are obtained from the reaction of 1,2-disubstituted 4-aroylimidazole-5-carboxylates and hydrazines <2002JHC329>. 

The photorearrangement of pyrazoles to imidazoles is probably analogous, proceeding via iminoylazirines (isomerization enthalpy =42 kJ mol ) (82AHC(30)239) indazoles similarly rearrange to benzimidazoles (67HCA2244). 3-Pyrazolin-5-ones (65) are photochemically converted into imidazo-lones (66) and open-chain products (67) (70AHC(ll)l). The 1,2- and 1,4-disubstituted imidazoles are interconverted photochemically. 

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