1//-Imidazo quinoline

Figure 1. Suggested route for the formation of the imidazo-quinoline compounds.

FIGURE 7.3 Suggested pathway for the formation of imidazo-quinolines and hnidazo-quinoxalines. (Adapted from Jagerstad, M. et al. 1998. Z. Lebensm. Unters. Forsch. A 207 419-427. With permission.)... 

Ab initio calculations (STO-3G) on imidazo[4,5-/]quinolines have shown that in all cases (neutral, anionic, mono-, and dicationic) the 3H form 44a is favored over the IH form 44b [93THE(279)167]. 

FtG. 1. Energy values for the neutral and two alternative protonated forms of imidazo[4,5-/]-quinoline. 

The proposed structure of 97 isolated from broiled sardines was confirmed by straightforward synthesis starting from5,6-diaminoquinolines. After reaction with cyanogen bromide it afforded the 2-amino-imidazo[4,5-/]quinolines 99 (R = H, Me), which was then converted into its 3-A-methyl derivative 100 by... 

Calculated Proton Affinities and pK Values for Imidazo [4,5-/ Quinolines... 

Diamines formed upon photolysis of 6-quinolyl azide in isopropyl-, n-butyl-, and n-hexylamines are very unstable, so they were cyclized to the corresponding 1-substituted imidazo[4,5-/]quinolines by heating the residue obtained after evaporation of the photolysis solvent with formic acid at reflux (82JCS(P 1)421). Instead... 

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). 

Using different mono- and diketones in acetic acid (at room temperature) afforded the following products from benzophenone, 2,2-diphenyl-2//-imid-azo[4,5-/]quinoline from dibenzylketone, the 2-benzyl-imidazo[4,5-/]quino-line and from 2,4-pentanedione, 2-methyl-imidazo[4,5-/]quinoline. Cyclohexanone under reflux gave 2-n-pentyl-, whereas at room temperature it afforded the. s pira[cyclohexane-l,2 ]-(2//)-imidazo[4,5-/]quinoline 108 (R R =(CFl2)5) (86UC527). 

Trialkyl-2,3-dihydro-l//[l,4]diazepino[2,3-/]quinolines 109, obtained from the reaction of 5,6-diaminoquinoline with ketones, on treatment with acid or under thermal conditions afforded solely the 2-methyl-3//-imidazo[4,5-/]quino-line 110. However, no change was observed when diazepinoquinolines were treated... 

The same diamine, when treated with carbon disulfide in alkaline medium, yielded 2-mercapto- l//-imidazo[4,5-/]quinoline (88PS267,88SC973,86IJC264), which, on treatment with alkyl, aralkyl, and acid halides, gave the corresponding thioethers and thioesters 111, respectively (88PS267, 86IJC264). 

Angularly annelated 2-trifluoromethylimidazo[4,5-/] and [4,5-/i]quinoline have been prepared from 5(6)-acetamido-2-trifluromethylbenzimidazole and 7,8-di-aminoquinoline, respectively. They undergo hydrolysis in dilute sodium hydroxide to give parent skeletons imidazo[4,5-/] and [4,5-/i]quinoline 113,114 (Scheme 35) (81JFC573). 

The hydrolysis proceeds via a diazafulvene intermediate, which in these systems can be formed without a total loss of aromatic character of the tricycle. It is tempting to suggest that, using this reasoning, linearly annelated 2-trifluoromethyl-imidazo[4,5-g]quinoline should be inert toward alkaline hydrolysis, as formation of the diazafulvene intermediate will again involve total dearomatization of the heterocyclic system (Scheme 36). 

Absorption and emission spectra of six 2-substituted imidazo[4,5-/]quinolines (R = H, Me, CH2Ph, Ph, 2-Py, R = H CH2Ph, R = Ph) were studied in various solvents. These studies revealed a solvent-independent, substituent-dependent character of the title compounds. They also exhibited bathochromic shifts in acidic and basic solutions. The phenyl group in the 2-position is in complete conjugation with the imidazoquinoline moiety. The fluorescence spectra of the compounds exhibited a solvent dependency, and, on changing to polar solvents, bathochromic shifts occur. Anomalous bathochromic shifts in water, acidic solution, and a new emission band in methanol are attributed to the protonated imidazoquinoline in the excited state. Basic solutions quench fluorescence (87IJC187). 

The association of the excited state derived from four 2-substituted imidazo [4,5-/]quinolines with 2-propanol in cyclohexane has been studied. The unusual bathochromic shift and the bandwidth of the fluorescence spectra of these heterocyclic compounds in 2-propanol-cyclohexane solutions, compared with those... 

In the search for new fluorometric reagents for trace metal determinations, ferroin-type compounds, namely 2-(2-pyridyl)-2//- and 2-(3-isoquinolyl)-3//-imidazo[4,5-/i]quinolines, and their silver, lead, and zinc chelates were tested for luminiscence in aqueous ethanol solutions at various pH values (80TAL1021). 

In cyclization of 6-aminoethylene substituted 1-methylbenzimidazole, an angularly annelated l//-l-methyl-8-ethoxycarbonyl-9-oxo-6,9-dihydroimidazo[5,4-/] quinolone 122 prevails over the sterically less hindered (9-oxo group vs 1-methyl group) linearly annelated imidazo[4,5-g]quinoline 123. Hydrolysis of the cyclization product produced the corresponding acid 124 (Scheme 39) (94CCC1145). 

Derivatives of 1 -ethy l-7-alkylamino-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 137 have been reduced to corresponding diamines 138 and afterwards converted exclusively to linearly annelated imidazo[4,5-g]quinoline-7-carboxylic acid derivatives 139 (Scheme 43) (88KFZ33). 

Polysubstituted imidazo[4,5-/]quinolines were prepared and evaluated by Spencer and Alaimo, but also by other authors for possible antihelmintic activity... 

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