Quinoline substitution

The reaction of /V-henzylideneaniline (19) with alkynes leads to quinolines substituted in the heterocychc ting (56). Except for benzyhdenes bearing nitro substituents, the reaction occurs in good yield and under mild conditions. The method appears capable of elaboration. 

The first reaction series to be considered are the basicities of the various quinolines. Baciocchi and Illuminati have demonstrated that the pK values of quinolines substituted in the B-ring follow the Hammett equation well if ApK, i.e., the difference between the pK values of substituted and unsubstituted compounds, is plotted against a, the quinoline points fall on the same line as the pyridine points, as shown in Fig. 5, so that the p-values for the two series are identical. 

Quinolines substituted at the pyridine ring may be obtained by using a substituted a ,/3-unsaturated aldehyde or ketone instead of the glycerol as starting material. However often a large amount of the carbonyl component polymerizes under the reaction conditions. 

Synthesis of Quinolines Substituted in the Carbocyclic Ring via Directed Mktalation... 

Reaction UV. (b) Condensation of Primary Aromatic Amines, other than Ortho Substituted, with two Molecules of certain Aldehydes (containing the group—CELjCHO) under the influence of Sulphuric or Hydrochloric Acid. (B., 16,2415 A., 249,110.)—Quinolines substituted in the benzene or in both nuclei may be formed, anils being formed intermediately. 

R. Ring opening reactions of quinoline-substituted epoxides. Tetrahedron Lett. 2003, 44, 9299-9302. 

Dihydroquinoline-5-ones are obtained by cyclocondensation of 3-aminoacroleins with cyclohexan-l,3-diones or 3-ethoxyacrylaldehydes and aminocyclohexenone. The corresponding ketone (R1 = Me) behaves analogously235 (equation 169). The unexpected pattern of the quinoline substitution therefore can be reasonably ascribed to intermediate transamination between the 1,3-dicarbonyl components. 

Figure 30. The DSC traces of mononuclear Cu(II) (a-e, solid trace) and Zn(ll) (a-b, dotted) metaUenediynes along with their dinuclear Zn(II) counterparts (c-e, dotted). The code in each spectrum denotes the number of additional carbons in the arms at the aUcyne termini on each side of the molecule and s or a represents symmetric or asymmetric R group (a) 3-hydroxypyridine di-methylamine b) 3-hydroxypyridine (c) 3-hydroxypyridine quinoline (d) quinoline (e) 3-pyridine quinoline) substitution.

Pumiliotoxin C alkaloids. Alkaloids of this general type are c/s-decahydro-quinolines substituted at C2 and C5. Overman and Jessup have devised a general synthesis for these alkaloids, shown in equation (1) for synthetic equivalent of trans- -amino-1,3-butadiene, with a j3-alkyl-substituted rrans-a, -unsaturated aldehyde. Thus the dienecarbamate 1 reacts with /ra s-crotonaldehyde at 100° (2.5 hours) to form a single adduct (2) in 617o yield (10-15% of 1 is recovered). Wittig-... 

Similar excitation distributions and CT diagrams are obtained for nn excitations in heteroaromatic systems. Some interesting systems are treated in [70] by using the ESSA/TDDFT analysis for proton phototransfer processes. In particular, for the first excited nn state in the quinoline-substituted 3-hydroxychromone one observes the pronounced localization picture which can be revealed in the corresponding CT diagrams (see Table 2 in [69]). 

In order to further develop the SAR of this series, it was necessary to determine the effect that quinoline substitution had on fun cidd activity. To answer this question, a number of mono-,di-,and trisubsdtuted quinolines were synthesized, holding constant the phenylethylamino group in the 4-posidon of the quinoline. 

It would appear that, for the most part, substitution on the quinoline does not improve the activity of the corresponding phenylethylquinoline. The activity of the quinoline substitute analogs is more negatively effected by substitution in Ae pyrido portion than the benzo-portion. However, some substitutions in the 8-position, especially the fluorine, 13, either have at least comparable activity or are more active than the unsubstituted quinoline analog. 

Primary candidates for the mutagens (and carcinogens ) responsible for activity in the basic fractions include quinoline, substituted quinolines, alkyl pyridines, acridines, aza-arenes, naphthylamines, and aromatic amines in the neutral fractions, potential hazards may be benzanthracenes, dibenzanthracenes, substituted anthracenes, benzopyrenes, benzofluorenes, pyrene, substituted pyrenes, and chrysenes. 

A microwave-assisted, diversity-oriented, inverse electron-demand [4+2] cycloaddition of functionalized 1,2,4-triazines with alkyne dienophiles was carried out (Hajbi et al., 2008). 2,3-Dihydrofuro[2,3-b]pyridines and 3,4-dihydro-2H-pyrano-[2,3-b]pyridines on functionalization at the 3 and 4 positions have close structural similarity with well-known potent serotonineigic ligands like quinolines, substituted pyridines, and chromanes. 

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