Quinoline derivatives, formation

Polycyclic aromatic hydrocarbons, indole and quinoline derivatives, naphthylamines, azulenes Silica gel G Formation of oxidation products via the initially formed iodine complexes [15]... 

Quinoline derivatives are of major interest as bioactive compounds. A new method for the synthesis of polycyclic fused quinolines 4-207 was developed by Rossi and coworkers [71], who used the [2+2] cycloaddition of an alkyne 4-204 with enamines 4-205 to give 4-206 (Scheme 4.45). Thereby follows an annulation, with the formation of 4-207a-c. 

Quinoid-type chromophoric structures, reactions of, 21 36-37 Quinoline (QI), 12 723, 725-726 soluble dyes, 7 373t Quinoline-4-carboxylic acids, 21 190 Quinoline derivatives, 21 196-214 Quinoline-derived drugs, 21 197-198t Quinoline dyes, 21 196 Quinoline, formation of, 21 109. See also Quinolines... 

Formate esters behave as typical carbonyl compounds in reactions with a number of ylides, eliminating phosphine oxide and forming vinyl ethers, e.g. (33).35 Stabilized phosphoranes are able to condense with the carbonyl group of cyclic thioanhydrides (34).38 Quinoline derivatives, e.g. (35), are obtained from the condensation of dicar-boalkoxy-ylides with isocyanates.37 Benzoyl isothiocyanates and keto-phosphoranes give quantitative yields of (36), which are unreactive in Wittig reactions but can be readily oxidized by selenous acid.38 The products obtained from reactions (Scheme 9) with the triazolinedione (37) depend upon the stability of the ylide used.39... 

In contrast with the azoles, diazoles and their benzo derivatives tend to react with dichlorocarbene to yield the tris(diazolyl)methanes, presumably via the initial formation of the N-dichloromethyl derivative [6, 13]. Only in more activated polymethyl derivatives does reaction occur at a ring carbon atom. In a similar manner (7.7.1.B), 2-chloropyridine and 2-chloroquinoline react with dichlorocarbene at the ring nitrogen atom to yield, after nucleophilic displacement of the chloro group, the 1 -dichloromethyl-2-oxo derivatives (13-25%) [14] (Scheme 7.38). 2-Chlorobenzothiazole reacts in an analogous manner, but other pyridine and quinoline derivatives fail to react. It is also noteworthy that the dichloromethyl group is unusually stable and is not converted into the formyl group. 

Furthermore, the N-alkylation of 2-aminobenzyl alcohol 114 with ketones 115 in the presence of [IrCl(cod)]2 and KOH gave quinoline derivatives 116 (Equation 10.28) [52]. The reaction may be initiated by the formation of ketimine from 114 and 115, and the ketimine thus formed is oxidized by Ir catalyst and the 114 which serves as a hydrogen acceptor giving the corresponding aldehyde, which is eventually converted into quinoline 116 through intramolecular aldol-type condensation. 

Reaction of 2-aminobenzophenone with acetyl acetone in the presence of Bi(OTf)3 (5 mol%) results in the formation of 3-acetyl-2-methyl-4-phenylquinoline [117]. Various 1,3-diketones, acyclic ketones and cyclic ketone undergo the condensation with 2-aminoaryl ketones. The scope and generality of this process is illustrated with respect to various 2-aminoaryl ketones and a wide array of a-methylene ketones, and the results are summarized in Table 6. This method is free from side reactions such as the self-condensation of ketones, which is normally observed under basic conditions. Unlike reported methods, the present protocol does not require high temperature or drastic conditions to produce quinoline derivatives. 

Winterfeldt and Nelke have observed the formation of the enamine derivative 35 in the reaction of methyl o-aminophenylacetate (34) with DMAD, which is subsequently cyclized to 3-hydroxy-2-carbomethoxy-methyl-4-carbomethoxyquino e (36), in the presence of sodium methoxide. Acylation of the quinoline derivative (36) leads to a furoquinoline (37) (Scheme 5)/ ... 

Koga et al. complexed oxo acids like methyl phenylphosphonate with bis(resorcinol) quinoline derivative 57 [83], Anslyn and coworkers presented a more rigid polyazacleft containing hydrogen bond acceptor and donor sites in form of pyridine rings and amino groups, respectively. The formation of the 3 1 complex 58 with dibenzyl phosphate is assumed, in which the four components are spatially fixed by a net of H-bonds [84]. 

Substituents in the pyranone ring are derived from the dicarbonyl component and hence variation in the nature of 3- and 4-substituents is relatively easy. Thus, ethyl benzoylacetate gives 4-phenylcoumarins as for instance in a synthesis of dalbergin (357) (76T2407, 8iiJC(B)9l8) and use of ethyl trifluoroacetoacetate leads to 4-trifluoromethylcoumarins. A study of the reaction of the latter with 3-aminophenol identified the optimum conditions for coumarin formation, but noted the simultaneous formation of the two quinoline derivatives (358) and (359) (80JOC2283). 

Reaction LIV. (c) Condensation of o-Aminobenzaldehydes with Aldehydes, Ketones, Ethyl acetoacetate, etc., under the influence of a trace of Sodium Hydroxide, to give Quinoline Derivatives (B., 16,1835 25,1752). —The first stage is the formation of an o-aminostyryl ketone. 

Eosine-sensitized photooxidations have been carried out on heterocyclic A/-arylena-mines, resulting in the formation of the corresponding carbonyl compounds11. With the analogous quinoline derivatives, oxidation at the -carbon atom was also observed (Scheme 11). 

Analogously, although the enhanced reactivity of quinoline derivatives (relative to pyridine counterparts) in nucleophilic additions such as the formation of pseudobases and Reissert compounds probably relates to the relatively lower energy of the LUMO in the quinoline derivatives, the radicals from these heterocycles, in which the corresponding orbitals are singly occupied, are anionic thus, reactivity toward nucleophiles is also unlikely to be important. 

R = CH3) was treated with acetic anhydride in the presence of sodium acetate. This reaction led to the formation of the quinoline derivative (204).218 With 203 (R = H) the rearrangement occurs to give 205 as... 

The formation of bonds c and b can take a couple of forms, either a Darzens-type approach (i.e., addition of a nucleophile bearing a leaving group) or addition of a carbene. Both of these routes have been used in the synthesis of fused-ring aziridines as well as monocyclic aziridines. The addition of a carbene or nucleophile such as an ylide to an imine can provide a nice route to fused-ring aziridines. The necessary cyclic imines are sometimes more readily obtained and used than the acyclic imines. These methods have largely been used on pyridine and quinoline derivatives. 

The remarks regarding the preparation of pyridine derivatives in the introduction to the preceding section apply also to the formation of quinoline derivatives. 

Niementowski quinoline synthesis. Formation of y-hydroxyquinoline derivatives from anthranilic acids and carbonyl compounds. 

Riehm quinoline synthesis. Formation of quinoline derivatives by prolonged heating of aryla-mine hydrochlorides with ketones with or without use of aluminum chloride or phosphorus pentachlo-ride. 

Fluoroalkylketenimines may be obtained from fluorinated alkenes and 60 undergoes a series of cycloaddition reactions, including formation of the quinoline derivative 61.149 Hexafluoroacetone azine (62) also reacts with acetylenes150 and the formation of pyrazoles (63) has been formulated as involving the quite novel migration of a trifluoromethyl group. 

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