Quinoline compounds reactions

PUtzing erReaction. Quinoline-4-carboxyhc acids are easily prepared by the condensation of isatin [91-56-5] (16) with carbonyl compounds (50). The products may be decarboxylated to the corresponding quinolines. The reaction of isatin with cycHc ketones has been reported, eg, the addition of cyclohexanone gives the tricycHc intermediate (17) [38186-54-8] which upon oxidation produces quinoline-2,3,4-tricarboxyhc acid [16880-83-4] (51). 

In summary, we may add that bacterial utilization of quinoline and its derivatives as a rule depends on the availability of traces of molybdate in the culture medium [363], In contrast, growth of the bacterial strains on the first intermediate of each catabolic pathway, namely, the lH-2-oxo or 1 II-4-oxo derivatives of the quinoline compound was not affected by the availability of molybdate. This observation indicated a possible role of the trace element molybdenum in the initial hydroxylation at C2. In enzymes, Mo occurs as part of the redox-active co-factor, and all the Mo-enzymes involved in N-heteroatomic compound metabolism, contain a pterin Mo co-factor. The catalyzed reaction involves the transfer of an oxygen atom to or from a substrate molecule in a two-electron redox reaction. The oxygen is supplied by the aqueous solvent. Certainly, the Mo-enzymes play an important role in the initial steps of N-containing heterocycles degradation. 

In other compounds, reaction can occur in both rings. Under such circumstances the orientation can depend on the conditions frequently reaction in the benzene ring involves the cationic species, whereas that in the pyridine ring involves the free base. Thus, the temperature dependent nitration of quinoline 1-oxide (578) reflects the decrease in intrinsic acidity as the temperature rises, which in turn increases the available amount of free base species. 

A similar electrophile, iodosyl triflate, CF3S020I0, was employed with arylsi-lanes [98]. The same reagent upon reaction with Me3SiCN formed (CN)2I+ TfO" which was coupled with tributyltin substituted arenes or heterocycles to afford bis(heteroaryl)iodonium triflates, e.g. dithienyl and difuryl derivatives [99]. However, this method gave poor results with nitrogen heterocycles. For them another approach was developed based on the reaction of the appropriate lithium compound with / -(dichloroiodo)chloroethylene (Scheme 33). Pyridine and quinoline compounds were formed in this way in moderate yield (23-71 %) [100]. 

The intramolecular cyclization of substituted 2-alkenylanilines (57) catalyzed by PdCl2 affords a novel route directly to 1,2,3-trialklylindoles (58), which can be further methylated to Fischer s base salts. The cyclization reaction is complex, and the reaction mixture contains much of the corresponding quinoline compound (59). The composition of the crude product and its yield depend strongly upon the nature of the substituents. The yields of pure indoles are moderate.63... 

A number of other miscellaneous systems that bear some relationship to Reissert compounds have also been reported but will not be covered in depth here. Thus, for example, the reaction of isoquinoline, potassium cyanide, and alkyl chloromethyl ethers give 116. A similar compound was also prepared from quinoline. Compounds of type 117 have been reported to undergo rearrangements similar to Reissert compounds. A... 

AllenylHthium compounds can function as nucleophiles for the synthesis of quinolines. The reaction of 3-methyl-1,2-butadienyllithium with phenyl isothiocyanate in THF at -70 C produces the allenyl thio-carboximidate, which can be thermally cyclized to 2-methylthioquinoline (Scheme 14). ... 

An interesting modification of Camps reaction was presented recently. It was based on the use of isatoic anhydride or benzoxazinones as active components for the in situ formation of intermediate amides, which were readily cyclized to the desired products. Thus, reaction of isatoic anhydride or benzoxazinones with malonates and/or ketoesters afforded libraries of quinoline compounds in high yields even at multikilogram scale. ... 

Hydroxy-quinoline carboxylates, prepared using the Could-Jacobs reaction, have also been frequently used as precursors for the synthesis of biologically interesting quinoline compounds. For example, the syndiesis of... 

The Doebner-von Miller reaction was used as a method of choice for the synthesis of several biological active quinoline compounds. The anti-malarial drug primaquine, which acts against the hepatic stage of plasmodia infection, was synthesized by a Skraup reaction fi om 4-methoxy-2-nitroaniline and glyceron in the presence of sulfiiric acid. The nitro group was then reduced and alkylated with 4-bromo-l-phthalimidopentane to provide the protected primaquine, which was deprotected by using hydrazine. ... 

Intramolecular or intermolecular Heck-type reactions were also used in the synthesis of poly-substituted quinoline compounds. Palladium-catalyzed reaction between vinyl or aryl halides and ortAo-allyl-substituted-A -tosyl-anilides produces dihydroquinolines in an intermolecular fashion, where reaction of acrylates intramolecularly affords 4-quinolones. ° ° ... 

Anhydrous tetrabutylammonium fluoride will replace the chlorine on a number of pyridine and quinoline compounds (Scheme 17). A number of 3- and 5-chloropyridines undergo fluorination in high yields. The reaction tolerates various functional groups including esters, cyano, and arenes. Moreover, chlorines on phenyl rings are left untouched. Difluorination of electron-deficient 4,5-dichloropyridines also proceeds in good yields (58— 85%). Finally, both quinoline and isoquinoline were fluorinated in almost quantitative yields (14JOC5827). 

X.-S. Wang, M.-M. Zhang, Z.-S. Zeng, D.-Q. Shi, S.-J. Tu, X.-Y. Wei, Z.-M. Zong, Tetrahedron Lett. 2005, 46, 7169-7173. A simple and clean procedure for the synthesis of polyhydroacridine and quinoline derivatives reaction of Schiff base with 1,3-dicarbonyl compounds in aqueous medium. 

The reaction between phthalonitrUe and copper also takes place readily in feoihng quinoline or a-methyhiaphthalene the pigment is precipitated as fast as it is formed as a crystalline product. It is separated from the excess of copper by shaking with alcohol, when the metal sinks and the pigment, which remains in suspension, can be poured off the process may be repeated to give the pure compound. 

Synthesis and Properties. Polyquinolines are formed by the step-growth polymerization of o-aminophenyl (aryl) ketone monomers and ketone monomers with alpha hydrogens (mosdy acetophenone derivatives). Both AA—BB and AB-type polyquinolines are known as well as a number of copolymers. Polyquinolines have often been prepared by the Friedlander reaction (88), which involves either an acid- or a base-catalyzed condensation of an (9-amino aromatic aldehyde or ketone with a ketomethylene compound, producing quinoline. Surveys of monomers and their syntheses and properties have beenpubhshed (89—91). 

Treatment of quinoline with cyanogen bromide, the von Braun reaction (17), in methanol with sodium bicarbonate produces a high yield of l-cyano-2-methoxy-l,2-dihydroquinoline [880-95-5] (5) (18). Compound (5) is quantitatively converted to 3-bromoquinoline [5332-24-1], through the intermediate (6) [66438-70-8]. These conversions are accompHshed by sequential treatment with bromine in methanol, sodium carbonate, or concentrated hydrochloric acid in methanol. Similar conditions provide high yields of 3-bromomethylquinoHnes. 

Reduction. Quinoline may be reduced rather selectively, depending on the reaction conditions. Raney nickel at 70—100°C and 6—7 MPa (60—70 atm) results in a 70% yield of 1,2,3,4-tetrahydroquinoline (32). Temperatures of 210—270°C produce only a slightly lower yield of decahydroquinoline [2051-28-7]. Catalytic reduction with platinum oxide in strongly acidic solution at ambient temperature and moderate pressure also gives a 70% yield of 5,6,7,8-tetrahydroquinoline [10500-57-9] (33). Further reduction of this material with sodium—ethanol produces 90% of /ra/ j -decahydroquinoline [767-92-0] (34). Reductions of the quinoline heterocycHc ring accompanied by alkylation have been reported (35). Yields vary widely sodium borohydride—acetic acid gives 17% of l,2,3,4-tetrahydro-l-(trifluoromethyl)quinoline [57928-03-7] and 79% of 1,2,3,4-tetrahydro-l-isopropylquinoline [21863-25-2]. This latter compound is obtained in the presence of acetone the use of cyanoborohydride reduces the pyridine ring without alkylation. 

Hydroxyquinolines (Quinolinols). A number of methods have been employed for their preparation. A modified Chichibabia reaction of quinoline ia fused KOH—NaOH at 240°C produces 70% of 2-hydroxyquiQoline [59-31-4] (121). Alternative names based on the facile keto—enol tautomerism of two of these compounds are 2(1H) and 4(lJd)-quiQolinone none of the other quinolinols show this property. The treatment of... 

The dimsyl ion also adds to carbon—carbon double bonds, and if the mixture is heated for several hours, methanesulfenate is eliminated. The overall result is methylation, and for compounds such as quinoline or isoquinoline (eq. 20), yields ate neady quantitative (50). The reaction sequence for isoquinoline to 1-methyhsoquinoline is as follows ... 

Phenols. Phenols are unreactive toward chloroformates at room temperature and at elevated temperatures the yields of carbonates are relatively poor (< 10%) in the absence of catalysis. Many catalysts have been claimed in the patent Hterature that lead to high yields of carbonates from phenol and chloroformates. The use of catalyst is even more essential in the reaction of phenols and aryl chloroformates. Among the catalysts claimed are amphoteric metals or thek haUdes (16), magnesium haUdes (17), magnesium or manganese (18), secondary or tertiary amines such as imidazole (19), pyridine, quinoline, picoline (20—22), heterocycHc basic compounds (23) and carbonamides, thiocarbonamides, phosphoroamides, and sulfonamides (24). 

---