Quinoline to 1,2,3,4-tetrahydroquinoline

TABLE 12.5 Selective Hydrogenation of Methyl-Substituted Quinolines to 1,2,3,4-Tetrahydroquinolines in the Presence of Sulfur Compounds or Carbon Monoxide ... 

Recendy, we found that A -allyl-o-vii rlaniline 44 gave 1,2-dihydroquinoline 45 by normal RCM and developed silyl enol ether-ene metathesis for the novel synthesis of 4-siloxy-1,2-dihydroquinoline and demonstrated a convenient entry to quinolines and 1,2,3,4-tetrahydroquinoline [13], We also have found a novel selective isomerization of terminal olefin to give the corresponding enamide 46 using rathenium carbene catalyst [Ru] and silyl enol ether [14], which represented a new synthetic route to a series of substituted indoles 47 [12], We also succeeded an unambiguous characterization of mthenium hydride complex [RuH] with ACheterocyclic carbene... 

Reductions with noble metal catalysts proceed smoothly (at 20°C) when the bases are in the form of hydrochlorides the free bases tend to poison the catalyst. A pyridine ring is reduced more easily than a benzene ring thus, 2-phenylpyridine gives 2-phenylpiperidine (384), quinoline gives 1,2,3,4-tetrahydroquinoline (385) and acridine gives 9,10-dihydroacridine (386). 

Table I gives the results from the experiments with [M(PC)] supported on Si02 The conversion of quinoline is almost exclusively to 1,2,3,4-tetrahydroquinoline with only traces of other products (<1%). No propylaniline, propylbenzene, propyl-cyclohexane, 5,6,7,8-tetrahydroquinoline or decahydroquinoline were noted. No change is noted in the conversions when the SiC>2 is activated in vacuo at 400°C prior to supporting the complex. When the hydrogenations are run at 200°C only low conversions are...

Many synthetic methods have been developed for the preparation of quinolines and 1,2,3,4-tetrahydroquinolines due to the interesting biological properties of quinoline-type alkaloids. Most of the synthetic methods are based on the elaboration of aniline derivatives and, as for the synthesis of tetrahydroquinolines, reduction of the corresponding quinolines is the main approach. Only a few methods have been reported for the construction of the quinoline skeleton by N-C(8a) bond formation as the key step, such as oxidative cyclization of 2-(3-aminopropyl)benzene-1,4-diol 89 with K2[Fe(CN)e] (Scheme 42)... 

RuHCl(PPh3)3] and [RuH2(PPh3)2(PPh2C6H4)] can reduce polyaromatic compounds under hydrogen. Quinoline (67) and phenanthridine (69) are converted to 1,2,3,4-tetrahydroquinoline (68) and 9,10-dihy-drophenanthridine (70). ... 

Finally, formic acid may be mentioned, for it was used to convert cyclic imonium compounds into saturated tertiary amines125,126 and 1,2-dihydro-quinolines into 1,2,3,4-tetrahydroquinolines 127... 

In the quinoline ring system, the heterocyclic ring is more easily reduced than the benzene ring, forming tetrahydro-compounds or even decahydroquinoline derivatives under hydrogenation conditions. Quinolines have also been reduced to 1,2,3,4-tetrahydroquinolines by zinc borohydride and dimethylaniline under sonication conditions or with indium metal in... 

In efforts to develop industrial processes for the manufacture of nicotinic acid, Russian workers have studied the electrolytic oxidation of alkylpyridines and quinolines (X-74) using neutral or acidic media and platinum and lead anodes. Reactions occurred at 40 to 100° with high current efficiencies, but reported yields are low (Desired products appeared, of course, in the anolyte compartment. In the catholyte compartment, on the other hand, quinoline substrate was, inter alia, reduced to 1,2,3,4-tetrahydroquinoline (X-7S), isolated as the. /V-acetyl derivative. 

Hydrogenation of Quinolines Under Water Gas Shift Conditions and Oxidation of 1,2,3,4-Tetrahydro-quinolines to Hydroxamic Acids 6-Methoxy-1,2,3,4-tetrahydroquinoline and 1-Hydroxy-6-methoxy-3,4-dihydroquinolin-2(1 H)-one. 

The enantioselective hydrogenation of olefins, ketones and imines still represents an important topic and various highly enantioselective processes based on chiral Rh, Ru or Ir complexes have been reported. However, most of these catalysts failed to give satisfactory results in the asymmetric hydrogenation of aromatic and heteroaromatic compounds and examples of efficient catalysts are rare. This is especially the case for the partial reduction of quinoline derivatives which provide 1,2,3,4-tetrahydroquinolines, important synthetic intermediates in the preparation of pharmaceutical and agrochemical products. Additionally, many alkaloid natural products consist of this stmctural key element. 

In a typical experiment quinoline (20 mg), catalyst (1-2 mol %) and Hantzsch dihydropyridine (2.4 equiv) were suspended in benzene (2mL) in a screw-capped vial and flushed with argon. The resulting mixture was allowed to stir at 60 °C for 12 h. The solvent was removed under reduced pressure and purification of the crude product by column chromatography on silica gel afforded the pure 1,2,3,4-tetrahydroquinoline. 

Sodium cyanide in DMF at 120 °C has been used for the decarboxylation of 1-substituted-4-oxoquinoline-3-carboxylic acids <94TL(35)8303>. Quinoline Reissert adducts have been epoxidized at the 3,4-bond. Its reaction with amine nucleophiles gave regiospecifically substituted 1,2,3,4-tetrahydroquinolines <95H(41)897>. Successive Claissen rearrangements of 2-(8-quinolinoxymethyl)-3-(8-quinolinoxy)-l-propene gave a product which shows excellent ability to extract heavy metal ions <95TL(36)5567>. An Eschenmoser approach has been used in a facile synthesis of monofunctional and difunctional A -substituted-4-alkylidenequinolines (54) (Scheme 39) <95S(St)56>. 

Acidic media in the hydrogenation of quinolines may be avoided by the use of Rh/Al2C>3 as catalyst. Selective reduction may then be effected in hexafluoroisopropanol or methanol <2004SL2827>. Use of methanol leads to the isolation of the corresponding 1,2,3,4-tetrahydroquinoline while performing the hydrogenation in hexafluoroisopropanol results in total reduction to the decahydro product. 

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