1,2,3,4-Tetrahydroquinoline dehydrogenation

Reactions of 3- and 4-piperidone-derived enamines with a dienester gave intermediates which could be dehydrogenated to tetrahydroquinolines and tetrahydroisoquinolines (678). The methyl vinyl ketone annelation of pyrrolines was extended to an erythrinan synthesis (679). Perhydrophenan-threnones were obtained from 1-acetylcyclohexene and pyrrolidinocyclo-hexene (680) or alternatively from Birch reduction and cyclization of a 2-pyridyl ethyl ketone intermediate, which was formed by alkylation of an enamine with a 2-vinylpyridine (681). 

A few pyrolytic methods of synthesis are known, leading directly to the formation of pyridine rings by formation of the /3, y-bond. Alkylpyridines are obtained when unsaturated imines (116) or (117) are passed over heated zeolites (80IZV655) or alumina (72IZV2263). More dehydrogenation is achieved by the use of nickel or alumina, as in the synthesis of tetrahydroquinolines (118) or octahydrophenanthridine (119) (78IZV1446). 

The elimination of hydrogen is very common in plasmas. Dehydrogenation of compounds like tetraline, acenaphthene, tetrahydroquinoline or in-dane has been carried out with excellent results. Elimination of hydrogen... 

Because of the conjugation of the free electron pair on the nitrogen atom with the double bond, enamines react very readily with double bonds activated by electronegative groups. Addition of acrolein to l-methyl-2-ethylidenepyrrolidine, followed by dehydrogenation, led to 1,7-dimethylindole.260 In a similar addition to l-methyl-2-alkyl-d2-piperideines, l-methyl-8-alkyl-l,2,3,4-tetrahydroquinolines (75) were obtained.38 In the reaction scheme, the starting bases are considered to react as the tautomeric l-methvl-2-alkvlidenepiperidines (74). 

Another method to prepare chloroquine (3) involves reaction of 83 with methyl acrylate to get via 98 and 99 the adduct 100, which is converted into 7-chloro-l,2,3,4-tetrahydroquinoline-4-one (103). Reaction of 103 with novaldiamine (92) under dehydrogenating conditions gives chloroquine in about 25% overall yield [133] (Scheme 3). 

The condensation of the sodio derivative of l,3-diformyl-4-keto-1,2,3,4-tetrahydroquinoline (172) with ethyl acetonedicarboxylate has been reported to give the 5-formyl-9-hydroxy-5,6-dihydrophen-anthridine-8,10-dicarboxylate (173). (However, the material obtained from 173 by hydrolysis, decarboxylation, and dehydrogenation ... 

The SnCl2-reduction system has also been apphed in the reduetion of S 2 nucleophilic substitution products 583, alfording more functional quinolines, 4-(substituted vinyl)-quinolines 584, in moderate yields, with several exclusions of the formation of dihydroquinoline derivative 585 (Scheme 4.174). However, using compounds 586 as substrates without a ketone moiety, the ester group can also participate in the intramolecular cychzation, but the subsequent dehydrogenation does not occur and, therefore, tetrahydroquinolin-2-ones 587 were obtained in 51-62% yields (frans form only). From this study, the preference of the activated carbonyl group COR for cychzation has the order R = Me > Ph > O-alkyl. 

Normally, the A-arylimine is obtained by reaction of aldehyde and aniline in acidic condition. Either tetrahydroquinoline or its corresponding substituted quinoline can be generated in the Povarov reaction, depending on the reaction conditions. For instance, DDQ-promoted dehydrogenation, vacuum distillation under acidic condition, oxidation by air or Mn(OAc)3, and Pd/C-catalyzed aromatization of tetrahydroquinoline, provides the corresponding substituted quinolines in good to excellent yield. Since some tetrahydroquinolines are unstable under the reaction conditions, the corresponding substituted quinolines could be isolated as the sole products. Electron-rich olefin, such as vinyl enol ethers, vinyl sulfides, and silyl enol ethers, are widely used as dienophiles in the cycloaddition of A-aryl aldimines to obtain substituted tetrahydroquinolines. To access natural... 

In their study of the dehydrogenation reaction Wiesner et al. isolated not only XX and XXI but also a new lactam, C13H13NO (XXII), which was derived from XXI by dehydrogenation over Pd-C at 270°. Compound XXII was identical with the product obtained by treatment of tetrahydroquinoline with ethylacetoacetate and is represented in structure XXII (Scheme 4). When S3uithetic XXII was reduced with sodium amalgam it yielded a racemate with an IR-spectrum identical with natural XXI. Examination of the UV-spectrum of XX showed that it was very similar to that of m-acetylaminobenzoic acid but distinctly diiferent from that of the para isomer. The structure of XX is therefore either XX-A or XX-B (Scheme 4). Synthesis of both isomers by unequivocal methods showed clearly that XX-A is the correct structure. The synthetic racemate had an IR- and a UV-spectrum identical with that of the naturally derived product. 

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