Tetra hydroquinoline

Lithium aluminum hydride reduction of pyridinium salts is very similar to sodium horohydride reduction and gives similar products, but the ratio of 1,2- and 1,4-dihydro- or tetrahydropyridines differs considerably (5). Isoquinolinium salts are reduced hy sodium borohydride or lithium aluminum hydride in a manner identical to pyridinium salts (5). Quino-linium salts are reduced by sodium borohydride to give primarily tetra-hydroquinolines (72) as shown by the conversion of 33 to 34 and 35. When lithium aluminum hydride is used, the product is usually the dihydroquinoline (73) as shown in the conversion of 36 to 37 and 38. 

Pyrolytic ring closure of 3-o-aminophenyl-2,4-dioxo-l,2,3,4-tetra-hydroquinoline (172) gave a mixture of the a- and y-oxodihydro-carbolines 171 and 173. ... 

Researchers at Lilly have prepared a series of alkylamine H3 antagonists. Examples include the amide (57), which has a of 1.05 nM and the tetra-hydroisoquinoline (58), which has a A) of 0.37 nM [132]. Both compounds are inactive at the Hi, H2, and H4 receptors. This same group also disclosed a series of azepines, represented by (59) (H3 A j = 0.85 nM) and (60) [133]. Compound (60) is reported to have 100% bioavailability and a 12.4 h half-life in rat. Related dihydroindoles such as (61) (A j = 0.5nM) and tetra-hydroquinolines were also shown to be H3 antagonists [134]. 

These compounds usually show other reactions typical of their aliphatic analogues. 1,2,3,4-Tetra-hydroquinoline (532 Z = NH) is thus an /V-alkylaniline chroman (532, X = O) is an alkyl aryl ether. 

Vinylpyridines add to TV-alkyl- or phenyl-substituted maleimides to give unexpected 1 2 and 1 3 adducts. From the reaction of 2-vinylpyridine 99 with N-alkylmaleimides the 1 2 addition products 154, which are tetra-hydroquinoline derivatives, could be isolated in the presence of polymerization inhibitors. Furthermore, 1 3 adducts 155 are formed, representing an unusual type of cycloaddition involving the pyridine ring. On the other hand, 4-vinylpyridine 156 combines with 3 moles of dienophilic N-alkylmaleimides in the presence of polymerization inhibitors to afford the spiro compounds 157 (73HCA440). 

Examples of the versatility of photochemical hetero Diels-Alder photocycloadditions have also been reported. Thus, the 2,4,6-triphenylpyrylium terafluoroborate (TPT) photocatalyzed reaction of arylimines with N-vinyl-2-pyrrolidinone and N-vinylcarbazole represents a convenient approach for the preparation of tetra-hydroquinoline derivatives under mild conditions (Scheme 9.31) [52],... 

In a report describing new syntheses of substituted quinolines, furo[2,3-g]quinolines (34) and (35) were prepared in high yield from the same 7-allylquinolinol (Scheme 1) <83JOC774>. Reductive desulfonylation of these tricyclics with LAH gave 2-methylfuro[2,3-g]quinoline (36) and the unsubstituted parent heterocycle (37), respectively. The latter could also be prepared in good yield by a simultaneous desulfurization-aromatization route from 5-(phenylsulfonyl)-6-oxo-5,6,7,8-tetra-hydroquinoline. The versatility of this second route is demonstrated by the synthesis of the isomeric furo[3,2- ]quinoline (38) shown in Scheme 2. 

Aminocyclohex-2-en-l-one reacts with propiolaldehyde to yield 5-oxo-5,6,7,8-tetra-hydroquinoline (303) (equation 125)152. 

The results for tfiis reductive cyclization applied to several 2-(3-hy-droxyphenyl)ethyl ketone 0-2,4-dinitrophenyloxime derivatives 80 ate listed in Table 11. In all reactions, the corresponding 1,2,3,4-tetra-hydroquinolin-8-ol derivatives 83 were obtained regioselectively without any quinolines being formed. 

Cases in which decomposition of an azide results in the formation of a 6-membered ring are quite rare. In the thermolysis of (o-azido-phenyl)butane-n (289), 2-methyl-1,2,3,4-tetra-hydroquinoline (290) is only a minor product (10-20%)... 

Disubstituted pyridines.1 A typical reaction is the synthesis of 5,6,7,8-tetra-hydroquinoline (equation I). If the thermolysis is carried out in the absence of oxygen, the yield of the pyridine is 3%. 

EMD53986 [5-(l,2,3,4-tetra-hydroquinolin-6-yl)-6-methyl-3,6-dihydro-l,3,4-thiadiazin-2-one, Fig. B.l] is a chiral precursor for a pharmaceutical reagent. After chemical synthesis, it is present as a racemic mixture of the R- and S-enantiomers. The target component for the separation is the R-enantiomer. 

A mixture of 4-keto-6-chloro-l,2,3,4-letrahydroquinaldine, Pd-blaek, 30%-Pd-on-carbon, maleic acid as Ha-acceptor, K-carbonate. and water refluxed 24 hrs. — 4-hydroxy-6-chloroquin aldine. Crude Y 95%.— A pH of 9-10 is necessary, whereas the dehydrogenation of tetra-hydroquinolines proceeds smoothly at a pH of 7, without addition of K-carbonate. (F. e. s. E. C. Elderfield and A. Maggiolo, Am. Soc. 71, 1906 (1949).)... 

Partial C-debenzylation. An ethanolic soln. of 2,4-dioxo-3,3-dibenzyl-l,2,3,4-tetra-hydroquinoline hydrogenated with 5%-Pd-on-carbon until Hg-uptake ceases 4-hydroxy-3-benzylcarbostyril. Y ca. 100%. F.e. s.T.Kappe and E. Ziegler, Synthesis 1, 74 (1969). 

The [Ru(bpy)3] photocatalyst was also applied in the following novel visible-light driven processes (i) synthesis of indazolo[2,3-a]quinoline derivatives from 2-(2-nitrophenyl)-l,2,3,4-tetra-hydroquinolines (ii) azido- and amino-trifluoromethylation of alkenes (iii) reduction of nitro compounds to oximes (iv) generation of aryl radicals by visible-light photocatalytic reduction of sulfonium salts. ... 

In 2007, Crawford et al. observed a spontaneous enzymatically mediated DKR of 8-amino-5,6,7,8-tetrahydroquinoline in the presence of Candida antarctica lipase B, in which a >60% yield of the expected enantiopure (R)-acetamide was isolated from the racemic amine. " The spontaneous formation of 5,6,7,8-tetrahydroquinolin-8-one as a side product, followed by a con-densation/hydrolysis sequence with the remaining (5)-8-amino-5,6,7,8-tetra-hydroquinoline via the corresponding enamine, provided the necessary racemisation pathway (Scheme 3.52). 

A mixture of methyl 3-amino-6-chloro-4-hydroxy-l-methyl-4-phenyl-1,2,3,4-tetra-hydroquinolin-2-one-3-carboxylate, acetic acid, and benzene refluxed 3 hrs. -> methyl 7-chloro -1,3-dihydro -1- methy 1-5-phenyl - 2H-1,4 - benzodiazepin - 2 - one -3-carboxylate. Y 91%. F. e. s. A. Walser, A. Szente, and J. Hellerbadi, J. Org. Chem. 38, 449 (1973). 

In a same area, an efficient and simple method for the enantioselective synthesis of indolines, isoindolines, tetrahydroquinolines and tetraisoquino-lines was achieved by means of the organocatalytic intramolecular aza-Michael reaction of the corresponding aniline and benzylamine derivatives. " This process was catalysed by a diarylprolinol silyl ether used in the presence of benzoic acid as an additive, which provided the Michael adducts in good yields and excellent enantioselectivities of up to 99% ee (Scheme 1.85). This methodology was applied to the synthesis of the biologically active tetra-hydroquinoline alkaloid (-l-)-angustureine. 

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