1,2,3,4-Tetrahydroquinolines

earlier etal, US Patent 6,472,408 (October 29, 2002) Assignee The Hong Kong University of Science and Technology Utility Treatment of Alzheimer s Disease 

8-Tetrahydro-5-oxo-2(lH)-quinolinone (4.0mmol), 1,7-diaminoheptane (2.0 mmol) and 5 drops of HO Ac dissolved in 50 ml benzene were refluxed with azeotropic removal of water for 24 hours. The solution was cooled, concentrated, and the Schiff base used directly in Step 2. 

The product from Step 1 was ground to a fine powder, suspended in 50 ml methyl alcohol, NaBH4 (7.6 mmol) in methyl alcohol added drop wise, and the mixture stirred at ambient temperature 12 hours. The precipitate that formed was filtered and washed with methyl alcohol and water. The filtrate was concentrated, purified by passing through a silica plug using methyl alcohol/NH40H, 50 1, from which additional material was obtained, and the product isolated in 50% yield, mp = 218-219°C. H- and C-NMR and MS data supplied. 

rac-/meso-N, N -Di-5 -(5, 6, 7, 8 -Tetrahydroquinolin-2-onyl)-l,7-diaminoheptane hydrogen chloride 

The product from Step 2 (200 mg) was dissolved in 10 ml methanolic HCl containing EtOAc and remained undisturbed for several days at ambient temperature. It was filtered, concentrated, and the product isolated in 67% yield, mp = 189-191 °C (dec.). H-NMR, HPLC, elemental analysis data supplied. 

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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. 

In a similar addition to l-methyl-2-alkyl-J -piperideines, l-methyl-8-alkyl-1,2,3,4-tetrahydroquinolines (134) were obtained (Scheme 10) (163). 

Substituted 1,2,3,4-tetrahydroquinolines (e.g., 61) are formed with high regio- and stereoselectivity in high yield by intermolecular [A+2] cycloadditions of cationic 2-aza-butadienes and various dienophiles <95CC2137,96SL34>. 

Scheme 10.13. Polyethylene glycol)-supported domino synthesis of 1,2,3,4-tetrahydroquinolines.

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 use of water-soluble metal catalysts for the hydrogenation of thiophenes in aqueous biphasic systems has been primarily introduced by Sanchez-Delgado and coworkers at INTEVEP S.A. [61]. The precursors RuHC1(TPPTS)2(L2) (TPPTS=triphenylphosphine trisulfonate L=aniline, 1,2,3,4-tetrahydroquinoline) and RuHC1(TPPMS)2(L2) (TPPMS=triphenylphosphine monosulfonate) were... 

The ring closure of N-(2-oxo-1,2,3,4-tetrahydroquinolin-5-yl)amino-methylenemalonate (705) by heating in polyphosphoric acid at 140°C for 30 min gave 1,7-phenanthrolinecarboxylate (706) in good yield [80JAP(K)69582],... 

Diethyl (5-acetamido-6-fluor-2-methyl-1,2,3,4-tetrahydroquinolin-l-yl)-methylenemalonate (130, R = F, R1 = NHAc) was cyclized by heating... 

Flumequine was prepared in 84% yield by the cyclization of isopropylidene (6-fluoro-2-methyl-1,2,3,4-tetrahydroquinolin-1 -yl)methylenemalo-nate in polyphosphoric acid at 120-130°C for 30 min [82JAP(K)2285],... 

The ring closure of (1,2,3,4-tetrahydroquinolin-l-yl)methylenemalonate was achieved by heating in polyphosphoric acid (89EUP323189). 

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... 

As shown in Scheme 5.23, 1,2,3,4-tetrahydroquinoline derivatives were synthesized using 3-(2-aminophenyl)propanols as starhng materials and catalyzed by the I/K2CO3 system. This catalytic system was also applicable to the synthesis of 2,3,4,5-tetrahydro-l-benzazepine from 4-(2-aminophenyl)butanol. 

The reaction between 1,1-diphenylethene and l-imino-l,2,3,4-tetrahy-droquinolinium ion, obtained by electrochemical oxidation of 1-amino-1,2,3,4-tetrahydroquinoline, furnished 3,3-diphenyl-l,2,3,7,8,9-hexahydro-pyrido[3,2,l-y]cinnoIine (66TL2583). 

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