2- 4-tetrahydroquinoline

Tetrahydroquinoline Tetrahydro-iso-quinoline Indole Carbazole Piperazine... 

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. 

Tests with laboratory-reared P. papatasi show that the duration of complete protection (no bites) provided by DEET, (9-ethoxy-W,A/-diethylbenzamide, (9-chloro-W,W-diethylbenzamide, or A/-butyryl-l,2,3,4-tetrahydroquinoline, averages at least 4 h, but perspiration contributes to a high rate of repellent loss... 

Oxamniquine. This tetrahydroquinoline (2), C24H2 N202, has been proven effective for the treatment of S. mansoni infections. It is clinically ineffective against S. haematobium and S.japonicum infections. 

Fig. 8. Thymidylate synthase inhibitors designed to fit into the A/, AJ -methylenetetrahydrofolate binding site. The best inhibitors from each class are the classical antifolate TS inhibitor (31), the naphthostyril-based lead compound (32), and the tetrahydroquinoline-based lead compound (33), iC values (in nAI)...

A mixture of 66.5 g. (0.5 mole) of tetrahydroquinoline and 400 g. of trimethylene chlorobromide (Note 1) is placed in a 1-1. round-bottomed flask attached to a reflux condenser, and heated in an oil bath held at 150-160° for 20 hours (Note 2). The reaction mixture is cooled, a solution of 50 ml. of concentrated hydrochloric acid in 500 ml. of water is added, and the excess trimethylene chlorobromide is removed by distillation with steam (Note 3). The acid residue from the steam distillation is made alkaline with a 40% solution of sodium hydroxide (about 75 ml.), and the julolidine is extracted with two 150-ml. portions of ether. The ethereal solution is washed with ISO ml. of water and dried over sodium hydroxide pellets. The ether is evaporated and the residue distilled under reduced pressure. The portion that boils at 105-110°/ mm. is collected (Notes 4 and 5). The yield is 67-70 g. (77-81%). 

The tetrahydroquinoline and trimethylene chlorobromide were Eastman grade materials of the Eastman Kodak Company. 

Julolidine has been prepared by the reaction of trimethylene chlorobromide with formanilide, aniline, methylaniline, and tetrahydroquinoline by the reduction of 8,10-diketojuloli-... 

Tetrahydroisoquinoline is a stronger base than tetrahydroquinoline. The unshared electron pair of tetrahydroquinoline is delocalized into the aromatic ring, and this substance resembles aniline in its basicity, whereas tetrahydroisoquinoline resembles an alkylamine. 

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). 

Sodium borohydride reduction of 4-substituted isoquinolinium salts led to vinylogous cyanamides, ureas, and urethanes, as well as the corresponding tetrahydroquinolines (640). Hydrogenation of /8-acylpyridinium salts (641) to vinylogous ureas was exploited in syntheses of alkaloids (642), leading, for instance, to lupinine, epilupinine, and corynantheidine (643, 644). Similarly, syntheses of dasycarpidone and epidasycarpidone were achieved (645) through isomerization of an a,/0-unsaturated 2-acylindole and cyclization of the resultant enamine. 

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). 

Nicolaou in his model system for an approach to the thiopeptide antibiotic thiostrepton, in particular, the elaboration of the quinaldic acid moiety. The tetrahydroquinoline 21 was converted to the A-oxide by /n-CPBA oxidation. Subsequent treatment with TFAA, to carry out the Boekelheide reaction, was followed by hydrolysis of the resultant ester to produce 22 as a mixture of alcohols. 

The mechanism of oxidation (16 —> 17) is not well understood. Both tetrahydroquinoline (19) and A-alkylaniline (20) have been isolated from reaction... 

The 6-methylacetylamino-l,2,3,4-tetrahydroquinoline, after nitration and separation of isomers, following reduction and deprotection, gave the 7-amino-6-methylamino derivative, which cyclized with cyanogen bromide. Alkylation of the cyclization products afforded inhibitors of thymidylate synthase, 5-substituted 2-amino-l//-l-methyl-5,6,7,8-tetrahydroimidazo[4,5-g]quinolines 136, designed for use in iterative protein crystal analysis (Scheme 42) (92JMC847). 

The relative ease of the reaction with the (l,l-dicyanopentynyl)pyrimi-dines induced studies of the reaction of 5-R-2-(l,l-dicyanohex-5-yn-1-yl)pyrimidine (R = H, NO2, Ar). They react with more difficulty, due to the longer tether between diene ad dienophile leading to a decreased entropic assistance. At a considerable higher temperature than observed for the (l,l-dicyanopentynyl)pyrimidines (210°C instead of 130°C and 8,8-dicyano-5,6,7,8-tetrahydroquinolines are formed (89T5151) (Scheme 33). 

Electron transfer initiated photocyclization of a methanolic solution of 90 followed by catalytic hydrogenation gave a mixture of benzoindolizines 91 and tetrahydroquinoline. Hydrogenation is necessary to stabilize one of the proposed products (82TL919, 83JA1204) (Scheme 17). 

Reaction of tetrahydroquinoline 257 with ethyl bromopyruvate afforded pyrroloquinoline 260 which upon transesterification by treatment with tropine in presence of sodium methoxide in toluene gave 261 which was found to be useful as 5-HT receptor antagonist (89EP322016). 

A synthesis for the enantiomerically pure 535 was developed starting with D-phenylalanine which upon reaction with methyl chloroformate gave 528 whose reaction with methoxylamine afforded 529. Cyclization with bis(trifluoroacetoxy)iodobenzene in presence of trifluoroacetic acid gave the tetrahydroquinoline derivative 530 which was demethoxylated to give 531. Treatment of 531 with either benzyl chloroformate or... 

Phenyl-5,6-dihydro-l//,7//-pyrido[3,2,l-//]quinazoline-7-one and 1,7-dione 179 (X = H2 and O) were prepared from tetrahydroquinolines 206 and 207 with A-(ethoxycarbonyl)thiobenzamide and PhCOCl, respectively (98EJM763). 

R = Ar) and cyclized tricyclic compound 240 (R = Ar) was obtained when 2-bromoacetophenones were reacted with 8-hydroxyquinolin-2(l//)-one under the above conditions. Presence of a 4-methoxy substituent shifted the equilibrium to the ring-opened product 241 (R = 4-MeOPh), while that of 4-nitro group gave only cyclized product 240 (R = N02). Similarly, mixtures of ring-opened and 2,3,6,7-tetrahydro-5//-pyrido[l,2,3- /e]-l,4-benzoxazin-5-one derivatives were formed in the reaction of 8-hydroxy-l,2,3,4-tetrahydroquinolin-2-one and halomethyl ketones (00HCA349). 

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