Brominations quinoline

Simple quinolines and quinolin-4-ones often occur outside of the Rutacae plant family, thus the brominated quinoline (1) is metabolised by the marine bryozoan Flustra foliacea (P. Wulff, J.S. Carle and C. Christophersen, Comp.Biochem.Physiol.B, 1982, 71, 525) and an unusual... 

The blank determination must be made since even the number of drops, of methyl orange used in the titration will aflFect the results considerably —presumably the ethanol of the reagent being oxidised by the bromine. Quinoline yellow (4 drops of a 0-5 per cent aqueous solution) has been found satisfactory by Belcher as a reversible indicator in bromometric titrations. 

This coupling works best when the halogen at the 7-position is bromine rather than chlorine or fluorine. This represents the first appUcation of this coupling reaction to the intact quinoline nucleus and thus represents an important advance in quinolone chemistry. 

Treatment of quinoline with cyanogen bromide, the von Braun reaction (17), in methanol with sodium bicarbonate produces a high yield of l-cyano-2-methoxy-l,2-dihydroquinoline [880-95-5] (5) (18). Compound (5) is quantitatively converted to 3-bromoquinoline [5332-24-1], through the intermediate (6) [66438-70-8]. These conversions are accompHshed by sequential treatment with bromine in methanol, sodium carbonate, or concentrated hydrochloric acid in methanol. Similar conditions provide high yields of 3-bromomethylquinoHnes. 

A quinoline—bromine adduct in hot carbon tetrachloride containing pyridine gives a 90% yield of 3-bromoquinoline (21) 3-chloroquinoline [612-59-9] is prepared by an analogous route, but in poorer yield. A quinoline—aluminum chloride complex heated with bromine gives a 78% yield of 5-bromoquinoline [165-18-3] (22). Equal quantities of 5- and 8-bromoquinoline [16567-18-3] are formed when quinoline is treated with one equivalent of bromine in concentrated sulfuric acid containing silver sulfate (23). 

Quinoline, 2,4-bis(dimethylamino)-synthesis, 2, 419, 469 Quinoline, 3-bromo-bromination, 2, 319 oxidation, 2, 325 Skraup synthesis, 2, 467 Quinoline, 5-bromo-bromination, 2, 319 nucleophilic substitution, 2, 324 Quinoline, 6-bromo-nucleophilic substitution, 2, 324 Quinoline, 8-bromo-bromination, 2, 319 N-oxide... 

Hydroxyquinoline forms the complex with Cu(II) in ratio 1 1 at pH 5-7. The composition of the complex is changed on 1 2 at pH>7. 8-Hydroxy-quinoline accepts bromine therefore its excess has been removed with NaOH solution. The complex was extracted with chloroform. It was shown that double extraction was enough to extract the complex. The detection limit is 5x10 M during 10c and at current generation IxlO A. 

Deca/octahydro 6-alkyloxazolo /-fused quinolines 17 were prepared and evaluated as dopaminergics (87EUP1). A series of linearly annelated 8-alkyl-deca/ octahydrooxazoloquinolines 18 and their salts were prepared for use as dopamine D2-agonists and hypertensive agents. The rran.s-( )-l-propyl-6-oxodecahydro-quinoline was brominated, then treated with urea in methanol to give the 2-amino... 

It is difficult to treat the effect of a heteroatom on the localization energies of aromatic systems, but Brown has derived molecular orbital parameters from which he has shown that the rates of attack of the phenyl radical at the three positions of pyridine relatively to benzene agree within 10% with the experimental results. He and his co-workers have shown that the formation of 1-bromoisoquinoline on free-radical bromination of isoquinoline is in agreement with predictions from localization energies for physically reasonable values of the Coulomb parameters, but the observed orientation of the phcnylation of quinoline cannot be correlated with localization ener-... 

Bromination of the diphenyl indole derivative 316 with bromine in DMF or trimethylammonium bromide afforded the 7-bromo derivative 317. Reaction with allyl bromide or its derivatives gave A-allyl derivatives 318 that upon cyclization with palladium acetate gave 7,9-dimethoxy-l,2-diphenylpyrrolo[3,2,l-// ]quinoline derivatives 319 (92T7601) (Scheme 57). 

Bromination. Neutral bromination of quinoline (66) using bromine in hot carbon tetrachloride and pyridine gave the 3-bromo derivative (68) (90%) and 3,6-dibromoquinoline (69) (2%), along with traces of 3,8-di-and 3,6,8-tri-bromo products [59CI(L) 1449 66AHC(7)1]. There is some... 

With acetic acid as solvent 68 is still the major product (Scheme 32). The minor product (69) probably forms in preference to the 3,5-isomer because the quinoline free base is reacting the high yield of 68 can be rationalized in terms of a 1,4- or 1,2-addition product that is rapidly bromi-nated at C-3. The 6- and 8-positions substitute more slowly [62JCS283, 62JCS291 77HC(32-1)319]. Both the 6- and the 8-bromoquinolines were 3-brominated under neutral conditions (62JOC1318). 

Reactions in acetic anhydride with metal acetates present probably occur by 1,4-addition of bromonium acetate (85CHE458). When NBS in sulfuric acid at 20°C was used, the product ratio resembled that observed with bromine-sulfuric acid-silver sulfate. At 60°C the ratio changed to 2 1.2 1 as a consequence of more extensive dibromination (88CHE892) (Scheme 33). As might have been deduced, 2-(2 -thienyl)quinoline was brominated only in the thiophene ring (82CHE28). 

Bromine in acetic acid readily converted the activated 3-hydroxy-quinoline into its 4-bromo derivative (76%) under similar conditions 8-hydroxyquinoline gave a mixture of the 5-bromo and 5,7-dibromo compounds [71BAU400 72JOC4078]. All of the possible monobromo derivatives of the latter substrate have been made (91M935). 4-Hydroxy-... 

Vapor phase brominations have given rise to varying products dependent on the reaction temperature. At 300°C bromine converted quinoline in the presence of pumice into 68 (25%) at 450°C 2-bromoquinoline (25%) became the major product at 500°C the yield of the 2-bromo isomer increased to 53%, but there was some dibrominated material [77HC(32-1)319]. The absence of 3-bromoquinoline at the higher temperatures could be accounted for in terms of radical attack, or it could be due to thermal instability of that isomer [59CI(L)1449]. 

Among the nucleophilic processes available for introduction of bromine to quinolines are reactions of the diazonium salts (87JHC181) and syntheses based on hydroxyquinolines or quinolones (91M935) (Scheme 36). The former processes are especially useful for making 5-, 6-, 7-, and 8-bromo derivatives. Halogen-halogen exchange reactions have also been reported, but they are not common. When perfluoroquinoline was heated... 

Lateral bromination was observed in the reaction of NBS with 5-chloro-8-methyl- and some related methyl- and alkylthio-quinolines [83KFZ1055 86S835]. 

Variable results have been reported for the halogenation of thieno[2,3-6]quinoline (123). Initial attack was mainly at the 3-position, but it was difficult to avoid the formation of 2,3-dihalogenated products, even when only 1 mol of halogen was used (predictions are for 2- and 3-substitution [77ZN(B)1331]). Bromine buffered in chloroform gave the 3-monobromo derivative, but analogous chlorination gave a mixture that included some... 

Thieno[4,5-c]isoquinoline formed the 2,3-dibromo product in 60% yield, whereas the [3,4-c] isomer decomposed under the same conditions (89CS309). Thieno[3,2-/]quinoline was brominated in 57% yield at C-2 [70JCS(C)2334]. 

When position 6 on the 2-quinolone is blocked, bromination takes place selectively at the 3-position. Thus, microwave irradiation of 45 in acetonitrile at 150 °C for 50 min afforded the 3-bromo-quinolin-2(lff)-one 46 in 87% yield (Scheme 12). 

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