Quinoline bromides

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. 

Additional pyrimido[4,5-f ]quinoline syntheses include one involving the action of cyanogen bromide on 2-chloro-3-cyanoquinoline similar to that described for pyridines (Section 2.15.5.5.1) (78JHC877), and a synthesis of pyrimido[4,5-fe]quinoline-2-carboxylic... 

Triphenylethylene has been prepared by the reaction of phenylmagnesium bromide with benzyl benzoate, with desoxy-benzoin, or with ethyl pheaniylacetate, and by the reaction of diphenylketene-quinoline with benzaldehyde. The above procedure is an adaptation of that described by Hell and Wiegandt. ... 

Primary halides are more reactive than secondary compounds quaternary salt formation does not occur with tertiary halides, elimination always occurring to give the hydriodide and an olefln, Also, the larger the alkyl group the slower is the reaction this is shown by the very slow reaction of dodecyl bromide with quinoline, and even butyl iodide is much slower to react than methyl iodide. The longer chain primary halides commonly undergo elimination rather than cause quaternization for example, n-octyl and cetyl iodides give only the hydriodides when heated with 9-aminoacridine. ... 

Alteration of the relative reactivity of the ring-positions of quinoline is expected and observed when cyclic transition states can intervene. Quinoline plus phenylmagnesium bromide (Et20,150°, 3 hr) produces the 2-phenyl derivative (66% yield) phenyllithium gives predominantly the same product along with a little of the 4-phenylation product. Reaction of butyllithium (Et 0, —35°, 15 min) forms 2-butylquinoline directly in 94% yield. 2-Aryl- or 6-methoxy-quinolines give addition at the 2-position with aryllithium re-agents, and reaction there is so favored that appreciable substitution (35%) takes place at the 2-position even in the 4-chloroquinoline 414. Hydride reduction at the 2-position of quinoline predominates. Reaction of amide ion at the 2-position via a cyclic... 

The nitration of l,2,5-selenadiazolo[3,4-/] quinoline 77 with benzoyl nitrate affords the 8-nitro derivative 78, whereas methylation with methyl iodide or methyl sulfate afforded the corresponding 6-pyridinium methiodide 79 or methosulfate 80, respectively (Scheme 29). The pyridinium salt 80 was submitted to oxidation with potassium hexacyanoferrate and provided 7-oxo-6,7-dihydro derivative 81 or, by reaction of pyridinium salt 79 with phenylmagnesium bromide, the 7-phenyl-6,7-dihydro derivative 82. Nucleophilic substitution of the methiodide 79 with potassium cyanide resulted in the formation of 9-cyano-6,9-dihydroderivative 83, which can be oxidized by iodine to 9-cyano-l,2,5-selenadiazolo [3,4-/]quinoline methiodide 84. All the reactions proceeded in moderate yields (81IJC648). 

The proposed structure of 97 isolated from broiled sardines was confirmed by straightforward synthesis starting from5,6-diaminoquinolines. After reaction with cyanogen bromide it afforded the 2-amino-imidazo[4,5-/]quinolines 99 (R = H, Me), which was then converted into its 3-A-methyl derivative 100 by... 

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). 

Quinoxalines undergo facile addition reactions with nucleophilic reagents. The reaction of quinoxaline with allylmagnesium bromide gives, after hydrolysis of the initial adduct, 86% of 2,3-diallyl-l,2,3,4-tetrahydroquinoxaline. Quinoxaline is more reactive to this nucleophile than related aza-heterocyclic compounds, and the observed order of reactivity is pyridine < quinoline isoquinoline < phenan-thridine acridine < quinoxaline. ... 

Bromoquinolines behave in the Suzuki reaction similarly to simple carbocyclic aryl bromides and the reaction is straightforward. Examples include 3-(3-pyridyl)quinoline (72) from 3-bromoquinoline (70) and 3-pyridylboronic acid (71) (91JOC6787) and 3-phenyl-quinoline 75 from substituted 3,7-dibromoquinoline 73 and (2-pivaloylaminophenyl)boronic acid 74 (95SC4011). Notice that the combination of potassium carbonate and ethanol resulted in debromination at the C(7) position (but the... 

Dialkylquinolinyl boranes 83 and 86 were prepared from halogen/metal exchange of 3-bromoquinoline (70) with n-BuLi followed by quenching with Et2BOMe and Br-9-BBN, respectively. They are then coupled with bromides 84 and 87 to give 3-substituted quinoline derivatives 85 and 88, respectively (85H2375). 

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). 

The procedure described above is essentially that of Thomas.2 Nor-bomylene has also been prepared by the additon of ethylene to monomeric cyclopentadiene 3 [Org. Syntheses, 32, 41 (1952)], by dehydration of j3-norbomeol with phosphorus pentoxide,4 and by dehydrohalogena-tion of norbornyl chloride or bromide using quinoline.4-6... 

Aniinophenyl)-a,(J>-ynones react with nitrile oxides by domino [3 + 2] cycloaddition/annulation reactions, giving rise to isoxazolo[4,5-c]quinolines in satisfactory yields (434). Nitrile oxides undergo addition to allylzinc bromide to generate 5-butenylisoxazolines in good yields. The domino reaction combines 1,3-cycloaddition with Wurtz coupling (435). 

McCort employed Stille technology to join a SEM-protected 4-bromopyrrolo[3,4-c]carbazole to the 3-tributylstannyl derivatives of pyridine and quinoline [143]. Mdrour effected coupling of tributylvinylstannane and tributylallylstannane with bromide 196 to afford the expected products 197 in excellent yield [146]. 

Synthesis of quinolines by nucleophilic substitution of nitrogen atom in oxime derivatives was described by Narasaka and coworkers. /3-Aryl ketone oximes 297 in the presence of trifluoroacetic anhydride and 4-chloranil afforded quinolines 298 in 72-82% yield (equation 128). However, interaction of oxime 299 with 48% HBr at 105 °C proceeded with elimination of hydroxyimino group and gave 2,3-dimethoxynaphtho[l,2-fc]quinolizinium bromide (300) in 45% yield (equation 129). ... 

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