Some Quinolines Patterned as “Open Models” of a Modified Atebrin

Gilman, Henry; Christian, Robert; Spatz, Sydney M.

doi:10.1021/ja01210a021

Cited by 7 publications

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“…In earlier investigations in this laboratory (8,9,14,15) For personal use only. ) showed slight activity.…”

Section: Introductionmentioning

confidence: 92%

“…2-Arylpyridincs and aryllithiums give low yields of 2,6-diarylpyridines. From three different 2-arylpyridines three antimalarials modelled after the p l a s n~o~l~i n type have been prepared.In earlier investigations in this laboratory (8,9,14,15) For personal use only. ) showed slight activity.…”

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confidence: 92%

“…In earlier investigations in this laboratory (8,9,14,15) The best J-ields were obtained by conducting the reaction above 100' and forcing the addition of the aryllithium to the sluggish 2-arylpyridine.…”

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confidence: 99%

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Studies in the Preparation of Antimalarials From Pyridine

Gilman¹,

Edward²

1953

Can. J. Chem.

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The addition of aryllithium compounds to pyridine followed by air oxidation gives satisfactory yields of several 2-arylpyridines. These are readily oxidized by pcrbenzoic acid to 2-arylpyridine-N-oxides, from which 2-aryl-4-and 6-chloropyridines may be obtained. 2-Arylpyridincs and aryllithiums give low yields of 2,6-diarylpyridines. From three different 2-arylpyridines three antimalarials modelled after the p l a s n~o~l~i n type have been prepared.In earlier investigations in this laboratory (8,9,14,15) For personal use only. ) showed slight activity. Somewhat surprisingly, 2-ptolylpyridine also gave indications of activity. I t inay be significant that the active compounds are vinylogues of a-picoline and a 2-aminop)~idine, in both of which there exists the possibility of a tautolileric shift of hydrogen to the hetero nitrogen atom (19, pp. 32, 91) ; such a possibility has been suggested in explaining the antimalarial activity of atebrin (23) and other compounds (4). The general method of synthesis of these plasmoquin models is illustrated by the example below. The aryllithium was prepared in all cases by direct interaction of the appropriate aryl bromide with lithium. I t has been observed that p-anisyllithium metalates p-bromoanisole so that the reaction of the latter with lithium ordinarily yields a mixture of p-anisyllithium and 2-rnethoxy-5-bromophenyllithium (10). However, if the p-anisyllithium is prepared very rapidly, the extent of metalation is slight and relatively pure p-anisyllithium is obtained. CANADIAA' JOURNAL 01; C H E M I S T R Y . I.OL. 31The addition of an aryllithium to pyridiilegives an N-lithiodihydropyridine (VI), which hitherto has been converted to the desired 2-arylpyridine (VII) by heating above 100" and splitting out lithium hydride (5,25,26,27). Oxidation of the N-lithiodihydro intermediate with dry air gives, particularly in the cases of 2-o-anisyl-and 2-p-anisylpyridine, sig;ificantly improved yields, though in the case of the o-anisyl compound the yield is still low.Since this work was completed, the preparation of 2-phenylpyridine in 60% yield by oxidation with nitrobenzene of 2-phenyl-l,2-dihydropyridine (produced from (VI; R = H) when the reaction mixture is poured into water) has been reported (7).The attempt to prepare 2-phenylpyridine by coupling 2-brornopyridine with phenyllithium gave only a low yield of the desired compound; the isolation of pyridine from the hydrolyzed reaction mixture indicates that a halogennletal interconversion reaction took place, giving bromobenzene and 2-pyridyllithium. A similar reaction with 3-bromopyridine, using n-butyllithium, has been described by Gilman and Spatz (12).The nitration of 2-phenyl-and 2-p-anisylpyridine gave nitro compounds of known orientation (6, 16); however, it was necessary to establish the position of nitration of 2-p-tolylpyridine (VII; R = CH3). This was done by an independent synthesis of the product, 2-(3'-nitro-4'-methylpheny1)-pyridine (VIII; R = CHJ, by the reaction of diazotized 2-nitro-4-aminotolu...

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“…In earlier investigations in this laboratory (8,9,14,15) For personal use only. ) showed slight activity.…”

Section: Introductionmentioning

confidence: 92%

mentioning

confidence: 92%

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Studies in the Preparation of Antimalarials From Pyridine

Gilman¹,

Edward²

1953

Can. J. Chem.

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“…by Gilman and coworkers (73,74,75). A methyl group also has been used to block the 2-position (47,81).…”

Section: From 4-chloroquinolinesmentioning

confidence: 99%

“…A methyl group also has been used to block the 2-position (47,81). The Meisenheimer reaction could not be used to prepare the 4-chloro derivatives, for example, from 7-chloroquinoline (159), 8nitroquinoline (77), 6-methoxy-8-nitroquinoline (77), 8-quinolinesulfonic acid (159), 8-methylquinoline (73), or 3-chloroquinoline (160). This lack of generality, the preparation of the oxides, and the separation of isomers decrease the usefulness of this reaction.…”

Section: From 4-chloroquinolinesmentioning

confidence: 99%

The Chemistry of 4-Hydroxyquinolines.

Reitsema¹

1948

Chem. Rev.

140

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The Halogen‐Metal Interconversion Reaction with Organolithium Compounds

Jones

Gilman

2011

Organic Reactions

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The reaction of an organic halide with an organometallic compound in which the metal and the halogen atoms exchange laces is known as the halogen‐metal interconversion reaction. Numerous studies have established the fact that the halogen‐lithium interconversion is a general and widely applicable reaction. Many organic halides do not react satisfactorily with metallic lithium to form RLi compounds or with metallic magnesium to form Grignard reagents. However, the desired organolithium compound often can be obtained by a halogen‐metal Interconversion reaction. The halogen‐metal interconversion greatly extends the utility of organolithium and Grignard‐type reactions.

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Some Quinolines Patterned as “Open Models” of a Modified Atebrin

Cited by 7 publications

References 0 publications

Studies in the Preparation of Antimalarials From Pyridine

Studies in the Preparation of Antimalarials From Pyridine

The Chemistry of 4-Hydroxyquinolines.

The Halogen‐Metal Interconversion Reaction with Organolithium Compounds

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