An efficient method for the N-debenzylation of aromatic heterocycles

Haddach, Aubrey A.; Kelleman, Audrey; Deaton-Rewolinski, Melissa V.

doi:10.1016/s0040-4039(01)02192-x

Cited by 104 publications

(69 citation statements)

References 7 publications

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“…Apart from the mentioned hydrogenation and acid hydrolysis used by us the final stage where necessary may be carried out by any other suitable method. Choices of N-debenzylating agent and the conditions for using them are fairly wide [18][19][20][21][22][23][24][25], which on the whole makes the proposed method practically universal and enables it to be recommended as a practical method.…”

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confidence: 99%

4-Hydroxyquinol-2-ones. 86. Synthesis of Methyl (Ethyl) Esters of 1-Substituted 4-Amino-2-oxoquinoline-3-carboxylic Acids

Украинец

Сидоренко

Gorokhova

2005

Chem Heterocycl Compd

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Esters of 1-substituted 4-amino-2-oxoquinoline-3-carboxylic acids 1 are of interest as potentially biologically active substances and also as a basis for further chemical conversions with an adequately broad synthetic potential.The usual method of obtaining compounds of this family comprises acylation of anthranilonitrile 2 with the acid chloride of an appropriate acid, containing a fairly reactive methylene group, with subsequent closure of the 4-aminoquinoline ring under the action of basic catalysts [2,3]. This method gives good results in the synthesis of 3-alkoxycarbonyl-1H-4-amino-2-oxoquinolines 3 [4] and, in principle, may be used for obtaining 1-N-alkyl derivatives 1 (Scheme 1, method A). Regretably alkylation of anthranilonitrile 2 does not occur quantitatively and the N-alkyl derivatives obtained always contain contamination by the starting material, effective elimination of which is only possible by chromatography (especially in the case of the lower N-alkyl substituents). Using the available N-alkylanthranilic acids in the synthesis of anthranilonitriles 4 [5] may exclude chromatographic purification, but such a modification introduces several additional stages, esterification, amidation in an autoclave, dehydration of the amide, and removal of the N-protecting group [2,3], which is not always justified by far.A second possible variant for obtaining esters of 1-substituted 4-amino-2-oxoquinoline-3-carboxylic acids 1 is the alkylation of the previously isolated 1H-derivatives 3 (method B). As a result of lactam-lactim, enamine-imine, and keto-enol tautomerism for esters 3 it is possible that five tautomeric forms exist (Scheme 2), in which both nitrogen atoms, the oxygen of the 2-C=O group, or the carbon atom at position 3 of the quinoline ring may potentially be nucleophilic centers.We noted previously [4] that the properties of the 4-amino group in esters 3, judging by the chemical shift of its protons in the 1 H NMR spectrum (8.3 ppm), are far closer to an amide than to a normal amine (for example, for anilines the mean value is ~4 ppm [6]). It is also known that in 1H-4-amino-2-oxo-3-phenylquinolines alkylation of the 4-amino group (chemical shift 5.9 ppm) is successfully effected only in the _______ * For Part 85 see [1].

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confidence: 99%

4-Hydroxyquinol-2-ones. 86. Synthesis of Methyl (Ethyl) Esters of 1-Substituted 4-Amino-2-oxoquinoline-3-carboxylic Acids

Украинец

Сидоренко

Gorokhova

2005

Chem Heterocycl Compd

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“…As a lot of natural products and pharmaceuticals contain NHfree indole motifs, we demonstrated that the N-benzyl substituent of indole derivative 14 could be deprotected (Scheme 5). We used slightly modified conditions described by Deaton-Rewolinski, 31 namely large excess of tBuOK (5 equiv.) in DMSO at 60 ºC under oxygen bubbling.…”

Section: Resultsmentioning

confidence: 99%

Palladium-catalyzed direct desulfitative C2 arylations of 3-halo-N-protected indoles using (hetero)arenesulfonyl chlorides

et al. 2016

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. Palladium-catalyzed direct desulfitative C2 arylations of 3-halo-: N -protected indoles using (hetero)arenesulfonyl chlorides. Organic and Biomolecular Chemistry, Royal Society of Chemistry, 2016, 14 (21) The direct arylation of N-protected 3-haloindole derivatives with benzenesulfonyl chlorides as coupling partners using 5 mol% of bis(acetonitrile)dichloropalladium(II) catalyst and lithium carbonate as base in 1,4-dioxane was investigated. We demonstrated that both iodo and chloro substituents at indolyl C3 position act as temporary blocking groups to allow the formation of 2-arylindoles through a direct desulfitative arylation, followed by in-situ dehalogenation. While, from 3-bromoindole derivatives, 2-aryl-3-bromoindoles were obtained without debromination, and could be converted into 2,3-diarylindoles through a second palladium coupling. which are both of interest as potential intermediates in the synthesis of bioactive molecules.

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“…Some nucleophiles do not attack the heterocyclic ring carbon atoms but instead the substituent linked to nitrogen with subsequent N-deprotection, for instance dequaternization (pyrazolium salts) [4] or debenzylation (pyrazoles and indazoles) [333].…”

Section: Reactions With Nucleophilic Reagentsmentioning

confidence: 99%