Reaction of α-KetoketeneS,N-Acetals with Hydroxylamine: A Facile General Route to 5-Aryl-3-(N-arylamino,N-alkylamino, orN-azacycloalkyl)-isoxazoles

Rahman, A.; Vishwakarma, Jai N.; Yadav, Rajesh; Ila, H.; Junjappa, H.

doi:10.1055/s-1984-30793

Cited by 20 publications

(7 citation statements)

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“…Their use as versatile intermediates in organic synthesis is well recognized due to the presence of two electrophilic and three nucleophilic reactive sites, which can be exploited in a regioselective manner 20,21. Although isoxazole derivatives have been synthesized from S,S‐/N,S‐acetals22a–22e and β‐oxo esters,22f so far, to the best of our knowledge, there is no report on the synthesis of isoxazoles from β‐oxo dithioesters. Therefore, we set out to explore the feasibility of β‐oxo dithioesters as 1,3‐dielectrophilic synthons to access isoxazoles.…”

Section: Resultsmentioning

confidence: 99%

One‐Pot Three‐Component Heteroannulation of β‐Oxo Dithioesters, Amines and Hydroxylamine: Regioselective, Facile and Straightforward Entry to 5‐Substituted 3‐Aminoisoxazoles

Samai¹,

Chanda²,

Ila³

et al. 2013

Eur J Org Chem

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An efficient and highly regioselective one‐pot three‐component synthesis of previously inaccessible and synthetically demanding 3‐(cycloalkyl/alkyl/arylamino)‐5‐aryl/alkylisoxazoles has been achieved by the cyclocondensation of β‐oxo dithioesters, amines and hydroxylamine in ethanol at reflux. This transformation proceeds via an in situ generated β‐oxothioamide by the reaction of the β‐oxo dithioester and amine, which undergoes nucleophilic attack by hydroxylamine followed by intramolecular cyclization with the oxo functionality and subsequent dehydration to give 5‐substituted 3‐aminoisoxazoles as a single regioisomer in good yields. Furthermore, the mechanism of the reaction has been established experimentally and shown to be in agreement with the hard and soft (Lewis) acid and base (HSAB) theory.

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Section: Resultsmentioning

confidence: 99%

One‐Pot Three‐Component Heteroannulation of β‐Oxo Dithioesters, Amines and Hydroxylamine: Regioselective, Facile and Straightforward Entry to 5‐Substituted 3‐Aminoisoxazoles

Samai¹,

Chanda²,

Ila³

et al. 2013

Eur J Org Chem

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“…An alternate highly regioselective route to 5-(substituted-amino)pyrazoles 36, 37, and 39 was achieved following a modified literature procedure. 25 As shown in Scheme 8, the displacement of one methylthio group of the α-oxoketene dithioacetal 75 26,27 by the appropriate amine in the presence of acetic acid in ethanol afforded the N,Sacetals 76a-c, which were useful three-carbon 1,3-electrophiles. 28 Cyclocondensation with hydrazine 56d in refluxing ethanol, gave access to 5-(substituted-amino)pyrazoles 36, 37, and 39.…”

Section: ■ Introductionmentioning

confidence: 99%

Antitubercular 2-Pyrazolylpyrimidinones: Structure–Activity Relationship and Mode-of-Action Studies

et al. 2021

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Phenotypic screening of a Medicines for Malaria Venture compound library against Mycobacterium tuberculosis (Mtb) identified a cluster of pan-active 2-pyrazolylpyrimidinones. The biology triage of these actives using various tool strains of Mtb suggested a novel mechanism of action. The compounds were bactericidal against replicating Mtb and retained potency against clinical isolates of Mtb. Although selected MmpL3 mutant strains of Mtb showed resistance to these compounds, there was no shift in the minimum inhibitory concentration (MIC) against a mmpL3 hypomorph, suggesting mutations in MmpL3 as a possible resistance mechanism for the compounds but not necessarily as the target. RNA transcriptional profiling and the checkerboard board 2D-MIC assay in the presence of varying concentrations of ferrous salt indicated perturbation of the Fe-homeostasis by the compounds. Structure–activity relationship studies identified potent compounds with good physicochemical properties and in vitro microsomal metabolic stability with moderate selectivity over cytotoxicity against mammalian cell lines.

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“…As a result of this they are desirable starting materials for the synthesis of nitrogencontaining heterocycles, derivatives of pyrimidine, pyrrole, pyridine, isoxazole, and quinoline [1][2][3][4][5]. In reactions with nucleophiles these substrates react at two reaction centers, at the carbonyl group and at C-3 [5]. The relative ease of carrying out such heterocyclizations is caused by the good nucleofugicity of the alkylthio group of 3-alkylthio-3-(R-amino)-1-aryl-propenones.…”

mentioning

confidence: 99%

“…In addition the presence of competing reaction centers may lead to nonselectivity in the execution of reactions of 3-alkylthio-3-(R-amino)-1-aryl-propenones with unsymmetrical dinucleophiles. It should be mentioned that, with the exception of [5], no investigations have been carried out in this area. _______ *Deceased.…”

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confidence: 99%

Heterocyclization of 3-(R-amino)-3-methylthio-1-phenylpropenones and 5-benzoyl-6-methylthio-1,2-dihydropyridin-2-ones with 1,2- and 1,3-dinucleophilic reagents

Britsun

Pikun

Ryabitskii

et al. 2011

Chem Heterocycl Comp

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Keywords: 1-alkyl-5-benzoyl-3-ethoxycarbonyl-6-methylthio-1,2-dihydropyridin-2-ones, 6-amino-5-benzoyl-3-ethoxycarbonyl-1-methyl-1,2-dihydropyridin-2-one, 3-(R-amino)-3-methylthio-1-phenylpropenones, 1-R 1 -5-(R-amino)-3-phenylpyrazoles, benzimidazo[1,2-a]pyridines, benzimidazo[1,2-a]-pyrimidines, 6,7-dihydro-2H-pyrazolo [3,4-b]pyridines, 1,2,4-triazole, [1,2,4]triazolo[4,3-b]pyridazines, heterocyclization, [3+2] and [3+3] cyclocondensations.3-Alkylthio-3-(R-amino)-1-arylpropenones may react both with electrophilic and with nucleophilic and polycentered reagents. As a result of this they are desirable starting materials for the synthesis of nitrogencontaining heterocycles, derivatives of pyrimidine, pyrrole, pyridine, isoxazole, and quinoline [1][2][3][4][5]. In reactions with nucleophiles these substrates react at two reaction centers, at the carbonyl group and at C-3 [5]. The relative ease of carrying out such heterocyclizations is caused by the good nucleofugicity of the alkylthio group of 3-alkylthio-3-(R-amino)-1-aryl-propenones. In addition the presence of competing reaction centers may lead to nonselectivity in the execution of reactions of 3-alkylthio-3-(R-amino)-1-aryl-propenones with unsymmetrical dinucleophiles. It should be mentioned that, with the exception of [5], no investigations have been carried out in this area.

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Reaction of α-KetoketeneS,N-Acetals with Hydroxylamine: A Facile General Route to 5-Aryl-3-(N-arylamino,N-alkylamino, orN-azacycloalkyl)-isoxazoles

Cited by 20 publications

References 0 publications

One‐Pot Three‐Component Heteroannulation of β‐Oxo Dithioesters, Amines and Hydroxylamine: Regioselective, Facile and Straightforward Entry to 5‐Substituted 3‐Aminoisoxazoles

One‐Pot Three‐Component Heteroannulation of β‐Oxo Dithioesters, Amines and Hydroxylamine: Regioselective, Facile and Straightforward Entry to 5‐Substituted 3‐Aminoisoxazoles

Antitubercular 2-Pyrazolylpyrimidinones: Structure–Activity Relationship and Mode-of-Action Studies

Heterocyclization of 3-(R-amino)-3-methylthio-1-phenylpropenones and 5-benzoyl-6-methylthio-1,2-dihydropyridin-2-ones with 1,2- and 1,3-dinucleophilic reagents

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