Antihypertensive Agents. III.1 3-Hydroxy-3-phenylphthalimidines

Topliss, John G.; Konzelman, Leroy M.; Sperber, Nathan; Roth, F

doi:10.1021/jm00334a012

Cited by 30 publications

(9 citation statements)

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“…Initially, equimolar 1aa and 2aa were heated directly without any catalysts or additives in various solvents at 100°C in an oil bath for 5 h. Interestingly, the reaction results were largely influenced by the solvent used. The reactions in 1,2-dimethoxyethane, THF, 1,4-dioxane, CH 3 CN, DMSO, DMF, EtOH and H 2 O (entries 2-3, [5][6][8][9][10][11] selectively gave the 3-hydroxyisoindolinone 3aa as the single product in good to high yields, while reactions in toluene, DCE and CH 3 NO 2 (entries 1, 4, 7) provided a mixture of 3-hydroxyisoindolinone 3aa and 3-methyleneiso- Table 1. Survey of the reaction conditions of the divergent cascade reactions between 1aa and 2aa.…”

Section: Resultsmentioning

confidence: 99%

“…[4] In particular, the 3-hydroxyisoindolinones, 3-methyleneisoindolinones, and isoindolinone-fused tetracyclic ring system of 5,6-dihydroisoindolo [1,2-a]isoquinolin-8(12bH)-ones form three important classes of compounds since they are widely found in natural products and pharmaceutical agents (Figure 1). [5][6][7][8][9][10] Therefore, methods for the assembly of these three architectures have captured considerable attention and tremendous efforts have been made to synthesize these heterocyclic compounds. First of all, the synthesis of 3-hydroxyisoindolinones has been well studied and established.…”

Section: Introductionmentioning

confidence: 99%

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Metal‐Free Selective and Diverse Synthesis of Three Distinct Sets of Isoindolinones from 2‐Alkynylbenzoic Acids and Amines

Jia

Zhang

et al. 2020

Eur J Org Chem

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The metal‐free selective and diverse synthesis of three distinct sets of isoindolinones from 2‐alkynylbenzoic acids and amines has been achieved in a reaction‐condition‐controlled manner. This method exhibits valuable advantageous features such as available starting materials, broad substrate scope, excellent selectivity, good to high yields, good functional group tolerance, simple operation, high bond‐forming efficiency, and step economy, thus providing a convenient and efficient access to a variety of heterocyclic compounds incorporating the bioactive isoindolinone motif.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metal‐Free Selective and Diverse Synthesis of Three Distinct Sets of Isoindolinones from 2‐Alkynylbenzoic Acids and Amines

Jia

Zhang

et al. 2020

Eur J Org Chem

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“…This isoindolinone scaffold has been shown to produce antitumor effects by inhibiting MDM2-p53 interactions, 18 as well as serving as the antihypertensive agent Chlortalidone. 19 This heterocyclic core can be found in several natural compounds. 20 Furthermore, a variety of postsynthetic modifications of the core hydroxyisoindoline structure are possible (Scheme 4) including enantioselective transformations mediated by chiral phosphoric acids.…”

Section: Methodsmentioning

confidence: 99%

Diverting Radical-Anionic C-H Amidation to a C-N/C-O Cascade for the Construction of Hydroxyisoindolines from Unprotected Amides

Elliott¹,

Gomes²,

Evoniuk³

et al. 2019

Preprint

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An intramolecular C(sp3)-H amidation proceeds in the presence of t-BuOK, molecular oxygen, and DMF. The success of this reaction hinges on the deprotonation of a mildly acidic N-H bond and selective radical activation of a benzylic C(sp3)-H bond towards hydrogen atom transfer (HAT). DFT calculations suggest a thermodynamically favorable sequence of steps mediated by the generation of a radical-anion intermediate. As this intermediate starts to form a two-centered/three-electron (2c,3e)C-N bond, the extra electron is “ejected” into the π*-orbital of the aromatic core. The resulting cyclic radical-anion is readily oxidized by molecular oxygen to forge the C-N bond of the product. The transformation of a relatively weak reductant into a stronger reductant (i.e., “reductant upconversion”) allows one to use mild oxidants such as molecular oxygen. In contrast, the second stage of NH/CH activation forms a highly stabilized radical-anion intermediate incapable of electron transfer to molecular oxygen. Hence, the oxidation is impossible and an alternative reaction path opens via coupling between the radical anion intermediate and either superoxide or hydroperoxide radical. The hydroperoxide intermediate transforms into the final hydroxyisoindoline products under basic conditions. The use of TEMPO as an additive was found to activate less reactive amides. The combination of experimental and computational data outlines a conceptually new mechanism for the conversion of unprotected amides into hydroxyisoindolines proceeding as a sequence of C-H amidation and C-H oxidation.

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“…In addition, the development of catalytic carbonylation reactions for the synthesis of biologically active heterocyclic scaffolds has emerged as an efficient protocol in recent decades . Isoindolinone frameworks are frequently found in many bioactive molecules and drug candidates exhibiting HIV‐1 reverse transcriptase inhibitors, diuretics, anti‐hypertensives, dopamine D4 receptor antagonists, and benzodiazepine receptors agonist for the treatment of anxiety (Figure ) ,…”

Section: Figurementioning

confidence: 99%

Supported Palladium Nanoparticles that Catalyze Aminocarbonylation of Aryl Halides with Amines using Oxalic Acid as a Sustainable CO Source

Reddy

Ram

Kumar

et al. 2019

Chemistry A European J

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Polystyrene‐supported palladium (Pd@PS) nanoparticles (NPs) have been used to catalyze the aminocarbonylation of aryl halides with amines using oxalic acid as a CO source for the first‐time for the synthesis of amides. Furthermore, o‐iodoacetophenones participated in amidation and cyclization reactions to give isoindolinones in a single step following a concerted approach. Oxalic acid has been used as a safe, environmentally benign and operationally simple ex situ sustainable CO source under double‐layer‐vial (DLV) system for different aminocarbonylation reactions. Catalyst stability under a CO environment is a challenging task, however, Pd@PS was found to be recyclable and applicable for a vast substrate scope avoiding regeneration steps. Easy handling of oxalic acid, additive and base‐free CO generation, catalyst stability and effortless catalyst separation from the reaction mixture by filtration and introduce of DLV are the added advantages to make the overall process a sustainable approach.

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Antihypertensive Agents. III.¹ 3-Hydroxy-3-phenylphthalimidines

Cited by 30 publications

References 1 publication

Metal‐Free Selective and Diverse Synthesis of Three Distinct Sets of Isoindolinones from 2‐Alkynylbenzoic Acids and Amines

Metal‐Free Selective and Diverse Synthesis of Three Distinct Sets of Isoindolinones from 2‐Alkynylbenzoic Acids and Amines

Diverting Radical-Anionic C-H Amidation to a C-N/C-O Cascade for the Construction of Hydroxyisoindolines from Unprotected Amides

Supported Palladium Nanoparticles that Catalyze Aminocarbonylation of Aryl Halides with Amines using Oxalic Acid as a Sustainable CO Source

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