Insight into the Mechanism of the Pechmann Condensation Reaction Using NMR

Tyndall, Stephen; Wong, Koon Fai; VanAlstine-Parris, Melissa A.

doi:10.1021/acs.joc.5b01802

Cited by 25 publications

(9 citation statements)

References 15 publications

(32 reference statements)

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“…The cinnamic ester derivative was also reported as a side product of the Pechmann condensation. 20 Tyndall and coauthors 36 monitored the reaction between resorcinol (1b) and ethyl 4,4,4trifluoroacetoacetate (2c) using 19 F NMR and 1 H NMR. In this study, iodine was used as catalyst and toluene as solvent.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of C4-substituted coumarins via Pechmann condensation catalyzed by sulfamic acid. Insights into the reaction mechanism by HRMS analysis

Barcellos¹,

Moraes²,

Lenardão³

2021

Arkivoc

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A series of functionalized C4-substituted coumarins were synthesized by exploring the reaction of activated and non-activated phenols and β-ketoesters under solvent-free conditions in the presence of sulfamic acid as a Br∅nsted acid catalyst. Fifteen examples were prepared with moderate to excellent yields (50% to 90%) using 10 mol % of the catalyst. Furthermore, it was possible from the proposed methodology to scale up the synthesis of coumarins to obtain up to 11 g of product. This work also provides a preliminary insight into the reaction mechanism using high-resolution mass spectrometry analysis. The key cinnamic acid derivative intermediate was detected, implying that under the evaluated conditions, the mechanistic pathway starts with an aromatic electrophilic substitution followed by dehydration reaction and intramolecular transesterification.

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Section: Resultsmentioning

confidence: 99%

Synthesis of C4-substituted coumarins via Pechmann condensation catalyzed by sulfamic acid. Insights into the reaction mechanism by HRMS analysis

Barcellos¹,

Moraes²,

Lenardão³

2021

Arkivoc

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show abstract

“…The intermediate rapidly cyclizes through an intramolecular condensation (a S E Ar type reaction) followed by dehydration. However, there are NMR studies that have concluded that the sequence of events is different, i.e., the condensation begins with the activation of the β-keto group (protonation or complexation with a Lewis acid, path B) followed by electrophilic aromatic substitution, cyclization, and final dehydration [69]. It was found that the reaction can be promoted not only by homogenous catalysts, but also by convenient reusable or magnetically recoverable particles [70][71][72] or ionic liquids [73] carrying protic or Lewis acids.…”

Section: Coumarins: Synthesis Structures and Propertiesmentioning

confidence: 99%

Antagonists of Vitamin K—Popular Coumarin Drugs and New Synthetic and Natural Coumarin Derivatives

et al. 2020

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Many natural coumarins and their chemically synthesized analogs and derivatives exert diverse properties, such as anticancer, antioxidant, anti-inflammatory, or anticoagulant, with the latter being of the utmost importance. The widely used warfarin, acenocoumarol, and phenprocoumon exert anticoagulant properties by inhibiting the vitamin K epoxide reductase complex. In this interdisciplinary review, we present biochemical principles of the coagulation processes and possible methods for their tuning based on the use of coumarins. We also summarize chemical methods of synthesis of coumarins and discuss structures and properties of those that have been used for a long time, as well as newly synthesized compounds. Brief information on the clinical use of coumarins and other anticoagulant drugs is given, including the severe effects of overdosing and methods for reversing their action.

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“…The immense interest in the biological and medicinal importance of coumarin derivatives has triggered the development of various catalysts and reactions conditions in this regard. In addition, the mechanism undelaying the Pechmann condensation, which is still controversial, has been discussed in depth by both theoretical and experimental methods [ 9 , 10 , 11 ]. Recently, advances in the synthesis of coumarins via the Pechmann condensation have been extensively reviewed [ 12 ].…”

Section: Synthetic Routes Toward Central 2-pyrone Of 4-arylcoumarimentioning

confidence: 99%

Recent Advances in Synthesis of 4-Arylcoumarins

et al. 2018

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4-Arylcoumarins (4-aryl-2H-1-benzopyran-2-one), also known as neoflavones, comprise a minor subclass of naturally occurring flavonoids. Because of their broad-spectrum biological activities, arylcoumarins have been attracting the attention of the organic and medicinal chemistry communities, and are considered as an important privileged scaffold. Since the development of Pechmann condensation, a classical acid-catalyzed condensation between phenol and β-keto-carboxylic acid, several versatile and efficient synthetic approaches for 4-arylcoumarins have been reported. This review summarizes recent advances in the synthesis of the 4-arylcoumarin scaffold by classifying them based on the final bond-formation type. In particular, synthetic methods executed under mild and highly efficient conditions, such as solvent-free reactions and transition metal catalysis, are highlighted.

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Insight into the Mechanism of the Pechmann Condensation Reaction Using NMR

Cited by 25 publications

References 15 publications

Synthesis of C4-substituted coumarins via Pechmann condensation catalyzed by sulfamic acid. Insights into the reaction mechanism by HRMS analysis

Synthesis of C4-substituted coumarins via Pechmann condensation catalyzed by sulfamic acid. Insights into the reaction mechanism by HRMS analysis

Antagonists of Vitamin K—Popular Coumarin Drugs and New Synthetic and Natural Coumarin Derivatives

Recent Advances in Synthesis of 4-Arylcoumarins

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