Work

Can Water Trigger Room‐Temperature Formation of Benzofuran‐2( 3H )‐one Scaffolds From Vinyldiazene Derivatives? Computational Insights Into an Unusual Cyclization

Year: 2025

Type: article

Abstract: ABSTRACT Access to benzofuran‐2(3H)‐one derivatives from readily available substrates under mild conditions is crucial in the pharmaceutical and plastics industries. We identified (Z)‐3‐(2‐phenylhydrazineylidene)benzofuran‐2(3H)‐one (P) during the recrystallization of (E)‐2‐(2,2‐dichloro‐1‐(phenyldiazenyl)vinyl)phenol using a 96% ethanol solution. The mechanism of the unexpected substrate conversion leading to P is investigated using density functional calculations. The computations revealed that ethanol is required to initiate the reaction via TS1E, which involves a concerted deprotonation of ethanol by the basic diaza group of the substrate and an ethoxy group attacking the electrophilic center (Cl2C), with an energy barrier of 28.3 kcal/mol. The resulting intermediate (I1E) is calculated to be unstable and can yield a cyclic chloroacetal adduct with a lower energy barrier of 2.2 kcal/mol via the ring‐closure transition state (TS2E). In the absence of water, the next steps are impossible because water is required to cleave the ether bond, yielding P. A small amount of water (4% of the recrystallization solvent) can promote further transformation of I2E via the transition states TS3E (∆G‡ = 11.1 kcal/mol) and TS4E (∆G‡ = 10.5 kcal/mol). A comparison of the ethanol/water‐ and only water‐promoted free energy profiles shows that the presence of ethanol is crucial for lowering the energy barriers (by about 5 kcal/mol) for the initial two steps leading to the cyclic chloroacetal (I2E), whereas water is then required to initiate product formation.

Source: Journal of Computational Chemistry

DOI: 10.1002/jcc.70102

Authors: Ulviyya Askerova, Yusif Abdullayev, Namiq Shikhaliyev, Avtandil Talybov, Jochen Autschbach

Institutions: Baku State University, Azerbaijan National Academy of Sciences, Allen University, Baku Engineering University, University at Buffalo, State University of New York

Language: English

Topic: Organic Chemistry Cycloaddition Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: bronze

Funders: National Science Foundation, University at Buffalo, Division of Chemistry

Awards: Exploring Response Properties of Molecules and Extended Systems Using Theoretical Methods, G7504169866