Towards greener synthesis of substituted 3-aminophthalates starting from 2h-pyran-2-ones via Diels–Alder reaction of acetylenedicarboxylates

Fendre, Dominik (author), Lukšič, Miha (author), Kranjc, Krištof (author)

The aim of this work was to prepare a large set of variously substituted 3-aminophthalates starting from substituted 3-acylamino-2H-pyran-2-ones acting as dienes in Diels–Alder reactions with dialkyl acetylenedicarboxylates having the role of dienophiles. These thermally allowed [4+2] cycloadditions were taking place with normal electron demand due to rather electron-deficient dienophiles and relatively electron-rich dienes; however, they still required quite harsh reaction conditions: heating in closed vessels at 190 °C for up to 17 h was sufficient in most cases (albeit for a few reactions the time needed was up to 58 h) to achieve conversions above 95%. Such conditions, unfortunately, necessitated the use of a larger excess of dienophiles (as undesired polymerization takes place concomitantly); nevertheless, the straightforward isolation procedures enabled access to the target compounds in moderate to high yields (average yield 56%). All products were characterized by standard analytical and spectroscopic methods. With the goal of changing the reaction conditions to be more environmentally friendly, we investigated the effect of various solvents (water, n-butanol, butyl acetate, xylene, para-cymene, n-nonane, etc.) and the temperature applied (130–190 °C) on the conversion. We found that higher temperatures are necessary in most cases (except for the most reactive 2H-pyran-2-ones) regardless of the solvent used. Relative reactivity was determined for both sets of reactants and the experimentally obtained data show good agreement with the computational results.

• Language: English
• Keywords: heterocycles, 2H-pyran-2-ones, [4+2] cycloaddition, phthalic esters, anilines
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 28 str.
• Numbering: Vol. 30, iss. 11, arti. 2271
• PID: 20.500.12556/RUL-171268
• UDC: 577.81
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules30112271
• COBISS.SI-ID: 237203971
• Publication date in RUL: 21.08.2025

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: heterocikli, 2H-piran-2-oni, [4+2] cikloadicija, estri ftalne kisline, anilini