Acid-catalyzed isomerization of maleic acid to fumaric acid: synthesis and characterization of a biomedically relevant dicarboxylic acid

Muhammad Badrul Huda; Fitra Adi Prayogo

doi:10.34310/jbsh.v3i2.358

Authors

Muhammad Badrul Huda Department of Chemistry, Faculty of Sciences and Mathematics, Universitas Diponegoro, Semarang, Indonesia Author https://orcid.org/0009-0003-0464-5543
Fitra Adi Prayogo Biomedical Sciences Program, Faculty of Nursing and Health Sciences, Universitas Karya Husada Semarang, Indonesia Author https://orcid.org/0000-0003-4354-2654

DOI:

https://doi.org/10.34310/jbsh.v3i2.358

Keywords:

fumaric acid, maleic acid, geometric isomerism, acid-catalyzed isomerization, melting point

Abstract

Background: Fumaric acid (trans-butenedioic acid) is the thermodynamically stable geometric isomer of maleic acid (cis-butenedioic acid). It serves as the parent compound of dimethyl fumarate (DMF), an FDA-approved immunomodulatory agent used for relapsing-remitting multiple sclerosis and moderate-to-severe plaque psoriasis. Laboratory-scale synthesis of fumaric acid from maleic acid via acid-catalyzed isomerization provides a practical route for studying the physicochemical properties of this compound. Objective: This study aimed to synthesize fumaric acid through hydrochloric acid (HCl)-catalyzed isomerization of maleic acid under reflux conditions and to characterize the products by melting point determination and gravimetric yield analysis. Methods: Maleic anhydride (2 g) was hydrated in boiling distilled water (5 mL) to produce maleic acid, which was crystallized by cooling. The filtrate containing dissolved maleic acid was treated with concentrated HCl (2 mL) and refluxed for 15 minutes. Fumaric acid was isolated by ice-bath crystallization and gravity filtration. Both products were characterized by gravimetric yield and melting point analysis. Results: Maleic acid was obtained with a yield of 25.39% (0.6011 g) and a melting point of 139°C, consistent with the literature range (130-139°C). Fumaric acid was obtained with a yield of 34.64% (0.6119 g) and a melting point of 280°C, slightly below the reported literature range (286-302°C), suggesting the presence of minor impurities. Conclusion: The HCl-catalyzed reflux method converted maleic acid to fumaric acid through an addition-rotation-elimination mechanism. The higher melting point of fumaric acid reflects its greater molecular symmetry and stronger intermolecular interactions in the crystal lattice.

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