4,6-Dimetoksibenzofuran-7-Karbaldehitlerin Dakin Oksidasyonu: Benzofuran-7-ol Bileşiklerinin Sentezi

Year 2025, Volume: 25 Issue: 6, 1308 - 1315

Hakan Kandemir , Tuğçe Nur Uslu Uçar , İbrahim Fazıl Şengül

Abstract

Dakin oksidasyonu ile 4,6-dimetoksibenzofuran-7-karbaldehitlerin 6-metoksi-benzofuran-4,7-kinonlara dönüşümü daha önce tarafımızdan rapor edilmiştir. Bu çalışmada ise, Dakin oksidasyon reaksiyonunda kullanılan hidrojen peroksit (H₂O₂) miktarının reaksiyon üzerindeki etkisi araştırılmıştır. Reaksiyon koşullarının optimize edilmesiyle, başarılı bir şekilde benzofuran-7-ol türevleri elde edilmiştir. Elde edilen sonuçlar, H₂O₂ miktarının ürün seçiciliği üzerindeki etkisini ortaya koymakta ve benzofuran türevlerinin verimli sentez stratejilerinin geliştirilmesine katkı sağlamaktadır. Sentezlenen 4,6-dimetoksibenzofuran-7-ol yapıların karakterizasyonu, ¹H NMR, ¹³C NMR, FT-IR ve kütle spektrum analizleri kullanılarak gerçekleştirilmiştir. Ayrıca, uygun kristal yapıya sahip bileşiklerin yapıları X-ışını kırınım analizi ile de doğrulanmıştır.

Keywords

Heterosiklik , Dakin oksidasyon , Benzofuran

Project Number

122Z598

Dakin Oxidation of 4,6-Dimethoxybenzofuran-7-Carbaldehydes: Synthesis of Benzofuran-7-ols

Abstract

The conversion of 4,6-dimethoxybenzofuran-7-carbaldehydes to the 6-methoxy-benzofuran-4,7-quinones by the Dakin oxidation was reported by us. In the current work, we explored the effect of varying amount of hydrogen peroxide (H₂O₂) on the outcome of the Dakin oxidation reaction. By optimizing the reaction conditions, benzofuran-7-ol derivatives were successfully prepared. The results provide insight into the influence of H₂O₂ quantity on product selectivity, contributing to the development of efficient synthetic strategies for benzofuran derivatives. The structures of the synthesized 4,6-dimethoxy-benzofuran-7-ols were confirmed employing ¹H NMR, ¹³C NMR, FT-IR and mass spectral analyses. Additionally, the structures of compounds with suitable crystalline forms were further confirmed by X-ray diffraction analysis.

Keywords

Heterocyclic , Dakin Oxidation , Benzofuran

Supporting Institution

TUBİTAK

Project Number

122Z598

Thanks

This study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) under the Grant Number 122Z598. The authors thank TUBITAK for their support.

References

• Alamgir M., Mitchell P.S.R., Bowyer P.K., Kumar N., Black D.S.C., 2008. Synthesis of 4,7-indoloquinones from indole-7-carbaldehydes by Dakin oxidation. Tetrahedron, 64, 7136-7142. https://doi.org/10.1016/j.tet.2008.05.107
• Bendi A., Sirija M.R., Bhathiwal A.S., Chinmay, Chauhan V. and Tiwari A., 2024. Exploring the potential therapeutic role of benzofuran derivatives in cancer treatment. J. Mol. Struct., 1317, 139121. https://doi.org/10.1016/j.molstruc.2024.139121
• Black D.SC., Craig D.C. and Rezaie R., 2002. Synthesis of mixed heterocalixarenes from benzofuranyl methanols and activated indoles. Chem Commun., 2(8), 810-811. https://doi.org/10.1039/B200373B
• Ceyhan S.M., Zengin I.N., Bingul M., Sahin H., Boga M., Saglam M.F., Kandemir H. and Sengul I.F., 2024. Indolyl imine compounds as multi-target agents; synthesis, antidiabetic, anticholinesterase, antioxidant activities and molecular modeling. J. Mol. Struct., 1309(4), 138159. https://doi.org/10.1016/j.molstruc.2024.138159
• De la Rosa L.A., Moreno-Escamilla J.O., Rodríguez-García J. and Alvarez-Parrilla E., 2019. Postharvest physiology and biochemistry of fruits and vegetables. In: Yahia EM, Carrillo-Lopez A, editors. Phenolic Compounds, 253-71. Deorha D.S. and Gupta P., 1963. N,N-Dimethylacetamide as an acylating agent. Chem Ber., 97, 616-7. He S.Y., Xiong J., Hu B.L. and Zhang X.G., 2019. Copper-catalyzed tandem cyclization and vinylation for the synthesis of 2-trifluoromethyl benzofurans. J Fluor Chem., 228, 109418. https://doi.org/10.1016/j.jfluchem.2019.109418
• Mercado-Mercado G., de la Rosa L.A. and Alvarez-Parrilla E., 2020. Effect of pectin on the interactions among phenolic compounds determined by antioxidant capacity. J Mol Struct., 1199, 126967. https://doi.org/10.1016/j.molstruc.2019.126967
• Miao Y., Hu Y., Yang J., Liu T., Sun J. and Wang X., 2019. Natural source, bioactivity and synthesis of benzofuran derivatives. RSC Adv., 9(47), 27510-27540. https://doi.org/10.1039/C9RA04917G
• Ojha K., Dubey S., Chandrakar J., Anigo-Minj R., Dehariya R. and Dixit K., 2018. A review on different methods of determination of antioxidant activity assay of herbal plants. Res J Life Sci Bioinf Pharm Chem Sci., 4(6), 707. https://doi.org/10.26479/2018.0406.56
• Sivaraman A., Harmalkar D.S., Kang J., Choi Y. and Lee K., 2019. A protecting group-free divergent synthesis of natural benzofurans via one-pot synthesis of 2-bromo-6-hydroxybenzofurans. Org Biomol Chem., 17(8), 2153-61. https://doi.org/10.1039/C8OB03102A
• Uslu Ucar T.N., İzgi S., Demir E.A., Uzuner S.C, Sengul I.F., Uzuner U. and Kandemir H., 2025. Synthesis of novel benzofuran-4,7-quinones from 4,6-dimethoxybenzofurans specifically targeting breast and lung cancer cells. Monats Chemie., 156, 467-80. https://doi.org/10.1007/s00706-025-03304-w