N‐Allyl‐N‐ferrocenylmethylamines and ansa‐Ferrocenylmethylamines: Synthesis, Structure, and Biological Evaluation

• Published in: European journal of inorganic chemistry Vol. 2022; no. 10
• Main Authors: Mazur, Maria, Ziemkiewicz, Kamil, Rawiak, Karol, Kisiel, Kacper, Wińska, Patrycja, Deresz, Krystyna, Jarzembska, Katarzyna N., Buchowicz, Włodzimierz
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 08.04.2022
• Subjects: Aldehydes; Anticancer properties; Antitumor agents; Bioinorganic chemistry; Biological activity; Crystal structure; Crystals; Ferrocenes; Inorganic chemistry; Nitrogen; Structure elucidation
• ISSN: 1434-1948; 1099-0682
• DOI: 10.1002/ejic.202101098

Reductive aminations of ferrocenecarboxaldehyde, ansa‐ferrocenecarboxaldehyde, and 1,1′‐ferrocene‐dicarboxaldehyde with allylamine, N‐allylmethylamine, or N‐allylaniline were investigated. In the case of the dialdehyde only one formyl group effectively reacted with N‐allylmethylamine or N‐allylaniline, thus providing a simple route to aminomethyl aldehydes and aminomethyl alcohol. 2‐Aza‐ansa[3] ferrocene was also obtained by reacting the dialdehyde with one equivalent of allylamine and subsequent deprotection of the nitrogen atom. The isolated N‐allyl ferrocene derivatives were completely characterized by spectroscopic techniques, whereas crystal structures of four representative compounds were determined using single‐crystal X‐ray diffraction. MTT assays showed that these simple N‐allyl ferrocene derivatives display anticancer activity (MCF‐7, A‐549 and PC‐3 cell lines) in the micromolar range. Reactions of ferrocenecarboxaldehydes with allylamine, N‐allylmethylamine, or N‐allylaniline provided N‐allylmethyl‐functionalized ferrocenes, including N‐allyl aldehydes and N‐allyl alcohols. 2‐Aza‐ansa[3] ferrocene was also obtained by reductive amination/deprotection sequence. MTT assays showed that these simple N‐allyl ferrocene derivatives display anticancer activity (MCF‐7, A‐549, and PC‐3 cell lines) in the micromolar range.