A Useful Synthetic Route to N-Nonsubstituted Succinimides via Light-Induced Degradation of Metallocarbonyl Complexes

Abstract

Succinimides are among the most studied compounds due to their wide profile of biological activities. It is well-known that succinimides undergo ring-opening reactions under alkaline conditions. This feature limits the formation of 3-substituted succinimides from maleimides by an oxa-Michael reaction, for which basic conditions are required. Herein, we report the synthesis, characterization, and crystal structure of metallocarbonyl (Fe, Ru) complexes bearing 3-substituted succinimide ligands. These complexes were obtained in oxa-Michael reactions of CpM­(CO)2(η1-maleimidato) (M = Fe, Ru) with alcohols (MeOH, EtOH) in the presence of K2CO3. During the crystallographic studies of an iron complex bearing the 3-methoxysuccinimide ligand, we also identified unexpected crystals of free 3-methoxysuccinimide. We performed some additional experiments and theoretical calculations to determine the mechanism of formation of the obtained N-nonsubstituted succinimide. We demonstrate that 3-methoxysuccinimide resulted from light-induced degradation of CpFe­(CO)2(η1-3-methoxysuccinimidato). On the basis of these findings, we propose an indirect route leading to 3-substituted succinimides starting from maleimide via the light-induced degradation of iron metallocarbonyl succinimidato complexes. The proposed methodology prevents ring opening of succinimide under alkaline conditions and gives N-nonsubstituted succinimide products. To confirm the effectiveness of the described method, CpFe­(CO)2(η1-maleimidato) was allowed to react with several aliphatic alcohols and phenol, affording the oxa-Michael reaction products in the case of primary alcohols. The irradiation of the obtained compounds with daylight gave the N-nonsubstituted 3-alkoxysuccinimides.

Cytotoxicity of piano‐stool ruthenium cyclopentadienyl complexes bearing different imidato ligands

“…Complexes 2 CpRu (CO) 2 ( η 1 ‐3‐methoxysuccinimidato) and 3 CpRu (CO) 2 ( η 1 ‐3‐ethoxysuccinimidato) were synthesized in Oxa‐Michael reaction of complex 1 with methanol or ethanol respectively in the presence of K 2 CO 3 according to the previously published method. [ 18,19 ]…”

“…Some of us have already reported that the irradiation of iron metallocarbonyl complexes led to degradation of complex and released of CO and free imide. [ 19,36 ]…”

“…[17] Alkoxysuccinimide complexes 2 (η 5 -cyclopentadienyl)Ru (CO) 2 -N-methoxysuccinimidato and 3 (η 5 -cyclopentadienyl)Ru (CO) 2 -N-ethoxysuccinimidato were synthesized as previously described. [18,19] Chromatographic purifications were performed on silica gel Merck 60 (230-400 mesh). Infrared (IR) spectra were recorded in KBr on an Fourier Transform InfraRed (FT-IR) NEXUS (Thermo Nicolet) spectrometer.…”

“…Complexes 2 CpRu (CO) 2 (η 1 -3-methoxysuccinimidato) and 3 CpRu (CO) 2 (η 1 -3-ethoxysuccinimidato) were synthesized in Oxa-Michael reaction of complex 1 with methanol or ethanol respectively in the presence of K 2 CO 3 according to the previously published method. [18,19] S C H E M E 1 Synthesis of metallocarbonyl complex 4 F I G U R E 2 Molecular structure of 4 with atom labeling scheme. Displacement ellipsoid are drawn in 40% probability level…”

“…Some of us have already reported that the irradiation of iron metallocarbonyl complexes led to degradation of complex and released of CO and free imide. [19,36] We also determined the effect of free imidesmaleimide, succinimide, and their N-substituted derivatives (Figure S7) on the viability of PBMCs and HL-60 cells.…”