The Use of Chromatographic and Mass Spectrometric Methods in the Preparation of Hydroxyl-containing Derivatives of pyrrolo[3,2,1-ij]quinolines

Abstract

More than fifty years ago, an active search began for substances with antiradical and antioxidant activity, which play a key role in protecting various materials and living organisms from oxidative degradation. Antioxidant activity was discovered quite a long time ago in 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline, its hydrogenated analogue, 6-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline, and their derivatives. Furthermore, these compounds have been shown to exhibit a broad spectrum of biological activity. We have found that substituted hydroxyhydroquinolines have growth-regulating activity for ornamental and agricultural plants, exhibit hepato- and neuroprotective activity, and their hybrid derivatives containing a tricyclic fragment of pyrrolo[3,2,1-ij]quinoline acylated at the hydroxyl group have anticoagulant activity against blood coagulation factor Xa. In this regard, the search for new routes to the production of hybrid compounds in the series of hydroxyl derivatives of pyrrolo[3,2,1-ij]quinolines is relevant. To this end, in this study, hydroxyl-containing substituted pyrrolo[3,2,1-ij]quinolines, including previously undescribed ones, were prepared using chromatographic methods and a mass spectrometric study of their structures was conducted. We previously demonstrated that the reaction of hydroxyl derivatives of hydroquinolines with oxalyl chloride under reflux in toluene can proceed as N,O-, N,C-, or N,N-diacylation. Thin-layer chromatography analysis of the reaction mixture revealed that the interaction of both 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline and 6-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline with oxalyl chloride in refluxing toluene results in the formation of a mixture of two products in a ratio of 7:1 and 4:1, respectively. Using column chromatography, we were able to separate the resulting mixtures and isolate individual compounds. It was established that the main products were completely identical in melting point, chromatographic behavior, and spectral characteristics to the 8-hydroxypyrrolo[3,2,1-ij]quinoline-1,2-diones we had previously synthesized. The by-products were assigned the structures of 4,4,6-trimethyl-1,2-dioxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-8-yl (6-hydroxy-2,2,4-trimethylquinolin-1(2H)-yl)(oxo)acetate and 4,4,6-trimethyl-1,2-dioxo-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-8-yl (6-hydroxy-2,2,4-trimethyl-3,4-dihydroquinolin-1(2H)-yl)(oxo)acetate based on a combination of 1H NMR, HPLC-MS, and mass spectrometry data. The mass spectrometric behavior of the obtained compounds under electron impact was studied, and the fragmentation nature of their molecular ions was determined.