Facile syntheses of 3,4-disubstituted pyrroline nitroxides and their further synthetic applications

Lithiation of an alfa,beta-unsaturated pyrroline nitroxide ester with LTMP at the beta-carbon followed by treatment with electrophiles led to a new series of 3,4-disubstituted pyrroline nitroxides, which could be used as valuable paramagnetic building blocks. The new compounds were tested in Sonogashira and Stille cross coupling reactions, which offered methyl 1-oxyl-4-substituted-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-carboxylate radicals for new C-C bond formation in poor to moderate yields. The reaction of an alfa,beta-unsaturated pyrroline nitroxide ester with methyl chloroformate generated diester 2b; the partial hydrolysis product of this reaction was shown to be a key compound for the synthesis of paramagnetic uracil derivative 10

SYNTHESIS OF NEW PYRROLINE NITROXIDES WITH ETHYNYL FUNCTIONAL GROUP

3-Substituted and 3,4-disubstituted pyrroline nitroxides containing an ethynyl group or two ethynyl groups were achieved by the reaction of a paramagnetic aldehydes with dimethyl (1-diazo-2-oxopropyl)phosphonate (Bestmann–Ohira reagent). The new compounds containing an ethynyl group were found to be useful building blocks in Sonogashira coupling, cyclization, and cycloaddition reactions producing potentially “azido-specific” cross-linking spin labels, paramagnetic ligands, and polyradical scaffold

Új, 3,4-diszubsztituált pirrolin nitroxidok szintézise és alkalmazása

A Pécsi Tudományegyetem Szerves és Gyógyszerkémiai Intézetében csaknem 60 éve végeznek tudományos kutatómunkát a heterociklusos szerves vegyületek területén. Az 1970-es években Dr. Hideg Kálmán a néhai Prof. Tigyi József akadémikus vezette Biofizikai Intézetben kezdett el foglalkozni stabilis nitroxid szabad gyökök szintézisével. Eleinte ezek a vegyületek a helyi biofizikai kutatások igényeit elégítették ki, majd később a nemzetközi kapcsolatok kiszélesedésével, az új alkalmazási területek megjelenésével az előállított vegyületek száma jelentősen növekedett. A Pécsi Tudományegyetem Biofizikai Intézetében majd a Központi Kutató Laboratóriumban néhai Belágyi József professzor úr és munkatársai foglalkoztak EPR spektroszkópiával

N-Vinylation of Imidazole and Benzimidazole with a Paramagnetic Vinyl Bromide

An N-vinylation of imidazole and benzimidazole with a paramagnetic vinyl bromide was investigated. Among the tested procedures, Pd-catalyzed reaction was the most powerful one. The N-vinylation of 2-aminobenzimidazole with a β-bromo-α,β-unsaturated pyrroline nitroxide aldehyde offered 1,1,3,3-tetramethyl-1H-benzimidazo[1,2-a]pyrrolo[3,4-e]pyrimidin-2(3H)-yloxyl radical and the corresponding non-cyclized Schiff base. The reaction of a β-bromo-α,β-unsaturated pyrroline nitroxide aldehyde with imidazole gave β-imidazo-α,β-unsaturated pyrroline nitroxide aldehyde, which was reduced to the alcohol and converted to an unstable allyl chloride

N-Vinylation of Imidazole and Benzimidazole with a Paramagnetic Vinyl Bromide

An N-vinylation of imidazole and benzimidazole with a paramagnetic vinyl bromide was investigated. Among the tested procedures, Pd-catalyzed reaction was the most powerful one. The N-vinylation of 2-aminobenzimidazole with a β-bromo-α,β-unsaturated pyrroline nitroxide aldehyde offered 1,1,3,3-tetramethyl-1H-benzimidazo[1,2-a]pyrrolo[3,4-e]pyrimidin-2(3H)-yloxyl radical and the corresponding non-cyclized Schiff base. The reaction of a β-bromo-α,β-unsaturated pyrroline nitroxide aldehyde with imidazole gave β-imidazo-α,β-unsaturated pyrroline nitroxide aldehyde, which was reduced to the alcohol and converted to an unstable allyl chloride

Palladium- and/or Copper-Catalyzed Cross-Coupling Reactions of Paramagnetic Vinyl Bromides and Iodides

A series of new 3-substituted-4-iodo-(2,2,5,5-tetramethyl- 2,5-dihydro-1H-pyrrol-1-yl)oxidanyl compounds is synthesized to achieve NH2- and SH-specific spin labels. The new vinyl iodides are tested in Sonogashira and Buchwald–Hartwig cross-coupling reactions to produce a paramagnetic β-amino acid ester, pyrroline nitroxide-condensed heterocycles, including a paramagnetic α,α′-dipyridyl ligand and a spin-labeled sulfonamide