The nitration reaction of trichloroethene (1) to main products trichloronitroethene (TCNiE 2, up to 60.8 %, by GC), 1,1,2,2-tetrachloro-1-nitroethane (8, up to 25.1 %, by GC), and 1,2,2-trichloro-2-nitroethyl [chloro(nitro)methylene]azinate (9, up to 8.0 %, by GC) was comprehensively investigated and optimized. Different 1,1-diamino-2-chloro-2-nitroethenes, 2-nitroethoxyguanidines, and rare O-(1,2,2-trichloro-2-nitroethyl) oximes and carbimidoyl halides with unique formulas R–O–N=C(NO2)NRR1 and R–O–N=C(Hal)NRR1, respectively, were obtained from these nitration products in yields up to 91 %. The structure of (E)-morpholino(nitro)methanone O-(1,2,2-trichloro-2-nitroethyl) oxime (19) was proven by single-crystal X-ray diffraction analysis. In addition, the antimicrobial and antifungal activity of the synthesized compounds was examined. Notably, N-(1,2,2-trichloro-2-nitroethoxy)-3,4-dihydroisoquinoline-2(1H)carbimidoyl chloride (27) inhibited the growth of methicillin-resistant and sensitive Staphylococcus aureus with minimum inhibitory concentrations of 1.3 μg mL–1, and reduced the viability of the MCF-7 cancer cell line with an IC50 of 0.2 μg/mL.
Starting from easily accessible 2-chloro-3-(cyclopentyloxy)-7-fluoroquinoxaline 1-oxide, 12 new biologically promising aroylquinoxaline N-oxides were synthesized through carbene-catalyzed aroylation of the chloro nitrone unit with different aromatic aldehydes in the presence of 1,3-dimethylimidazolium iodide as the carbene precursor. The optimized reaction conditions tolerated a broad bandwidth of aldehydes and allowed the synthesis of the corresponding ketones in yields up to 87 %. Studies of their biological activities resulted in interesting specific cytotoxic effects against tumor cell lines.
The readily available and polyfunctionalized 3-chloro-6-fluoroquinoxalin-2(1H)-one 4-oxide, derived from the efficient one-step annulation reaction of 1,1,2-trichloro-2-nitroethene with 4-fluoroaniline, was selectively modified at the chloronitrone and the amide units, leading to more than 30 new quinoxaline derivatives with a unique substitution pattern in good to excellent yields. In addition, the electronic properties of the versatile starting compound were computed by means of density functional theory, which gave a reasonable explanation for its unique reactivity. The antimalarial activity of all hitherto unknown compounds has been investigated.
The unique synthesis of 3-amino-4-nitrothiophenes 2 provides easy access to reference species of a new family of push-pull substituted thiophenes. The chemoselective modification of 2 into suitable derivatives was accomplished by selective S-oxidation of the vinylsulfanyl unit, followed by substitution of the vinylsulfinyl group of 3 by nucleophiles. Dihalothiophenes were formed this way in very good yields. A subsequent selective dehalogenation at the 2, 5 or 2 and 5 positions also proved feasible, and the push-pull unit was untouched. The new 2,5-dihalothiophenes could be interesting monomers for conducting polymers.
A selection of 2-chloro-substituted O-alkylquinoxaline N-oxides, easily accessible by the one-step annulation reaction of 4-fluoroaniline with 1,1,2-trichloro-2-nitroethylene and subsequent O-alkylation, was arylated at the chloronitrone unit in yields up to 96 %. This first efficient Pd-catalyzed Suzuki–Miyaura reaction of chloroquinoxaline N-oxides with arylboronic acids led to new 2-arylquinoxaline N-oxides. The scope and limitations of this arylation reaction were investigated, and the role of some sterically demanding boronic acids in the cross-coupling reaction was evaluated by means of DFT calculations. Additionally, the Pd-catalyzed C-arylation of the amide unit of selected quinoxalinone derivatives was accomplished.
Das Produkt einer formalen Hydrazidoarylierung von Cyclopentadien konnte erstmals durch Palladium-katalysierte Umsetzung diaza[2.2.1]bicyclischer Alkene mit Arylhalogeniden in Gegenwart von Triphenylarsan, Natriumfluorid und Ameisensäure unter Spaltung einer C-N-Bindung stereoselektiv erhalten werden (siehe Schema).
The product of a formal hydrazidoarylation of cyclopentadiene was obtained for the first time by palladium-catalyzed reaction of diaza[2.2.1]bicyclic alkenes with aryl halides in the presence of triphenylarsane, sodium fluoride, and formic acid under stereoselective cleavage of a CN bond (see scheme).
Epibatidine (1) is a recently discovered trace alkaloid found in the skin of a Latin-American poisonous frog. Its remarkably high analgetic activity is accompanied by high toxicity. Therefore, in order to tune its biological activity, a convergent and efficient synthetic pathway was sought to synthesize epibatidine derivatives with different (het)aryl substituents. The hydro(het)arylation of the key intermediate 7-azabicycloheptene (10) represents such an approach. The synthesis of 10 by a Diels–Alder reaction of an N-activated pyrrole (7) with ethynyl p-tolyl sulfone (6) and subsequent steps has been optimized. The crucial last step, the reductive cleavage of the vinyl sulfone 9, has been replaced by a high-yield fluoride-induced degradation of the β-silylated sulfone 12 to give 10. A number of structurally different racemic epibatidine analogs (16b–e) can be prepared by palladium-catalyzed hydro(het)arylation of 10 with iodo(het)arenes 15b–e in good yields.
1,1′-Binaphthyl derivatives 1-5, substituted in the 2- or 2,2′-positions are used in palladium-catalyzed Suzuki coupling reactions. The mono- and bis-borylated coupling components 2, 4 and 5 can easily be prepared and purified, are air-stable and are therefore interesting starting materials for Suzuki coupling reactions with several aryl halides. Thus a variety of new axially-chiral 2- and 2,2′-arylated 1,1′-binaphthyls can be synthesized. Selective monoarylation of 3, 4 and 5 can be performed. Subsequent and stepwise arylation offers general access to unsymmetrically substituted binaphthyls. Moreover, interesting atropisomeric complex molecules, such as 4,4′-bis[2-(1,1′-binaphthyl)]-1,1′-biphenyl (18a), are accessible. Compounds of type 18, which can be obtained by twofold Pd-catalyzed coupling reactions, are of high potential value as ligands or promoters in catalytic, asymmetric processes or as chiral precursor molecules for host-guest interactions.
