ABSTRACT
Anti-Markovnikov additions to non-conjugated unsaturated amines in superacid are reported. In situ NMR studies, DFT calculations and labelled substrates reactions support the involvement of new ammonium-carbenium superelectrophiles in this original process.
ABSTRACT
A series of benzofused sultams and fluorinated benzenesulfonamides were synthesized in superacid HF/SbF(5) from simple N-allylic derivatives. Almost all of these original compounds showed micromolar inhibitory activities against carbonic anhydrases I and II. The fluorinated derivatives inhibit better the tumor-associated isoforms IX and XII, and one of the tested compounds showed inhibition in the nanomolar range.
Subject(s)
Antimony/chemistry , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrases/chemistry , Fluorides/chemistry , Hydrofluoric Acid/chemistry , Neoplasm Proteins/antagonists & inhibitors , Sulfonamides/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Halogenation , Humans , Isoenzymes/antagonists & inhibitors , Isoenzymes/chemistry , Kinetics , Magnetic Resonance Spectroscopy , Neoplasm Proteins/chemistry , Solutions , Sulfonamides/chemistryABSTRACT
The first direct selective synthesis of novel gem-chlorofluorinated nitrogen-containing building blocks in superacid is reported. The dramatic role of the chlorine atom on the reaction is shown by in situ NMR experiments and allows the involvement of a novel original superelectrophilic activation process in superacid HF/SbF(5) to be postulated.
Subject(s)
Amines/chemical synthesis , Antimony/chemistry , Fluorides/chemistry , Hydrofluoric Acid/chemistry , Amines/chemistry , Molecular Structure , StereoisomerismABSTRACT
The synthesis of benzofused sultams and/or fluorinated sulfonamides, starting from N-allylic sulfonamides, was performed in superacid HF/SbF(5), through superelectrophilic activation. A dramatic effect of superacid composition on the selectivity of the reaction was shown and applied to the synthesis of cyclic 4-aminobenzenesulfonamides.
Subject(s)
Sulfanilamides/chemical synthesis , Antimony/chemistry , Catalysis , Combinatorial Chemistry Techniques , Fluorides/chemistry , Hydrocarbons, Fluorinated/chemical synthesis , Hydrocarbons, Fluorinated/chemistry , Hydrofluoric Acid/chemistry , Molecular Structure , Sulfanilamide , Sulfanilamides/chemistryABSTRACT
This paper describes the scope and limitations of the hydrofluorination reaction in superacid HF/SbF(5). On the basis of experimental studies of polyfunctional substrates' behaviour, the dramatic effect of substitution on the superelectrophilic character of ammonium-carbenium dications was emphasized. This reaction was applied to the synthesis of novel fluorinated key building blocks. Furthermore, the hydrofluorination reaction and the discovered homodimerization/fluorination reaction were applied to the synthesis of highly valued fluorinated diamines.
Subject(s)
Amines/chemistry , Antimony/chemistry , Fluorides/chemistry , Halogenation , Hydrofluoric Acid/chemistry , Cations/chemistry , Dimerization , Nitrogen/chemistryABSTRACT
The novel cyclization/fluorination reaction of N-dienes in superacid was extended to substituted substrates. The influence of the substitution on superelectrophilic character of dicationic intermediates was shown and its dramatic effect on the synthesis of fluoropiperidines was studied. On the basis of new dicationic alpha-chloronium ammonium intermediates, starting from halogen-substituted dienes, high-valued fluorinated piperidines were synthesized.
Subject(s)
Alkenes/chemistry , Antimony/chemistry , Fluorides/chemistry , Halogenation , Hydrofluoric Acid/chemistry , Nitrogen/chemistry , Cyclization , Halogens/chemistry , Piperidines/chemistryABSTRACT
Various N,N-diallylic amines and amides were rapidly converted to fluorinated piperidines after a novel cyclisation/fluorination reaction in superacid HF-SbF5.
Subject(s)
Alkadienes/chemistry , Antimony/chemistry , Fluorides/chemistry , Hydrocarbons, Fluorinated/chemical synthesis , Hydrofluoric Acid/chemistry , Nitrogen/chemistry , Piperidines/chemical synthesis , Crystallography, X-Ray , Cyclization , Hydrocarbons, Fluorinated/chemistry , Models, Molecular , Molecular Structure , Piperidines/chemistry , StereoisomerismABSTRACT
A variety of alkynylated amines, amides, and imides are reacted in the superacid system HF-SbF5 to give regioselectively new beta-gem-difluoroamines. The reaction, which is not observed in pure HF, is consistent with the formation of a dicationic intermediate (i.e., both vinylic and adjacent protonated N-ammonium cations). Application to the regioselective and efficient synthesis of difluorinated cinchona alkaloid derivatives is described.
Subject(s)
Alkynes/chemistry , Antimony/chemistry , Cinchona Alkaloids/chemical synthesis , Fluorides/chemistry , Hydrocarbons, Fluorinated/chemical synthesis , Hydrofluoric Acid/chemistry , Amides/chemistry , Amines/chemistry , Cations/chemistry , Cinchona Alkaloids/chemistry , Crystallography, X-Ray , Halogenation , Hydrocarbons, Fluorinated/chemistry , Imides/chemistry , Models, Molecular , Molecular Structure , StereoisomerismABSTRACT
A range of unsaturated amines and sulfonamides were converted to beta-fluoro nitrogen analogues after hydrofluorination in superacid HF-SbF(5), based on the formation of highly reactive electrophilic intermediates.
