Search results for "Aromatic substitution"
showing 10 items of 49 documents
2020
Electrophilic (het)arenes can undergo reactions with nucleophiles yielding π- or Meisenheimer (σ-) complexes or the products of the SNAr addition/elimination reactions. Such building blocks have only rarely been employed for the design of enzyme inhibitors. Herein, we demonstrate the combination of a peptidic recognition sequence with such electrophilic (het)arenes to generate highly active inhibitors of disease-relevant proteases. We further elucidate an unexpected mode of action for the trypanosomal protease rhodesain using NMR spectroscopy and mass spectrometry, enzyme kinetics and various types of simulations. After hydrolysis of an ester function in the recognition sequence of a weakly…
Regioselective substitution of 6,7-dichloroquinoline-5,8-dione: synthesis and X-ray crystal structure of 4a,10,11-triazabenzo[3,2-a]fluorene-5,6-dion…
2003
6,7-Dichloroquinoline-5,8-dione (1) was reacted with a number of 2-aminopyridine derivatives. Of the several possible products of this reaction, 4a,10,11-triazabenzo[3,2-a]fluorene-5,6-dione (6), produced by condensation and rearrangement, was obtained as the major product, and its structure was subsequently unambigously determined by X-ray crystallographic study. Ortho-quinones were produced via nucleophilic substitution at position C7, which was unexpected, considering that para-quinones were produced via C6 substitution in the reaction between compound 1 and ethyl acetoacetate in our previous work. Such unexpected nucleophilic substitution at C7 provides an effective, yet simple route, t…
Unique regioselectivity in the C(sp3)-H α-alkylation of amines: the benzoxazole moiety as a removable directing group.
2014
The benzoxazol-2-yl- substituent was found to act as a removable activating and directing group in the Ir-catalyzed alkylation of C(sp(3))-H bonds adjacent to nitrogen in secondary amines. It can be easily introduced by oxidative coupling or by an SNAr reaction, and it can be removed by hydroxide or by hydride reduction. For 1,2,3,4-tetrahydroisoquinolines, activation exclusively takes place in the 3-position. A variety of activated as well as unactivated terminal olefins are suitable reaction partners.
On the reaction of 3-bromo-2-nitrobenzo[b]thiophene with some ortho-substituted anilines: an analysis of the products of reaction and of their NMR an…
2003
Abstract The title reaction, carried out in DMF in the presence of triethylamine or potassium carbonate, has furnished the ‘expected’ 3-amino-2-nitrobenzo[ b ]thiophenes 2 o together with the ‘unexpected’ 2-amino-3-nitrobenzo[ b ]thiophenes 3 o , thus recalling the situation observed with other weak nucleophiles in the presence of non-nucleophilic bases. The effects (electronic as well as steric) of the ortho -substituent (OH, NH 2 , OMe, Me, Et, F, Cl and Br) on the course of the reaction have been investigated, determining their influence on yields and product ratios ( 2 o / 3 o ). An analysis of 13 C NMR and MS spectra of 2 o and 3 o has been carried out. Ab initio computations on 2 o f …
Ligand Effects on the Chemoselectivity of Ortho-Metalated Rhodium(II) Catalyzed α-Diazo Ketone Transformations
1997
Rh2(OOCR)2(PC)2 complexes (PC = orthometalated phosphines, OOCR = carboxylates) with very polarizable ligands, such as aromatic rings directly joined to the rhodium atoms, control chemoselectivity in competitive metal carbene transformations of α-diazo ketones. These catalysts have a mixed set of ligands that allows choosing among a big selection of ligands to gradually affect the electronic and steric properties of the catalyst. Their selectivity depends on the electrophilicity of the ligands and the polarizability of the metalated aromatic rings. Thus, Rh2(OOCR)2(PC)2 compounds [PC = (C6H4)P(CH3)(C6H5), (p-CH3C6H3)P(p-CH3C6H4)2, (C6H4)P(C6H5)2; R = C3F7 or CF3] exhibit an exceptional sele…
Unveiling the regioselectivity in electrophilic aromatic substitution reactions of deactivated benzenes through molecular electron density theory
2021
The origin of the meta regioselectivity in electrophilic aromatic substitution (EAS) reactions of deactivated benzene derivatives is herein analysed through Molecular Electron Density Theory (MEDT). To this end, the EAS reaction of benzenesulfonic acid with the nitronium NO2+ ion in H2SO4 solution has been studied at the ωB97X-D/6-311G(d,p) level. This reaction takes place through a two-step polar mechanism involving the formation of an unstable cation intermediate. The activation Gibbs free energies associated with the three competitive regioisomeric reaction paths are found in the narrow range of 15.5–18.3 kcal mol−1. By using the Eyring–Polanyi equation a relationship of 18.7 (ortho) : 8…
Aromatic Nucleophilic Substitution (SNAr) of meso-Nitroporphyrin with Azide and Amines as an Alternative Metal Catalyst Free Synthetic Approach To Ob…
2014
International audience; Aromatic nucleophilic substitution reaction of the nitro group of meso-nitroporphyrins with azide and various amines was achieved and represents an alternative procedure to C-N coupling reactions usually needed to obtain such meso-N-substituted porphyrins in good yields.
On the Reaction of 3-Bromo-2-nitrobenzo[b]thiophene 13C-Labeled at C-2 with 3-(Trifluoromethyl)aniline: A Preliminary Insight into a Nucleophilic Su…
1997
The results of the title reaction have furnished proofs against a rearrangement of the carbon-atom skeleton and for a nitro group shift in the relevant nucleophilic substitution.
Asymmetric tandem reactions: New synthetic strategies
2010
The use of domino and multicomponent reactions in asymmetric synthesis is constantly increasing nowadays. This allows for the synthesis of complex molecules in a single synthetic sequence, usually with high atom economy. Herein, we report three examples of new asymmetric tandem reactions recently developed in our laboratories, giving rise to new families of enantiomerically enriched fluorinated and nonfluorinated heterocycles. Thus, 1,4-dihydropyridines (1,4-DHPs) bearing fluorinated substituents at C6 were assembled by means of a Hantzsch-type reaction; cyclic β-amino carbonyl derivatives were prepared using a cross-metathesis (CM)–intramolecular aza-Michael sequence; while fluorinated ind…
Synthesis of new asymmetric xanthene dyes via catalyst-free SNAr with sulfur nucleophiles
2014
Addition of a single functional handle to the tricyclic moiety of fluorescein results in asymmetric xanthene dyes. Our synthesis of a new class of asymmetric xanthenes proceeds via an unusual SNAr with sulfur nucleophiles on electron rich aromatic xanthenes scaffolds in the absence of a metal catalyst. The resulting 3'-thioethers exhibit high photostability and are conveniently converted into reactive dyes for macromolecule labelling.