Aniline | EPFL Graph Search

L’aniline, connue également sous les noms de aminobenzène, phénylamine ou benzèneamine, est un composé organique aromatique de formule chimique . C'est une amine primaire aromatique dérivée du benzène, toxique pour l'homme et l'environnement. Parmi ses dérivés, on compte les chloroanilines, dichloroanilines, trichloroanilines… L'aniline a été, au , à l'origine du développement de l'industrie des colorants de synthèse, regroupés au début sous le nom de Teerfarben (en français « colorants de goudron »). Ces dérivés de l'aniline ont servi pour produire une grande quantité de bleus, violets, mauves et rouges, et quelques noirs, bruns et verts. Historique Otto Unverdorben, distillant de l'indigo, isola en 1826 un produit qu'il appela krystalline. En 1834, Friedlieb Runge parvint à isoler du goudron de houille une substance qui une fois traitée par du chlorure de chaux prend une couleur bleue, qu'il nomma kyanol ou cyanol. En 1841, Carl Julius Fritzsche obtint en traitant de

Synthetic Studies toward Amanita Phalloides Toxins

Philipp Georg Werner Seeberger

Amatoxins are ribosomally synthesized and post-translationally modified bicyclic octapeptides biosynthesized by the deadly basidiomycete fungus Amanita phalloides. Amongst this group, alpha-amanitin is the most widely known toxin and is currently under investigation as part of an antibody-drug conjugate to treat pancreatic cancer. As a consequence, an efficient, modular synthetic route to the molecule is highly desirable. This thesis describes our efforts toward the development of a novel synthesis of alpha-amanitin. An unprecedented tryptathionine formation was envisioned as the key step, which would generate the characteristic cross-linker between cysteine and tryptophan and allow for late stage diversification of the molecule. The transformation would be realized in analogy to a report by Fagnou and co-workers, describing a Rh(III)-catalyzed oxidative annulation of aniline derivatives with internal alkynes to form 2,3-disubstituted indoles. In this effort, several methods for the regioselective formation of 2-substituted indoles were identified in studies with a model thioalkyne. 3,4-Dimethoxybenzyl was chosen as an orthogonal protecting group for the indole nitrogen, and the regioselectivity with respect to substitution on the ring was controlled by exploiting the sterics of the substituent. A method for the selective preparation of 3 sulfenyl indoles was also identified. For several decades, the total synthesis of amanitin had been prevented due to the lack of an efficient method to prepare the characteristic unnatural amino acid dihydroxyisoleucine (DhIle). The present thesis describes a novel, efficient and modular synthesis of this challenging scaffold. The crucial anti-diastereselectivity in the generation of its characteristic stereocenters was obtained in an organocatalyzed asymmetric Mannich reaction/olefination protocol. To avoid lactonization, an alternative synthetic route to a DhIle-containing dipeptide 234 was developed, allowing for the efficient preparation of the valuable diol on a larger scale. Subsequently, preliminary results demonstrated the feasibility of a proposed Pd(II)-catalyzed thioalkynylation by the synthesis of a model dipeptide, and its applicability on a model macrocyclic peptide scaffold was shown. This was later used as a proof of concept for the key Cp*Rh(III)-catalyzed tryptathionine formation. Unfortunately, the isolation of this bicyclic octapeptide was so far unsuccessful, as was the preparation of the target amanitin scaffold. As a consequence, an alternative synthetic strategy to this peptide scaffold was developed. Future works would include its preparation on a larger scale to evaluate the key transformation and access the target alpha-amanitin. The envisioned strategy for the synthesis of alpha-amanitin was also probed for the potential preparation of phalloidin, another potent compound produced by the Death Cap mushroom, with interesting applications as a biological tool. In this effort, a novel synthetic route to a dipeptide containing the characteristic dihydroxyleucine moiety was developed. A route to the cyclic phalloidin scaffold was explored, as well as a potential alternative route to the linear scaffold to allow for efficient scaling of the synthesis.

EPFL2020

Selective Gas Phase Hydrogenation of

Fernando Cardenas Lizana, Rocio Micaela Crespo Quesada, Lioubov Kiwi, Xiaodong Wang

The gas phase (1 atm, 453 K) hydrogenation of p-chloronitrobenzene (p-CNB) over a series of laboratory-synthesized and commercial Pd (1-10% wt) supported on activated carbon (AC) and non-reducible (SiO2 and Al2O3) and reducible (ZnO) oxides has been examined. Reaction over these catalysts generated the target p-chloroaniline (p-CAN) (via selective hydrogenation) and nitrobenzene (NB)/aniline (AN) as a result of a combined hydrodechlorination/hydrogenation. A range of Pd nanoparticles with mean sizes 2.4-12.6 nm (from HRTEM and H-2/CO chemisorption) were generated. Both the p-CNB transformation rate and H-2 chemisorption increased with decreasing Pd size. Residual Mo (from the stabilizer used in the synthesis of Pd colloids) suppressed activity, but this was circumvented by the use of poly(N-vinyl-2-pyrrolidone) (PVP). Pd/AC generated p-CAN and AN as principal products, Pd on SiO2 and Al2O3 exhibited hydrodechlorination character generating AN and NB, and Pd/ZnO promoted the sole formation of p-CAN at all levels of conversion. Reaction selectivity is linked to Pd electron density with the formation of Pd delta+ on AC and the occurrence of Pd delta+ on SiO2 and Al2O3. Reaction exclusivity to p-CAN over Pd/ZnO is attributed to the formation of PdZn alloy (demonstrated by XPS), which selectively activates the -NO2 group. This is the first report that demonstrates 100% selectivity for p-CNB -> p-CAN over supported Pd.

American Chemical Society2013

Mid-Infrared Spectroscopy of Molecular Ions in Helium Nanodroplets

Nils Benedict Brauer, Marcel Drabbels, Xiaohang Zhang

High resolution IR spectra of aniline, styrene and 1,1-diphenylethylene cations embedded in superfluid helium nanodroplets have been recorded in the 300-1700 cm-1 range using the free-electron laser FELIX as radiation source. Comparison of the spectra with available gas phase data reveals that the helium environment induces no significant matrix shift nor leads to an observable line broadening of the resonances. In addition, the IR spectra have provided new and improved vibrational transition frequencies for the cations investigated, as well as for neutral aniline and styrene. Indications have been found that the ions desolvate from the droplets after excitation by a non-evaporative process in which they are ejected from the helium droplets. The kinetic energy of the ejected ions is found to be ion specific and to depend only weakly on the excitation energy.

American Institute of Physics2012

Synthetic Studies toward Amanita Phalloides Toxins

Philipp Georg Werner Seeberger

EPFL2020