A short synthesis of Dronedarone.

A modification of the Nenitzescu reaction was used to obtain Dronedarone from quinonimine 20 and 1,3-diketone 14 (R = CH2CH2CH2NBu2) in a two-stage process in almost 55% overall yield. Our results represent significant improvement over other state-of-the-art methods as no extra steps for the decoration of the benzofuran core are required.

Conformational properties, chiroptical spectra, and molecular self-assembly of 2,3-piperazinodiones and their dithiono analogues.

A family of chiral cyclic oxamides was prepared by the condensation of optically active 1,2-diamines with diethyl oxalate. Thionation of the products with Lawesson's reagent afforded a series of chiral 2,3-piperazinedithiones. Molecular geometries of the title compounds were studied with the use of quantum mechanical DFT calculations and were compared to the X-ray crystallographic results. The heterocyclic six-membered ring adopted a half-chair conformation with the C-5 substituent preferably at the equatorial position, whereas a substitution at the nitrogen atoms resulted in domination of the axial form in the conformational equilibrium. The opposite helicity of the twisted oxamide chromophore in the axial and equatorial conformers led to the opposite signs of the Cotton effects corresponding to two pi-pi* electronic transitions. The CD signs can be predicted by a simple helicity rule. The same rule is valid for 2,3-piperazinodithiones, where a substitution of sulfur for oxygen in the carbonyl groups results in bathochromic shifts of the absorption and CD bands. The crystal packing analysis of several 2,3-piperazinodiones revealed that strong NH...O=C intermolecular hydrogen-bonding interactions generating the chain motif resulted in the formation of 3-D networks as well as with the use of the cyclic hydrogen-bond motif tape structures.

Supramolecular structures of bis-thionooxalamic acid esters derived from (+/-)-cyclohexane-1,2-diamine and (+/-)-1,2-diphenylethylenediamine.

The bis-thionooxalamic acid esters trans-(+/-)-diethyl N,N'-(cyclohexane-1,2-diyl)bis(2-thiooxamate), C14H22N2O4S2, and (+/-)-N,N'-diethyl (1,2-diphenylethane-1,2-diyl)bis(2-thiooxamate), C22H24N2O4S2, both consist of conformationally flexible molecules which adopt similar conformations with approximate C2 rotational symmetry. The thioamide and ester parts of the thiooxamate group are significantly twisted along the central C-C bond, with the S=C-C=O torsion angles in the range 30.94 (19)-44.77 (19) degrees. The twisted s-cis conformation of the thionooxamide groups facilitates assembly of molecules into a one-dimensional polymeric structure via intermolecular three-center C=S...NH...O=C hydrogen bonds and C-H...O interactions formed between molecules of the opposite chirality.