Sonia A. Sánchez-Ruiz

Chlorination reactions of ephedrines revisited. Stereochemistry and functional groups effect on the reaction mechanisms

The stereochemistry of the chlorination reactions with SOCl2 of free ephedrine and pseudoephedrine and their hydrochlorides, oxamides and sulfonamides was analyzed. Chlorination of free and hydrochloride erythro isomers occurs with 100% inversion of configuration at C-1 (S N2 mechanism). Chlorination of oxamides and sulfonamides of erythro isomers occurs with retention of the configuration at C-1, (S Ni mechanism). Chlorination reactions in all threo isomers and derivatives hydrochlorides, oxamides or sulfonamides gave the same ratio of erythro (40%) and threo isomers (60%) (SN1 mechanism). Treatment of the isomeric mixture of the chlorodeoxyephedrine and chlorodeoxypseudoephedrine hydrochloride in DMSO with HCl changes the isomeric ratio, increasing the erythro isomer content (65%). Using the erythro ethanolamines it is possible to arrive stereoselectively at the erythro chloroamines if the compound is previously tosylated or converted to the amide, or to the threo chloroamines if the compound is directly chlorinated with SOCl2.

BHδ––δ+HC Interactions inN-Borane andN-Chloroborane Adducts Derived from 1,3,5-Heterocyclohexanes

The molecular structures of 5-methyl-1,3-dithia-5-aziniumcyclohexane iodide, 5-chloroborane-5-methyl-1,3-dithia-5-azacyclohexane, 3,5-bis(borane)-3,5-dimethyl-1-thia-3,5-diazacyclohexane, and 1-borane-1,3,5-trimethyl-1,3,5-triazacyclohexane were determined by X-ray diffraction studies. Interactions between hydridic and protic hydrogen atoms are present when the distances between hydridic and protic hydrogen atoms are shorter than 265 pm and angles for B–N–C bonds are smaller than 107.6(3)°. These interactions explain the conformation of the borane adducts in the solid state.

Structural Analyses of Borane and Chloroborane Adducts of 1,3,5-Dithiaza-, -Dioxaza-, -Thiadiaza-, and -Triazacyclohexanes and Their Rearrangement Products, Boracyclohexanes

Structural and conformational studies performed by 1H-, 11B-, 13C-, two-dimensional, and variable-temperature NMR spectroscopy of borane and chloroborane adducts of 1,3,5-heterocyclohexanes and their rearrangement products, boracyclohexanes, are reported. N-Methyl derivatives gave equatorial N-borane adducts whereas the N-isopropyl derivatives produced the axial borane compounds. Rearrangement reactions of the adducts gave the first examples of chloroboracyclohexanes bearing boron and nitrogen atoms as stable stereogenic centers. BClH2 and BCl2H adducts were found to be more stable towards ring rearrangement than the corresponding N-BH3 analogs.

Stereochemistry of optically active nickel(II) and cobalt(II) coordination compounds derived from N-acetyl aminoalcohols

Herein, we report the stereoselective synthesis and stereochemical analysis of nickel(II) and cobalt(II) coordination compounds derived from N-acetyl-(−)-ephedrine 1(−) and N-acetyl-(+)-ephedrine 1(+), N-acetyl-(+)-pseudoephedrine 2(+) and N-acetyl-(−)-phenylephrine 3(−). Two ligands are coordinated to the metal ion in a tridentate mode giving place to optically active coordination compounds ML2, in a fac octahedral geometry. In all cases, the coordination to the metal ion occurs through the nitrogen atom, the OH group and the deprotonated carboxylic group, forming two five-membered rings. The coordination compounds are characterized in the solid state by UV-Vis-NIR reflectance spectra, IR, X-ray crystallography and magnetic susceptibility measurements. The metal becomes a stereogenic center and, for each ligand, coordination to the metal ion produces two new stereogenic nitrogen and oxygen. Different modes of ligand bonding are present, the fac all-trans, which originates from the fact that the two new stereogenic atoms in each ligand present opposite configurations (mirror effect), as a consequence the bonded ligands are diasteromeric and the complexes have C1 symmetry. The second bonding mode is the fac–cis, which results in the new stereogenic centers acquiring the same configuration; the two bonded ligands are stereochemically identical, producing a complex with C2 symmetry. The use of enantiomeric ligands 1(−) and 1(+) produces separately and stereoselectively the corresponding enantiomeric metallic complexes which are crystallized pure, whereas the use of a racemate of compound 1 produces a different isomer where the metal has a different configuration. Complexes prepared with N-acetyl-ephedrines are diasteromers of those obtained from N-acetyl-pseudoephedrine. The phenylephrine complexes show that the acquired N-configuration is independent of the substitution of the nitrogen vicinal carbon atom and depends only of the cis or trans ligand coordination mode. Analysis of the conformation of the aminoalcohol rings shows that, in all compounds, the phenyl groups are in the equatorial position determining the conformation of the chelates.