Non-conventional Behavior of a 2,1-Benzazaphosphole: Heterodiene or Hidden Phosphinidene?

Invited for the cover of this issue are Zoltán Benkő, Libor Dostál and co-workers at the University of Pardubice and the Budapest University of Technology and Economics. The image depicts signs for the two different pathways representing the two differing reaction types which were clearly observed for 2,1-benzazaphosphole. Read the full text of the article at 10.1002/chem.202101686 .     

Enantioselective analysis of venlafaxine and its active metabolites: A review on the separation methodologies

Venlafaxine (VFX) is a serotonin and norepinephrine reuptake inhibitor chiral drug used in therapy as an antidepressant in the form of a racemate consisting of R‐ and S‐VFX. The two enantiomers of VFX exhibit different pharmacological activities: R‐VFX inhibits both norepinephrine and serotonin synaptic reuptake, whereas S‐VFX inhibits only the serotonin one. R‐ and S‐VFX are metabolized in the liver to the respective R‐ and S‐O‐desmethylvenlafaxine (ODVFX), R‐ and S‐N‐desmethylvenlafaxine (NDVFX), and R‐ and S‐N,O‐didesmethylvenlafaxine (NODVFX). The pharmacological profile of ODVFX is close to that of VFX, whereas the other two chiral metabolites (NDVFX and NODVFX) have lower affinity for the receptor sites. The pharmacokinetics of the VFX enantiomers appear stereoselective, including the metabolism process. In the past 20 years, several studies describing the enantioselective analysis of R‐ and S‐VFX in pharmaceutical formulations and its chiral metabolites in biological matrices were published. These methods encompass liquid chromatography coupled with UV detection, mass spectrometry, or tandem mass spectrometry, and capillary electrophoresis. This paper reviews the published methods used for the determination of the individual enantiomers of VFX and its chiral metabolites in different matrices.     

Hydrogenation of poly(myrcene) and poly(farnesene) using diimide reduction at ambient pressure

Ambient pressure chemical hydrogenation using p-toluene sulfonyl hydrazide (TSH) via thermal diimide formation (N₂H₂) permitted reduction of double bonds of poly(myrcene) (poly[Myr]) and poly(farnesene) (poly[Far]). Both pendent and backbone double bonds in poly(Myr) (M_n = 56 kg/mol) and poly(Far) (M_n = 62 kg/mol) synthesized by conventional free radical polymerization were hydrogenated to almost completion. Furthermore, TSH semi-batch addition efficiently hydrogenated double bonds, while avoiding undesired autohydrogenation of diimides that occurred in batch mode. Thermal stability improved for hydrogenated poly(Myr) and poly(Far), where temperature at 10% weight loss (T_10%) increased from 188 to 404°C for poly(Myr) and from 310 to 379°C for poly(Far). T_gs of poly(Myr) and poly(Far) also increased by about 10–25°C, indicating increased stiffness after hydrogenation. Finally, viscosities of poly(Myr) and poly(Far) were also increased after hydrogenation, and a greater increase was observed for poly(Myr) (by two orders of magnitude from 10² to 10⁴ Pa s) due to its M_n being much higher than its entanglement molecular weight. Poly(Far) viscosity only increased by 1.5 times after hydrogenation (~10⁴ Pa s), comparable to the poly(Myr) after hydrogenation, suggesting unsaturated poly(Far) was more entangled than unsaturated poly(Myr) because of its longer side chains.     

A New Insight into the Stereoelectronic Control of the Pd0-Catalyzed Allylic Substitution: Application for the Synthesis of Multisubstituted Pyran-2-ones via an Unusual 1,3-Transposition

Pyran-2-ones 3 undergo a novel Pd⁰-catalyzed 1,3-rearrangement to afford isomers 6 . The reaction proceeds via an η²-Pd complex, the pyramidalization of which (confirmed by quantum chemistry calculations) offers a favorable antiperiplanar alignment of the Pd−C and allylic C−O bonds ( C ), thus allowing the formation of an η³-Pd intermediate. Subsequent rotation and rate-limiting recombination with the carboxylate arm then gives isomeric pyran-2-ones 6 . The calculated free energies reproduce the observed kinetics semi-quantitatively.     

Reversible C=C Bond Activation by an Intramolecularly Coordinated Antimony(I) Compound

The reaction of N,C,N-chelated stibinidene ArSb ( 1 ) (Ar=C₆H₃-2,6-(CH=NtBu)₂) with selected N-alkyl/aryl-maleimides RN(C(O)CH)₂ (R=Me, tBu, Ph) gave the addition products with bridged bicyclic [2.2.1] structure containing an antimony atom at the bridgehead position, fused with a 6-membered benzene and a 5-membered N-alkyl/aryl-pyrrolidine ring. These compounds were completely characterized. More importantly, additional studies showed that these reactions are reversible in solution, thereby representing an unprecedented reversible activation of a C=C bond by an antimony(I) compound.     

Nitroxide‐Mediated Polymerization of Bio‐Based Farnesene with a Functionalized Methacrylate

Farnesene (Far) is a bio‐based terpene monomer that is similar in structure to commercially used dienes like butadiene and isoprene. Nitroxide‐mediated polymerization (NMP) is adept for the polymerization of dienes, but not particularly effective at controlling the polymerization of methacrylates using commercial nitroxides. In this study, Far is statistically copolymerized with a functional methacrylate, glycidyl methacrylate (GMA), by NMP using N‐succinimidyl modified commercial BlocBuilder (NHS‐BB) initiator. Reactivity ratios are determined to be r _Far = 0.54 ± 0.04 and r _GMA = 0.24 ± 0.02. The ability of the poly(Far‐stat‐GMA) chains to reinitiate for chain extension with styrene showed a clear shift in molecular weight and monomodal distribution. Copolymerizations using a new alkoxyamine, Dispolreg 007 (D7), is explored as it is shown to homopolymerize methacrylates, but not yet reported for statistical copolymerizations. Bimodal molecular weight distributions are observed when an equimolar ratio of Far and GMA is copolymerized with D7 due to slow decomposition of the initiator, but chain ends are active as shown by successful chain extension with styrene. Both NHS‐BB and D7 initiators are used to synthesize poly[Far‐b‐(GMA‐stat‐Far)] and poly(Far‐b‐GMA) diblock copolymers. While the NHS‐BB initiated polymer chains have lower dispersity, D7 exhibits more linear polymerization kinetics and maintains more active chain ends.     

The conformation of epinephrine in polar solvents: an NMR study

Structural Chemistry - Epinephrine (Epi) is a physiologically important catecholamine. Molecular conformation of Epi controls the interactions with other molecules and its biological effects. There...