Martin Smrcina

Preparative Separation of Mixtures by Mass Spectrometry

A specially designed mass spectrometer which allows for preparative separation of mixtures is described. This mass spectrometer allows for large ion currents, on the order of nanoamperes, to be produced by electrospray and transmitted into a high vacuum. Accumulation of nanomole quantities of collected and recovered material in several hours is demonstrated. The use of high-velocity ions reduces space charge effects at high ion currents. Separation of mass occurs simultaneously for all ions, providing a 100% duty cycle. The use of a linear dispersion magnet avoids compression at higher m/z ratios. A deceleration lens slows the ions to allow for soft landing at low kinetic energy. The ions are neutralized by ion pairing on an oxidized metal surface. Retractable landing plates allow for easy removal of the separated components.

Selectivity of N- Versus O-Alkylation in Mitsunobu Reactions with Various Quinolinols and Isoquinolinols

Reacting quinolinols and isoquinolinols under Mitsunobu conditions can give rise to N-alkylated products in addition to the normally desired O-alkylated structures. An in-depth study of how the solvent, reagent equivalents, position of the quinoline/isoquinoline nitrogen and type of reacting aliphatic alcohol employed affect the ratio of Nversus O-alkylation is described. The Mitsunobu reaction has been employed within the chemistry community for many years on many scaffolds and has been the subject of multiple reviews. One such scaffold of interest is 2-pyridones (Scheme 1), which are similar to the quinoline and isoquinoline substructure. However, an in-depth study of Nversus O-alkylation of quinolinols and isoquinolinols under Mitsunobu conditions has not been published. Since the Mitsunobu reaction is primarily utilized for O-alkylation, it would be beneficial to understand how altering the reaction conditions can affect the Nor O-alkylation outcome. As with the tautomerism observed in 2-pyridones, quinolinones and isoquinolinones (or quinolinols and isoquinolinols as they will be referred to throughout the paper for clarity) contain the same tautomeric traits as their simplified precursors as shown in Scheme 1. The tautomeric equilibria of 2-hydroxypyridine was shown to depend on solvent polarity, with a pronounced shift to a greater population of the more polar lactam in more polar media. It is this tautomeric equilibria that allows systems of this nature to react as ambident nucleophiles through the conjugate base resonance structures, often leading to mixtures of Oand N-alkylation. However, like with 2-pyridones, we observed that many factors can influence the alkylation ratio. These include, but are not limited to, solvation of the nucleophile (conjugate base of the heterocycle), the electrophilicity of the activated alcohol and the structure of the starting quinolinol or isoquinolinol. HETEROCYCLES, Vol. 94, No. 7, 2017 1305