J Am Chem Soc. 2017 Oct 18;139(41):14352-14355. doi: 10.1021/jacs.7b06813. Epub 2017 Oct 04.

Pomeranz-Fritsch Synthesis of Isoquinoline: Gas-Phase Collisional Activation Opens Additional Reaction Pathways.

Journal of the American Chemical Society

Shibdas Banerjee, Fang Liu, David M Sanchez, Todd J Martínez, Richard N Zare

PMID: 28949532 DOI: 10.1021/jacs.7b06813

Abstract

We have investigated the gas-phase production of isoquinoline by performing collisional activation on benzalaminoacetal, the first intermediate in the classic solution-phase Pomeranz-Fritsch synthesis of isoquinoline. We have elucidated the reaction pathways in the gas phase using tandem mass spectrometry. Unlike the corresponding condensed-phase reaction, where catalytic proton exchange between intermediate(s) and solvent (Brønsted-Lowry base) is known to drive the reaction, the gas-phase reaction follows the "mobile proton model" to form the products via a number of intermediates, some the same as in their condensed-phase counterparts. Energy-resolved mass spectrometry, deuterium labeling experiments, and theoretical calculations (B3LYP/6-31G**) identified 27 different reaction routes in the gas phase, forming a complex interlinked reaction network. The experimental measurements and theoretical calculations confirm the proton hopping onto different basic sites of the precursors and intermediates to transform them ultimately into isoquinoline.

Publication Types

• Journal Article
• Research Support, U.S. Gov't, Non-P.H.S.