Cyclization of 2-Acyl- and 2-Thioacylamino-Benzylcyclopropanes in the Gas Phase and Solution

Abstract

Mass spectrometry proved itself to be a powerful tool to predict the directions and yields of mono- molecular reactions of organic compounds. Electron ionization (EI) and electrospray ionization (ESI) were used to study possible transformations of N-(ortho-cyclopropylmethylphenyl)arylamides I and N-(ortho- cyclopropylmethylphenyl)arylthioamides II as well as their para-isomers III and IV in a mass spectrometer and to predict directions and yields of their acid catalyzed cyclization reactions. Several five-eight-membered heterocycles were proposed as possible products of intramolecular transformations of compounds I and II. Reactions of compounds I and II in sulfuric acid solutions were carried out and the results obtained were compared with mass spectrometric data. Surprisingly, EI of the studied compounds mimics their solution reactions better than ESI.

Cyclization of N‐arylcyclopropanecarboxamides into N‐arylpyrrolidin‐2‐ones under electron ionization and in the condensed phase

“…The spectra obtained for several series of ortho ‐substituted cyclopropylbenzenes were used to confirm the presence of the predicted heterocycles in solution. The cyclization products of the molecular ions for these arylcyclopropanes were identical to those synthesized in the condensed phase …”

“…Acid‐catalyzed rearrangement of N ‐arylcyclopropanecarboxamides 1 theoretically could result in the formation of several products including alkenes due to cleavage of the cyclopropyl moiety or heterocyclic compounds formed as a result of ortho ‐substitution in the aromatic ring . However, in all the cases, condensed‐phase transformation of 1 yielded a single product 2 , while some portion of the original reagent remained unreacted.…”

“…This conclusion gives rise to the following question. Why does it not work with this particular group of cyclopropanes, if it worked nicely with other types of cyclopropanes?…”

Mass Spectrometry in Russia

“…25 At the same time, EI mimics solution reactions of 2-acyl-and 2-thioacylaminobenzylcyclopropanes better than ESI. 26 A series of investigations demonstrating the potential of using an EI mass spectrometer as a tool for prognosis of liquid or solid state chemical reactions has been accomplished in IOEC RAS with participation of Yurii Nekrasov. Researchers considered the ionization chamber (IC) of a mass spectrometer as a chemical reactor where bimolecular reactions (not involving ions) can occur, provided the corresponding reactants are introduced in the IC in sufficiently high amounts.…”