ACS PRF | ACS
All e-Annual Reports
44697-AC1
Generation, Study, and Application of Dicationic Intermediates
During our study of N-acyliminium ion chemistry, we found examples of a cyclization reaction remarkably similar to the Nazarov reaction. We have found that superacid-catalyzed reactions can lead to a new variation of the Nazarov reaction (eq 1), one that we are calling the aza-Nazarov reaction due to the incorporation of nitrogen into the cyclized product. The results were published recently in Organic Letters. In other N-acyliminium ion investigations, we have found strong evidence for the involvement of dicationic, superelectrophiles. Although the N-acyliminium ion reactions are often done in solutions of high acidity and high temperature, no one has examined the possibility that (some of) these reactions may involve superelectrophiles. 5-Hydroxypyrrolidone (4) reacts with a moderately deactivated arene (p-dichlorobenzene) in trifllic acid (TfOH, Ho –14.1; eq 2). The same reaction in trifluoroacetic acid (TFA, Ho –2.7) gives no arylated product (7). However when an activated arene is used in the reaction with 4 and TFA, the arylated product (8) is obtained (eq 3), indicating that the N-acyliminium ion (5) is generated in the TFA media. This suggests that the superacidic TfOH protosolvates the N-acyliminium ion (5) to produce the superelectrophile (6, eq 2). This study is in press at Chemical Communications. We have also studied the Knorr cyclization, a reaction used to prepare several commercial pharmaceuticals having the quinolin-2-one structure. Most heterocyclic reference books and reviews suggest that the Knorr reaction occurs through an N,O-diprotonated intermediate (9). Using theoretical calculations and spectroscopic methods, we show that the O,O-diprotonated intermediate (10) is the actual intermediate in this reaction. Synthetic studies were also done to show that TfOH is an outstanding catalyst for the reaction (eq 4). This study was submitted recently to the Journal of Organic Chemistry. Another publication citing this PRF grant is a paper entitled, “Superelectrophiles: Charge-Charge Repulsive Effects,” which was submitted recently to Chemistry: A European Journal, as a review article describing our work. We have also found the superacid-catalyzed cyclization of olefins to aza-polycyclic aromatic compounds is extremely efficient (Scheme 1) and it represents an improvement of an earlier reported synthetic route employing alcohol substrates. In related studies, we have found that this chemistry can be used to prepare simple polycyclic aromatic hydrocarbons via monocationic reactions. Other preliminary results have been obtained in studies related to charge migration along alkyl chains. Olefinic pyridines have been prepared and reacted in superacid to produce dicationic intermediates (eqs 6-7). Besides the published and unpublished research studies described above, the success of our research can also be seen in the accomplishments and progress of the students involved in this work. This PRF grant has directly supported the research activities of three graduate students and five undergraduate students. Among the graduate students, two have qualified for their Ph.D. degree. All five undergraduate students have completed their required undergraduate research for their B.S. degrees in chemistry at Northern Illinois University. One of the supported undergraduate students was awarded the Chemistry Department's Undergraduate Research Excellence Award (give to the top student annually) at Northern Illinois University in 2007.
